WorldWideScience

Sample records for androgen-insensitivity syndrome

  1. Genetics Home Reference: androgen insensitivity syndrome

    Science.gov (United States)

    ... Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this ... characteristics or signs of both male and female sexual development. Complete androgen insensitivity syndrome occurs when the body ...

  2. Male patients with partial androgen insensitivity syndrome

    DEFF Research Database (Denmark)

    Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm

    2012-01-01

    To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome.......To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome....

  3. Androgen insensitivity syndrome: gonadal androgen receptor activity

    International Nuclear Information System (INIS)

    Coulam, C.B.; Graham, M.L.; Spelsberg, T.C.

    1984-01-01

    To determine whether abnormalities of the androgen receptor previously observed in skin fibroblasts from patients with androgen insensitivity syndrome also occur in the gonads of affected individuals, androgen receptor activity in the gonads of a patient with testicular feminization syndrome was investigated. Using conditions for optimal recovery of androgen receptor from human testes established by previous studies, we detected the presence of a high-affinity (dissociation constant . 3.2 X 10(-10) mol/L), low-capacity (4.2 X 10(-12) mol/mg DNA), androgen-binding protein when tritium-labeled R1881 was incubated at 4 degrees C with nuclear extracts from the gonads of control patients or from a patient with testicular feminization syndrome but not when incubated at 37 degrees C. Thus this patient has an androgen receptor with a temperature lability similar to that of receptors from normal persons

  4. Three siblings with complete androgen insensitivity syndrome

    African Journals Online (AJOL)

    2013-01-13

    Jan 13, 2013 ... male reference range. A diagnosis of complete androgen insensitivity syndrome was made, based on this clinical ... Laboratory test. Value Normal ..... scenario, incomplete resistance may lead to virilisation during puberty.24, ...

  5. Molecular basis of androgen insensitivity

    NARCIS (Netherlands)

    Brinkmann, A.; Jenster, G.; Ris-Stalpers, C.; van der Korput, H.; Brüggenwirth, H.; Boehmer, A.; Trapman, J.

    1996-01-01

    Male sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. In the X-linked androgen insensitivity syndrome, defects in the

  6. Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

    Directory of Open Access Journals (Sweden)

    Sung Won Lee

    2015-06-01

    Full Text Available Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

  7. Role of Imaging in the Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults

    Directory of Open Access Journals (Sweden)

    Marco Nezzo

    2013-01-01

    Full Text Available Complete androgen insensitivity syndrome is an X-linked recessive androgen receptor disorder characterized by a female phenotype with an XY karyotype. Individuals affected by this syndrome have normal female external genitalia but agenesis of the Müllerian duct derivatives, that is, absence of the Fallopian tubes, uterus, cervix, and the proximal part of the vagina, with presence of endoabdominal, labial, or inguinal testes. The estimated prevalence is between 1 and 5 in 100,000 genetic males. Complete androgen insensitivity syndrome can be diagnosed as a result of mismatch between the prenatal sex prediction and the phenotype at birth, can be detected by chance, or remain undetected until investigations for primary amenorrhea. Imaging can be important both to diagnose the pathology and to localize gonads prior to surgical treatment. In this paper, we present three cases of complete androgen insensitivity syndrome in adult women of 34, 22, and 38 years old.

  8. Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Silva Daniela M

    2011-09-01

    Full Text Available Abstract Introduction Androgen is a generic term usually applied to describe a group of sex steroid hormones. Androgens are responsible for male sex differentiation during embryogenesis at the sixth or seventh week of gestation, triggering the development of the testes and penis in male fetuses, and are directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome located on the short arm of chromosome Y. The differentiation of male external genitalia (penis, scrotum and penile urethra occurs between the 9th and 13th weeks of pregnancy and requires adequate concentration of testosterone and the conversion of this to another more potent androgen, dihydrotestosterone, through the action of 5α-reductase in target tissues. Case presentation This report describes the case of a teenage girl presenting with a male karyotype, and aims to determine the extension of the mutation that affected the AR gene. A Caucasian girl aged 15 was referred to our laboratory for genetic testing due to primary amenorrhea. Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome. Conclusions Sex determination and differentiation depend on a cascade of events that begins with the establishment of chromosomal sex at fertilization and ends with sexual maturation at puberty, subsequently leading to fertility. Mutations affecting the AR gene may cause either complete or partial androgen insensitivity syndrome. The case reported here is consistent with complete androgen insensitivity syndrome, misdiagnosed at birth, and consequently our patient was raised both socially and educationally as a female. It is critical that health care providers understand the importance of properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a child with a pseudohermaphrodite phenotype should always undergo adequate

  9. The long-term outcome of boys with partial androgen insensitivity syndrome and a mutation in the androgen receptor gene

    NARCIS (Netherlands)

    Lucas-Herald, A.; S. Bertelloni (Silvano); A. Juul (Anders); J. Bryce (Jillian); Jiang, J.; M. Rodie (Martina); R. Sinnott (Richard); Boroujerdi, M.; Lindhardt Johansen, M.; O. Hiort (Olaf); P-M. Holterhus (Paul-Martin); M.L. Cools (Martine); Guaragna-Filho, G.; Guerra-Junior, G.; N. Weintrob (Naomi); S.E. Hannema (Sabine); S.L.S. Drop (Stenvert); T. Guran (Tulay); F. Darendeliler (Feyza); A. Nordenström (Anna); I.A. Hughes (Ieuan A.); Acerini, C.; Tadokoro-Cuccaro, R.; S.F. Ahmed (Faisal)

    2016-01-01

    textabstractBackground: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term

  10. Complete Androgen Insensitivity Syndrome in Three Sisters

    Directory of Open Access Journals (Sweden)

    Levent Verim

    2014-01-01

    Full Text Available Disorders of sexual development (DSD are congenital anomalies due to atypical development of chromosomes, gonads and anatomy. Complete androgen insensitivity syndrome (CAIS, also known as testicular feminization (TF is a rare DSD disease. The majority of CAIS patients apply to hospital with the complaint of primary amenorrhea or infertility. Given that CAIS patients are all phenotypically female while having 46, XY karyotypes, CAIS diagnosis should be disclosed in an age-appropriate manner preferably by a mental health professional. Cases are reported here for three 46XY siblings consistent with CAIS.

  11. Complete Androgen Insensitivity Syndrome: A Rare Case of Disorder of Sex Development

    Directory of Open Access Journals (Sweden)

    Alfonsa Pizzo

    2013-01-01

    Full Text Available Androgen Insensitivity Syndrome (AIS could be considered as a disease that causes resistance to androgens actions, influencing both the morphogenesis and differentiation of the body structures, and systems in which this hormone exerts its effects. It depends on an X-linked mutations in the Androgen Receptor (AR gene that express a variety of phenotypes ranging from male infertility to completely normal female external genitalia. The clinical phenotypes of AIS could vary and be classified into three categories, as complete (CAIS, partial (PAIS, and mild (MAIS forms, according to the severity of androgen resistance. We will describe a case of CAIS in a 16-year-old patient.

  12. Complete androgen insensitivity syndrome with paratesticular leiomyoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hoon; Oh, Hyung Woo; Lee, Mi Ja; Lim, Dong Hoon [Chosun University College of Medicine, Gwangju (Korea, Republic of)

    2017-03-15

    Complete androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder. Patients with AIS may develop primary amenorrhea due to androgen receptor resistance, resulting in a normal female phenotype and male (XY) karyotype. We report a case of a 30-year-old woman who was diagnosed with complete AIS. Ultrasonography and magnetic resonance imaging revealed bilateral inguinal cryptorchidism and no ovaries and uterus. After gonadectomy, the inguinal mass was confirmed as testicular atrophy with hamartomatous proliferation of Leydig cells and paratesticular leiomyoma. Although these tumors have been reported in association with AIS, this is the first case of paratesticular leiomyoma with hamartomatous proliferation of Leydig cells in atrophic testes being reported in Korea.

  13. Complete androgen insensitivity syndrome with paratesticular leiomyoma: A case report

    International Nuclear Information System (INIS)

    Lee, Ji Hoon; Oh, Hyung Woo; Lee, Mi Ja; Lim, Dong Hoon

    2017-01-01

    Complete androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder. Patients with AIS may develop primary amenorrhea due to androgen receptor resistance, resulting in a normal female phenotype and male (XY) karyotype. We report a case of a 30-year-old woman who was diagnosed with complete AIS. Ultrasonography and magnetic resonance imaging revealed bilateral inguinal cryptorchidism and no ovaries and uterus. After gonadectomy, the inguinal mass was confirmed as testicular atrophy with hamartomatous proliferation of Leydig cells and paratesticular leiomyoma. Although these tumors have been reported in association with AIS, this is the first case of paratesticular leiomyoma with hamartomatous proliferation of Leydig cells in atrophic testes being reported in Korea

  14. AR mutations in 28 patients with androgen insensitivity syndrome (Prader grade 0-3).

    Science.gov (United States)

    Wang, Yi; Gong, Chunxiu; Wang, Xiou; Qin, Miao

    2017-07-01

    We investigated the androgen receptor (AR) gene mutation profiles of Chinese patients exhibiting severe androgen insensitivity syndrome (AIS) phenotypes. The present study enrolled 28 patients with genetically diagnosed AIS, who presented with severe phenotypes (Prader grade 0-3). Patients and some family members were screened via amplification and sequencing of their AR exons 1-8, including the corresponding intronic flanking regions. Luteinizing (LH), follicle-stimulating (FSH), and testosterone (T) hormone levels were found to be slightly, but not significantly, higher in patients with complete androgen insensitivity syndrome (CAIS) than in patients with partial androgen insensitivity syndrome (PAIS) (P>0.05). We identified 24 different AR mutations, including 12 that were novel. Ten patients (cases 2, 3, 10, 28, 11, 12, 19, 20, 24, and 25) were found to carry five recurrent mutations (p.Y572S, p.P914S, p.S176R, p.Y782N, and p.R841H); of these, p.Y572S, p.S176R, and p.Y782N were novel. Among the mutations identified in patients with CAIS, six (66.7%) were characterized as single-nucleotide missense mutations, and six (66.7%) were found to be located in the AR ligand-binding domain (LBD). Among the mutations identified in patients with PAIS, 15 (93.8%) were found to be missense, and 11 (68.8%) were found to be located in the LBD. Patients 10 and 28 were determined to harbor the same missense mutation (p.P914S), but were diagnosed with CAIS and PAIS, respectively. Sex hormone levels were slightly, but not significantly, elevated in patients with CAIS compared to those with PAIS. Missense mutations spanning AR exons 1-8 were the predominant form of identified mutations, and these were mostly located in the AR LBD. Approximately 50% of the identified mutations were novel, and have enriched the AR gene-mutation database. Patients harboring identical mutations were in some instances found to exhibit divergent phenotypes.

  15. The clinical and molecular spectrum of androgen insensitivity syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Hiort, O.; Sinnecker, G.H.G.; Holterhus, P.M.; Nitsche, E.M.; Kruse, K. [Medical Univ. of Luebeck (Germany)

    1996-05-03

    Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic steroids in males leading to defective virilization of the external genitalia. The phenotype encompasses a wide array of genital ambiguity and may range from completely female to undervirilized but unequivocally male with infertility. This disorder is caused by mutations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single nucleotide substitutions within the coding region were detected, each leading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient with spinal and bulbar muscular atrophy, an elongation of a glutamine-repeat was characterized. We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist. 18 refs., 2 figs.

  16. Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor.

    Science.gov (United States)

    Batista, Rafael Loch; Rodrigues, Andresa De Santi; Machado, Aline Zamboni; Nishi, Mirian Yumie; Cunha, Flávia Siqueira; Silva, Rosana Barbosa; Costa, Elaine M F; Mendonca, Berenice B; Domenice, Sorahia

    2018-01-26

    Androgen insensitivity syndrome (AIS) is the most frequent etiology of 46,XY disorders of sex development (DSDs), and it is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. AIS patients present a broad phenotypic spectrum and individuals with a partial phenotype present with different degrees of undervirilized external genitalia. There are more than 500 different AR gene allelic variants reported to be linked to AIS, but the presence of somatic mosaicisms has been rarely identified. In the presence of a wild-type AR gene, a significant degree of spontaneous virilization at puberty can be observed, and it could influence the gender assignment, genetic counseling and the clinical and psychological management of these patients and the psychosexual outcomes of these patients are not known. In this study, we report two patients with AR allelic variants in heterozygous (c.382G>T and c.1769-1G>C) causing a partial AIS (PAIS) phenotype. The first patient was raised as female and she had undergone a gonadectomy at puberty. In both patients there was congruency between gender of rearing and gender identity and gender role. Somatic mosaicism is rare in AIS and nonsense AR variant allelic can cause partial AIS phenotype in this situation. Despite the risk of virilization and prenatal androgen exposure, the gender identity and gender role was concordant with sex of rearing in both cases. A better testosterone response can be expected in male individuals and this should be considered in the clinical management.

  17. A PRACTICAL APPROACH TO THE DETECTION OF ANDROGEN RECEPTOR GENE-MUTATIONS AND PEDIGREE ANALYSIS IN FAMILIES WITH X-LINKED ANDROGEN INSENSITIVITY

    NARCIS (Netherlands)

    RISSTALPERS, C; HOOGENBOEZEM, T; SLEDDENS, HFBM; VERLEUNMOOIJMAN, MCT; DEGENHART, HJ; DROP, SLS; HALLEY, DJJ; Oosterwijk, Jan; HODGINS, MB; TRAPMAN, J; BRINKMANN, AO

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

  18. A practical approach to the detection of androgen receptor gene mutations and pedigree analysis in families with x-linked androgen insensitivity

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Hoogenboezem, T.; Sleddens, H. F.; Verleun-Mooijman, M. C.; Degenhart, H. J.; Drop, S. L.; Halley, D. J.; Oosterwijk, J. C.; Hodgins, M. B.; Trapman, J.

    1994-01-01

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of

  19. Kennedy's disease and partial androgen insensitivity syndrome. Report of 4 cases and literature review.

    Science.gov (United States)

    Valera Yepes, Rocío; Virgili Casas, Maria; Povedano Panades, Monica; Guerrero Gual, Mireia; Villabona Artero, Carles

    2015-05-01

    Kennedy's disease, also known as bulbospinal muscular atrophy, is a rare, X-linked recessive neurodegenerative disorder affecting adult males. It is caused by expansion of an unstable cytosine-adenine-guanine tandem-repeat in exon 1 of the androgen-receptor gene on chromosome Xq11-12, and is characterized by spinal motor neuron progressive degeneration. Endocrinologically, these patients often have the features of hypogonadism associated to the androgen insensitivity syndrome, particularly its partial forms. We report 4 cases with the typical neurological presentation, consisting of slowly progressing generalized muscle weakness with atrophy and bulbar muscle involvement; these patients also had several endocrine manifestations; the most common non-neurological manifestation was gynecomastia. In all cases reported, molecular analysis showed an abnormal cytosine-adenine-guanine triplet repeat expansion in the androgen receptor gene. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  20. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome.

    Science.gov (United States)

    Hines, Melissa; Ahmed, S Faisal; Hughes, Ieuan A

    2003-04-01

    We evaluated psychological outcomes and gender development in 22 women with complete androgen insensitivity syndrome (CAIS). Participants were recruited through a medical database (n = 10) or through a patient support group (n = 12). Controls included 14 males and 33 females, of whom 22 were matched to women with CAIS for age, race, and sex-of-rearing. Outcome measures included quality of life (self-esteem and psychological general well-being), gender-related psychological characteristics (gender identity, sexual orientation, and gender role behavior in childhood and adulthood), marital status, personality traits that show sex differences, and hand preferences. Women recruited through the database versus the support group did not differ systematically, and there were no statistically significant differences between the 22 women with CAIS and the matched controls for any psychological outcome. These findings argue against the need for two X chromosomes or ovaries to determine feminine-typical psychological development in humans and reinforce the important role of the androgen receptor in influencing masculine-typical psychological development. They also suggest that psychological outcomes in women with CAIS are similar to those in other women. However, additional attention to more detailed aspects of psychological well-being in CAIS is needed.

  1. Surface Rendering of External Genitalia of a Fetus at the 32nd Week of Gestation Affected by Partial Androgen Insensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Vincenzo Mazza

    2013-01-01

    Full Text Available Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by 3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the mutation analysis of SRY gene and the 5α-reductase 2 gene (SRD5A2. Results. 3D-4D surface rendering allows the detection of external and internal genital malformations and can address the prenatal diagnosis of PAIS and can exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows an adequate parental counseling and an early optimal management of the condition, not only for the psychological and social reflections but also for the avoidance of complications and postnatal morbidity due to misdiagnosis or delays in the treatment of the genital ambiguity.

  2. Pure seminoma in the setting of androgen insensitivity syndrome treated with surgical resection and para-aortic radiation: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Herman Michael

    2010-01-01

    Full Text Available Complete androgen insensitivity is a rare X-linked disorder characterized by a female phenotype in a chromosomally male individual. Malignant transformation of the un-descended testis is a rare phenomena compared to other inter-sex syndromes. This is a case of a 32-year-old female who was diagnosed with androgen insensitivity and presented to the emergency room with pelvic pain. Later the pelvic pain was found to be due to testicular masses, one of which was pure seminoma. We reviewed the literature emphasizing the biochemical and endocrinologic abnormalities leading to the syndrome, as well as the potential for malignant changes of the un-descended testes, diagnosis, and therapeutic management. We discuss the importance of early diagnosis and the consequence associated with misdiagnosis.

  3. Androgen receptor mutations associated with androgen insensitivity syndrome: a high content analysis approach leading to personalized medicine.

    Directory of Open Access Journals (Sweden)

    Adam T Szafran

    2009-12-01

    Full Text Available Androgen insensitivity syndrome (AIS is a rare disease associated with inactivating mutations of AR that disrupt male sexual differentiation, and cause a spectrum of phenotypic abnormalities having as a common denominator loss of reproductive viability. No established treatment exists for these conditions, however there are sporadic reports of patients (or recapitulated mutations in cell lines that respond to administration of supraphysiologic doses (or pulses of testosterone or synthetic ligands. Here, we utilize a novel high content analysis (HCA approach to study AR function at the single cell level in genital skin fibroblasts (GSF. We discuss in detail findings in GSF from three historical patients with AIS, which include identification of novel mechanisms of AR malfunction, and the potential ability to utilize HCA for personalized treatment of patients affected by this condition.

  4. Bilateral Gonadal Cysts and Late Diagnosis of Androgen Insensitivity Syndrome Treated by Laparoscopic Gonadectomy

    Directory of Open Access Journals (Sweden)

    D. Tourlakis

    2011-01-01

    Full Text Available Background. Complete androgen insensitivity syndrome is a rare syndrome in which the uterus is absent and testes rather than ovaries are present. Patients usually visit a gynecologist due to primary amenorrhea. Case. A forty-eight-year-old woman with lower abdominal pain and anamnesis of uterus agenesis was operated on due to bilateral cystic masses. A 5 × 3 × 1.2 cm left adnexal cyst revealed the presence of a serous cyst with a hypoplastic ductus deferens. A smaller cyst of the right adnexa revealed immature testis tissue with Leydig-cell hyperplasia. After karyotype and hormonal examinations, laparoscopic gonadectomy was performed. Conclusion. Attention should be paid in all cyst-removing operations in cases of uterus agenesis, due to the high incidence of malignancy. Not of less importance is the issue of informing the patient in the most appropriate way.

  5. Tamoxifen treatment for pubertal gynecomastia in two siblings with partial androgen insensitivity syndrome.

    Science.gov (United States)

    Saito, Reiko; Yamamoto, Yukiyo; Goto, Motohide; Araki, Shunsuke; Kubo, Kazuyasu; Kawagoe, Rinko; Kawada, Yasusada; Kusuhara, Koichi; Igarashi, Maki; Fukami, Maki

    2014-01-01

    Although tamoxifen has been shown to be fairly safe and effective for idiopathic pubertal gynecomastia, it remains unknown whether it is also beneficial for gynecomastia associated with endocrine disorders. Here, we report the effect of tamoxifen on pubertal gynecomastia in 2 siblings with partial androgen insensitivity syndrome (PAIS). Cases 1 and 2 presented with persistent pubertal gynecomastia at 13 and 16 years of age, respectively. Physical examinations revealed breast of Tanner stage 3 and normal male-type external genitalia in both cases. Clinical features such as female-type pubic hair and borderline small testis indicated mildly impaired masculinization. Molecular analysis identified a previously reported p.Arg789Ser mutation in the androgen receptor gene (AR) in the 2 cases. Two months of oral administration of tamoxifen ameliorated gynecomastia to Tanner stage 2 with no adverse events. Additional treatment with testosterone enanthate showed negligible effects on body hair and penile length. Hormone values of the 2 cases during tamoxifen treatment remained similar to those in previously reported untreated patients with PAIS. The results indicate that tamoxifen was effective in treating pubertal gynecomastia in these 2 patients with PAIS and may be considered as a therapeutic option in this situation pending further studies.

  6. Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete androgen insensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Felipe P. Andrade

    2012-10-01

    Full Text Available MAIN FINDINGS: A 22-year-old woman with complete androgen insensitivity syndrome (CAIS presenting with primary amenorrhea and normal female external genitalia was referred for laparoscopic gonadectomy. She had been diagnosed several years earlier but was reluctant to undergo surgery. CASE HYPOTHESIS: Diagnosis of this X-linked recessive inherited syndrome characterizes by disturbance of virilization in males with an AR mutation, XY karyotipe, female genitalia and severely undescended testis with risk of malignization. The optimal time to orchidectomy is not settled; neither the real risk of malignancy in these patients. Early surgery impacts development of a complete female phenotype, with enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and surgical technology with single port laparoscopic access we hypothesize that the optimum time for gonadectomy is not at the time of diagnosis, but once feminization has completed. PROMISING FUTURE IMPLICATIONS: An umbilical laparoendoscopic single-site access for bilateral gonadectomy appears to be the first choice approach as leaves no visible incision and diminishes the psychological impact of surgery in a patient with CAIS absolutely reassured as female. KeyPort, a single port access with duo-rotate instruments developed by Richard Wolf facilitates this surgery and allows excellent cosmetic results.

  7. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. J. Genet. ... signal and a C-terminal. Keywords. androgen insensitivity syndrome; androgen receptor; truncation mutation; N-terminal domain; XY sex reversal. .... and an increased risk of gonadal tumour. Mutations in SRY.

  8. Molecular analysis of the androgen-receptor gene in a family with receptor-positive partial androgen insensitivity: an unusual type of intronic mutation

    NARCIS (Netherlands)

    H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); S. Ramnarain; M.C. Verleun-Mooijman; D.P.E. Satijn (David); J. Trapman (Jan); J.A. Grootegoed (Anton); A.O. Brinkmann (Albert)

    1997-01-01

    textabstractIn the coding part and the intron-exon boundaries of the androgen-receptor gene of a patient with partial androgen insensitivity, no mutation was found. The androgen receptor of this patient displayed normal ligand-binding parameters and migrated as a

  9. Androgen insensitivity syndrome

    Science.gov (United States)

    ... the person has some or all of the physical traits of a woman, but the genetic makeup of a man. Causes AIS is caused by genetic defects on the X chromosome. These defects make the body unable to respond to the hormones that produce a male appearance. The syndrome is divided into two main categories: ...

  10. 46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5-Reductase-2 Deficiency, or 17-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes

    Directory of Open Access Journals (Sweden)

    Mazur Tom

    2009-08-01

    Full Text Available Disorders of sex development refer to a collection of congenital conditions in which atypical development of chromosomal, gonadal, or anatomic sex occurs. Studies of 46,XY DSD have focused largely on gender identity, gender role, and sexual orientation. Few studies have focused on other domains, such as physical and mental health, that may contribute to a person's quality of life. The current review focuses on information published since 1955 pertaining to psychological well-being, cognition, general health, fertility, and sexual function in people affected by androgen insensitivity syndromes, 5- reductase-2 deficiency, or 17-hydroxysteroid dehydrogenase-3 deficiency—reared male or female. The complete form of androgen insensitivity syndrome has been the focus of the largest number of investigations in domains other than gender. Despite this, all of the conditions included in the current review are under-studied. Realms identified for further study include psychological well-being, cognitive abilities, general health, fertility, and sexual function. Such investigations would not only improve the quality of life for those affected by DSD but may also provide information for improving physical and mental health in the general population.

  11. Orphan nuclear receptor TLX contributes to androgen insensitivity in castration-resistant prostate cancer via its repression of androgen receptor transcription.

    Science.gov (United States)

    Jia, Lin; Wu, Dinglan; Wang, Yuliang; You, Wenxing; Wang, Zhu; Xiao, Lijia; Cai, Ganhui; Xu, Zhenyu; Zou, Chang; Wang, Fei; Teoh, Jeremy Yuen-Chun; Ng, Chi-Fai; Yu, Shan; Chan, Franky L

    2018-03-20

    The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected. Our previous study shows that the orphan nuclear receptor TLX (NR2E1), which is upregulated in prostate cancer, plays an oncogenic role in prostate carcinogenesis by suppressing oncogene-induced senescence. In the present study, we further established that TLX exhibited an increased expression in metastatic CRPC. Further analyses showed that overexpression of TLX could confer resistance to androgen deprivation and anti-androgen in androgen-dependent prostate cancer cells in vitro and in vivo, whereas knockdown of endogenous TLX could potentiate the sensitivity to androgen deprivation and anti-androgen in prostate cancer cells. Our study revealed that the TLX-induced resistance to androgen deprivation and anti-androgen was mediated through its direct suppression of AR gene transcription and signaling in both androgen-stimulated and -unstimulated prostate cancer cells. We also characterized that TLX could bind directly to AR promoter and repress AR transcription by recruitment of histone modifiers, including HDAC1, HDAC3, and LSD1. Together, our present study shows, for the first time, that TLX can contribute to androgen insensitivity in CRPC via repression of AR gene transcription and signaling, and also implicates that targeting the druggable TLX may have a potential therapeutic significance in CRPC management, particularly in NEPC and PCSCs.

  12. Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series.

    Science.gov (United States)

    Becker, David; Wain, Lisa M; Chong, Yih Harng; Gosai, Sonal J; Henderson, Nina K; Milburn, Jacqui; Stott, Victoria; Wheeler, Benjamin J

    2016-02-01

    X-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty. Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment. Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment. Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone.

  13. Clinical and Laboratorial Features That May Differentiate 46,XY DSD due to Partial Androgen Insensitivity and 5 alpha-Reductase Type 2 Deficiency

    OpenAIRE

    Veiga, NN; Medaets, PAR; Petroli, RJ; Calais, FL; de Mello, MP; Castro, CCTDS; Guaragna, G; Sewaybricker, LE; Marques-de-Faria, AP; Maciel-Guerra, AT; Guerra, G

    2012-01-01

    The aim of this study was to search for clinical and laboratorial data in 46,XY patients with ambiguous genitalia (AG) and normal testosterone (T) synthesis that could help to distinguish partial androgen insensitivity syndrome (PAIS) from 5-reductase type 2 deficiency (5-RD2) and from cases without molecular defects in the AR and SRD5A2 genes. Fifty-eight patients (51 families) were included. Age at first evaluation, weight and height at birth, consanguinity, familial recurrence, severity of...

  14. Spatial memory performance in androgen insensitive male rats.

    Science.gov (United States)

    Jones, Bryan A; Watson, Neil V

    2005-06-02

    Masculinization of the developing rodent brain critically depends on the process of aromatization of circulating testosterone (T) to its estrogenic metabolite 17beta-estradiol, which subsequently interacts with estrogen receptors to permanently masculinize the brain. However, it remains unclear what role other androgenic mechanisms may play in the process of masculinization. A novel way of examining this is through the study of male rats that express the tfm mutation of the androgen receptor (AR) gene; such males are fully androgen insensitive and manifest a female phenotype due to a failure of AR-mediated masculinization of peripheral structures. Because tfm-affected males develop secretory testes and have near-normal T titers during development, aromatization would be expected to proceed normally, and brain mechanisms may be developmentally masculinized despite the feminized periphery. We compared tfm-affected males (X(tfm)Y) with normal males and females in the Morris Water Maze, a task in which males typically perform better than females. Performance of tfm-affected males was intermediate between that of normal males and females. While an overall male superiority was found in the task, the X(tfm)Y group reached male-typical escape latencies faster than females. Furthermore, in the X(tfm)Y group, the granule cell layer of the dentate gyrus was significantly larger than in females. These results support the suggestion that that AR mediated mechanisms contribute to the masculinization of spatial behaviours and hippocampal morphology, and this may be independent of estrogenic processes.

  15. Androgen circle of polycystic ovary syndrome.

    Science.gov (United States)

    Homburg, Roy

    2009-07-01

    Although the aetiology of polycystic ovary syndrome (PCOS) is still not known and the search for causative genes is proving elusive, it is generally agreed that hyperandrogenism is at the heart of the syndrome. Here, it is proposed that excess androgens are the root cause of PCOS starting from their influence on the female fetus in programming gene expression, producing the characteristic signs and symptoms which are then exacerbated by a propagation of excess ovarian androgen production from multiple small follicles, anovulation and insulin resistance in the reproductive life-span, thus setting up a vicious perpetual circle of androgen excess. This opinion paper, rather than being a full-scale review, is intentionally biased in support of this hypothesis that androgen excess is the 'root of all evil' in PCOS; in the hope that its acceptance could lead to more direct treatment of the syndrome in all its facets rather than the symptomatic treatment of side effects of androgen excess that we are addressing today.

  16. Androgen Insensitivity Syndrome in a Family of Warmblood Horses Caused by a 25-bp Deletion of the DNA-Binding Domain of the Androgen Receptor Gene

    DEFF Research Database (Denmark)

    Eastman Welsford, G.; Munk, Rikke; Villagómez, Daniel A.F.

    2017-01-01

    Testicular feminization, an earlier term coined for describing a syndrome resulting from failure of masculinization of target organs by androgen secretions during embryo development, has been well documented not only in humans but also in the domestic horse. The pathology, actually referred...

  17. Androgen Insensitivity Syndrome in a Family of Warmblood Horses Caused by a 25-bp Deletion of the DNA-Binding Domain of the Androgen Receptor Gene

    DEFF Research Database (Denmark)

    Eastman Welsford, G.; Munk, Rikke; Villagómez, Daniel A.F.

    2017-01-01

    Testicular feminization, an earlier term coined for describing a syndrome resulting from failure of masculinization of target organs by androgen secretions during embryo development, has been well documented not only in humans but also in the domestic horse. The pathology, actually referred to as...

  18. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    BALACHANDRAN SARANYA

    with androgen insensitivity syndrome in sex-reversed XY female patients. BALACHANDRAN ..... from the subjects, their family members and controls who participated in the ..... disease, 1st edition. Springer Science + Business Media, New.

  19. Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

    Science.gov (United States)

    Khorashad, Behzad S; Roshan, Ghasem M; Reid, Alistair G; Aghili, Zahra; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; Talaei, Ali; Aarabi, Azadeh; Ghaemi, Nosrat; Taghehchian, Negin; Saberi, Hedieh; Farahi, Nazanin; Abbaszadegan, Mohammad Reza

    2017-01-01

    To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Sexual life and sexual wellness in individuals with complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS).

    Science.gov (United States)

    Fliegner, Maike; Krupp, Kerstin; Brunner, Franziska; Rall, Katharina; Brucker, Sara Y; Briken, Peer; Richter-Appelt, Hertha

    2014-03-01

    Sexual wellness depends on a person's physical and psychological constitution. Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) can compromise sexual well-being. To compare sexual well-being in CAIS and MRKHS using multiple measures: To assess sexual problems and perceived distress. To gain insight into participants' feelings of inadequacy in social and sexual situations, level of self-esteem and depression. To determine how these psychological factors relate to sexual (dys)function. To uncover what participants see as the source of their sexual problems. Data were collected using a paper-and-pencil questionnaire. Eleven individuals with CAIS and 49 with MRKHS with/without neovagina treatment were included. Rates of sexual dysfunctions, overall sexual function, feelings of inadequacy in social and sexual situations, self-esteem and depression scores were calculated. Categorizations were used to identify critical cases. Correlations between psychological variables and sexual function were computed. Sexually active subjects were compared with sexually not active participants. A qualitative content analysis was carried out to explore causes of sexual problems. An extended list of sexual problems based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, by the American Psychiatric Association and related distress. Female Sexual Function Index (FSFI), German Questionnaire on Feelings of Inadequacy in Social and Sexual Situations (FUSS social scale, FUSS sexual scale), Rosenberg Self-Esteem Scale (RSE), Brief Symptom Inventory (BSI) subscale depression. Open question on alleged causes of sexual problems. The results point to a far-reaching lack of sexual confidence and sexual satisfaction in CAIS. In MRKHS apprehension in sexual situations is a source of distress, but sexual problems seem to be more focused on issues of vaginal functioning. MRKHS women report being satisfied with their

  1. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    with androgen insensitivity syndrome in sex-reversed XY female patients. BALACHANDRAN .... Three novel AR gene mutations associated with AIS in XY sex-reversed females. Ta b le. 1 . ( contd. ) ..... disease, 1st edition. Springer Science + ...

  2. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity

    International Nuclear Information System (INIS)

    Lubahn, D.B.; Simental, J.A.; Higgs, H.N.; Wilson, E.M.; French, F.S.; Brown, T.R.; Migeon, C.J.

    1989-01-01

    Androgens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. The authors have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic oligonucleotide primers to bracket coding exons for amplification by the polymerase chain reaction. Genomic DNA was amplified from 46, XY phenotypic female siblings with complete androgen insensitivity syndrome. AR binding affinity for dihydrotestosterone in the affected siblings was lower than in normal males, but the binding capacity was normal. Sequence analysis of amplified exons demonstrated within the AR steroid-binding domain (exon G) a single guanine to adenine mutation, resulting in replacement of valine with methionine at amino acid residue 866. As expected, the carrier mother had both normal and mutant AR genes. Thus, a single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development

  3. Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome?

    Science.gov (United States)

    Corbould, A

    2008-10-01

    Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia in women. The objective was to review evidence for the converse situation, i.e. whether androgens adversely influence insulin action. Androgen excess could potentially contribute to the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in obese peripubertal girls. An Entrez-PubMed search was conducted to identify studies addressing the relationship of androgens with metabolic syndrome/type 2 diabetes in women. Studies reporting outcomes of androgen administration, interventions to reduce androgen effects in hyperandrogenemic women, and basic studies investigating androgen effects on insulin target tissues were reviewed. Multiple studies showed associations between serum testosterone and insulin resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross-sectional nature did not allow conclusions about causality. Androgen administration to healthy women was associated with development of insulin resistance. Intervention studies in women with hyperandrogenism were limited by small subject numbers and use of indirect methods for assessing insulin sensitivity. However, in three of the seven studies using euglycemic hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen action improved insulin sensitivity. Testosterone administration to female rats caused skeletal muscle insulin resistance. Testosterone induced insulin resistance in adipocytes of women in vitro. In conclusion, the metabolic consequences of androgen excess in women have been under-researched. Studies of long-term interventions that lower androgen levels or block androgen effects in young women with hyperandrogenism are needed to determine whether these might protect against metabolic syndrome/type 2 diabetes in later life. Copyright (c) 2008 John Wiley & Sons, Ltd.

  4. Androgens and polycystic ovary syndrome.

    Science.gov (United States)

    Nisenblat, Vicki; Norman, Robert J

    2009-06-01

    Polycystic ovary syndrome (PCOS) is a common complex endocrine genetic disorder, which involves overproduction of androgens, leading to heterogeneous range of symptoms and associated with increased metabolic and cardiovascular morbidity. This review focuses on androgen biosynthesis, use, metabolism in PCOS and clinical consequences of hyperandrogenism. Controversial definition of the disorder and different phenotypic subgroups present a challenge for clinical and basic research. Further investigation of different phenotypes highlights the fact that PCOS probably represents a group of disorders with different etiologies. Prenatal androgen exposure and adolescent studies suggest early in life androgen excess as initiating factor of PCOS, but insufficient evidence available to confirm this hypothesis. Various intracellular signaling pathways implicated in PCOS steroidogenesis and in androgen action have been studied, however, PCOS pathogenesis remains obscure. Growing evidence links androgens with pathophysiology of PCOS and metabolic derangements. Despite intensive investigation, etiology and underlying mechanisms of PCOS remain unclear, warranting further investigation. Better understanding of molecular and genetic basis might lead to invention of novel therapeutic approaches. Long-term interventional studies that lower androgen levels in women with hyperandrogenism might protect against metabolic and cardiovascular comorbidities are needed.

  5. Distributional map of the terminal and sub-terminal sugar residues of the glycoconjugates in the prepubertal and postpubertal testis of a subject affected by complete androgen insensitivity syndrome (Morris's syndrome): lectin histochemical study.

    Science.gov (United States)

    Gheri, G; Vannelli, G B; Marini, M; Zappoli Thyrion, G D; Gheri, R G; Sgambati, E

    2004-01-01

    In the present research we have investigated the distribution of the sugar residues of the glycoconjugates in the prepubertal and postpubertal testes of a subject with Morris's syndrome (CAIS, Complete Androgen Insensitivity Syndrome). For this purpose a battery of six horseradish peroxidase-conjugated lectins was used (SBA, PNA, WGA, ConA, LTA and UEAI). We have obtained a complete distributional map of the terminal and sub-terminal oligosaccharides in the tunica albuginea, interstitial tissue, lamina propria of the seminiferous tubules, Leydig cells, Sertoli cells, spermatogonia, mastocytes and endothelial cells. Furthermore the present study has shown that a large amount of sugar residues were detectable in the prepubertal and postpubertal testes but that some differences exist with particular regard to the Sertoli cells. The Sertoli cells and the Leydig cells of the retained prepubertal testis of the patient affected by Morris's syndrome were characterized by the presence of alpha-L-fucose, which was absent in the retained prepubertal testis of the normal subjects. Comparing the results on the postpubertal testis with those obtained on the same aged testis of healthy subjects we have demonstrated that alpha-L-fucose in the Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the Leydig cells are a unique feature of the subject affected by Morris's syndrome. D-galactose (ss1,3)-N-acetyl-D-galactosamine and sialic acid, which are present in the Leydig cells of the normal testis were never observed in the same cells of the postpubertal testis of the CAIS patient.

  6. Androgen receptor-related diseases: what do we know?

    Science.gov (United States)

    Shukla, G C; Plaga, A R; Shankar, E; Gupta, S

    2016-05-01

    The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages. © 2016 American Society of Andrology and European Academy of Andrology.

  7. Syndrome of achalasia, ACTH insensitivity and alacrima

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosino, M.M.; Genieser, N.B.; Becker, M.H.; Bangaru, B.S.; Sklar, C.

    1986-05-01

    An unusual multisystem disorder characterized by the triad of selective ACTH insensitivity, achalasia and alacrima has recently been described. The following case fulfills the criteria for this syndrome which has not been previously reported in the radiographic literature.

  8. Androgen insensitivity syndrome: Risk of malignancy and timing of surgery in a paediatric and adolescent population

    Directory of Open Access Journals (Sweden)

    Dragan Kravarusic

    2011-01-01

    Full Text Available Background: Management of female phenotype XY disorders poses a series of problems for the treating clinician. Even after a series of investigations and imaging modalities, there are lingering doubts about the exact nature of the disease and the correct management option. Optimal timing and necessity for removal of their testes have been a debated issue by physicians. There is a generally accepted opinion among physicians that the risk of malignancy in androgen insensitivity syndrome (AIS is considerably lower than with other intersex disorders and occurs at a later age. Objective: The highlight of this presentation is to reinforce the value of laparoscopic gonadectomy in management of AIS in correlation with data suggesting higher risk of malignancy. Patients and Methods: A retrospective review of 11 phenotypic females with XY karyotype was carried out. The patients were evaluated by a diagnostic protocol which included clinical, hormonal, sonographic and cytogenetic examinations. Patients/parents were counselled by the team concerning the different treatment modalities and contrary to the assigned gender, laparoscopy was offered to them. Uneventful bilateral gonadectomy was performed in all the patients and gonads submitted for histopathological examination. Results: A total of 11 patients (mean age, 10.4 ΁ 4.1 years, including six with complete AIS and five with partial AIS (PAIS were reviewed. In two patients with PAIS (18.1%, histopathology revealed malignancy (bilateral seminoma and gonadoblastoma and in an additional patient, a benign hamartoma was found. Literature evidence suggests that AIS female phenotype patients retaining their testes through puberty have a 5% chance for developing malignant tumours. Reviewing our results in correlation with literature, we found that PAIS patients may harbour a higher risk of malignancy. Conclusions: In complementation to hormonal tests and cytogenetic techniques, laparoscopic gonadectomy is

  9. Total glucosides of paeony inhibits lipopolysaccharide-induced proliferation, migration and invasion in androgen insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Zhang

    Full Text Available Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP, the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL in the absence or presence of TGP (312.5 μg /mL. As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells. Migration activity, as determined by wound-healing assay and transwell migration assay, and invasion activity, as determined by transwell invasion assay, were elevated in LPS-stimulated PC-3 cells. Interestingly, TGP suppressed LPS-stimulated PC-3 cells proliferation. Moreover, TGP inhibited LPS-stimulated migration and invasion of PC-3 cells. Additional experiment showed that TGP inhibited activation of nuclear factor kappa B (NF-κB and mitogen-activated protein kinase (MAPK/p38 in LPS-stimulated PC-3 cells. Correspondingly, TGP attenuated upregulation of interleukin (IL-6 and IL-8 in LPS-stimulated PC-3 cells. In addition, TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3 in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells.

  10. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome?

    Science.gov (United States)

    Abbott, D H; Barnett, D K; Bruns, C M; Dumesic, D A

    2005-01-01

    The aetiology of polycystic ovary syndrome (PCOS) remains unknown. This familial syndrome is prevalent among reproductive-aged women and its inheritance indicates a dominant regulatory gene with incomplete penetrance. However, promising candidate genes have proven unreliable as markers for the PCOS phenotype. This lack of genetic linkage may represent both extreme heterogeneity of PCOS and difficulty in establishing a universally accepted PCOS diagnosis. Nevertheless, hyperandrogenism is one of the most consistently expressed PCOS traits. Animal models that mimic fetal androgen excess may thus provide unique insight into the origins of the PCOS syndrome. Many female mammals exposed to androgen excess in utero or during early post-natal life typically show masculinized and defeminized behaviour, ovulatory dysfunction and virilized genitalia, although behavioural and ovulatory dysfunction can coexist without virilized genitalia based upon the timing of androgen excess. One animal model shows particular relevance to PCOS: the prenatally androgenized female rhesus monkey. Females exposed to androgen excess early in gestation exhibit hyperandrogenism, oligomenorrhoea and enlarged, polyfollicular ovaries, in addition to LH hypersecretion, impaired embryo development, insulin resistance accompanying abdominal obesity, impaired insulin response to glucose and hyperlipidaemia. Female monkeys exposed to androgen excess late in gestation mimic these programmed changes, except for LH and insulin secretion defects. In utero androgen excess may thus variably perturb multiple organ system programming and thereby provide a single, fetal origin for a heterogeneous adult syndrome.

  11. MicroRNAs related to androgen metabolism and polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Sørensen, Anja Elaine; Udesen, Pernille Bækgaard; Wissing, Marie Louise

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries...

  12. Targets to treat androgen excess in polycystic ovary syndrome.

    Science.gov (United States)

    Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco

    2015-01-01

    The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.

  13. Increased Androgen Response to Follicle-Stimulating Hormone Administration in Women with Polycystic Ovary Syndrome

    OpenAIRE

    Wachs, Deborah S.; Coffler, Mickey S.; Malcom, Pamela J.; Shimasaki, Shunichi; Chang, R. Jeffrey

    2008-01-01

    Context: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production.

  14. Partial androgen insensitivity syndrome

    Science.gov (United States)

    ... being on the underside of the penis, small penis, small scrotum (with a line down the middle or incompletely closed), or undescended testicles . Breast development in males at time of puberty. Decreased body hair and beard, but normal pubic ...

  15. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

    OpenAIRE

    Caldwell, Aimee S. L.; Edwards, Melissa C.; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B.; Handelsman, David J.; Walters, Kirsty A.

    2017-01-01

    The cause of polycystic ovary syndrome (PCOS) is unknown, but androgen excess is a key feature. We combined a hyperandrogenized PCOS mouse model with global and tissue- and cell-specific androgen-resistant mouse lines to uncover the sites of androgen action that initiate PCOS. We demonstrate that direct androgen actions, particularly in neurons but less so in granulosa cells, are required for the development of key reproductive and metabolic PCOS features. These data highlight the previously ...

  16. Effects of orlistat on serum androgen levels among iranian obese women with polycystic ovarian syndrome.

    Science.gov (United States)

    Salehpour, Saghar; Hosseini, Sedighe; Nazari, Leila; Saharkhiz, Nasrin; Zademodarres, Shahrzad

    2018-05-14

    Polycystic ovary syndrome is one of the most common endocrinopathies in young women, and it affects 6% to 8% of women in reproductive age. Hyperandrogenism is the hallmark of polycystic ovary syndrome. The aim of the present study was to evaluate the effects of orlistat on weight loss and serum androgen levels among Iranian women with polycystic ovary syndrome. The present study was carried out in the clinic of Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Thirty-two patients with polycystic ovary syndrome were randomly enrolled. We measured serum androgens (Testosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone and sex hormone-binding globulin) before and after 12 weeks of treatment with orlistat. We used the Rotterdam Criteria for all patients and transvaginal sonography was performed. The mean age of patients was 27.75±6.22 and the mean body mass index was 32.69±0.94 kg/m2. Comparing with baseline, treatment with orlistat resulted in a significant reduction in weight, BMI, and waist circumference (p=0.001). We also found a remarkable reduction in total testosterone levels (p>0.001). Treatment improved the sex hormone-binding globulin plasma levels, but the improvement was not statistically significant. There was no reduction in other androgen levels. This study showed a significant reduction of weight and total testosterone level - the most important androgen in polycystic ovary syndrome - after 12 weeks of treatment with orlistat. Therefore, it seems that a short course of orlistat can be useful in the management of patients with polycystic ovary syndrome.

  17. Androgenic Hormones In Relation To Parameters of the Metabolic Syndrome in male patients

    International Nuclear Information System (INIS)

    Shousha, M. A.; Soliman, S. E.; Semna, S. G.

    2012-12-01

    Back ground and aim of the work :The numerous deleterious effects of metabolic syndrome are being investigated throughout the medical community. Hypo-androgenomes in men is associated with features of the metabolic syndrome, even it may predict the metabolic syndrome, but the association with the metabolic syndrome it self using an accepted definition has not been described. A group 40 men defined as metabolic syndrome were assessed to investigate the relationship between androgenic hormones and parameters of the metabolic syndrome. (Author)

  18. The Point of View of Pathophysiologist-Endocrinologist on the Problem of Age-Related Androgen Deficiency in Men (LOH-Syndrome

    Directory of Open Access Journals (Sweden)

    A.G. Reznikov

    2014-09-01

    Full Text Available The paper presents a pathophysiological analysis of age-related androgen deficiency syndrome in men (LOH-syndrome with special reference to current knowledge of molecular mechanisms of testosterone effects and androgen regulation of the structure and function of organs and systems of the male body. There is emphasized etiological and pathogenetic role of stress in this pathology. There is presented author’s concept of cause-effect relations between chronic stress, metabolic syndrome and LOH-syndrome.

  19. Androgen receptor function links human sexual dimorphism to DNA methylation.

    Directory of Open Access Journals (Sweden)

    Ole Ammerpohl

    Full Text Available Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aberrant androgen receptor function is associated with distinct patterns of DNA-methylation marks in genital tissues. These findings support the concept that transcription factor binding to the DNA has an impact on the shape of the DNA methylome. These data which derived from a rare human model suggest that androgen programming of methylation marks contributes to sexual dimorphism in the human which might have considerable impact on the manifestation of sex-associated phenotypes and diseases.

  20. The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy.

    Science.gov (United States)

    Morote, Juan; Gómez-Caamaño, Antonio; Alvarez-Ossorio, José L; Pesqueira, Daniel; Tabernero, Angel; Gómez Veiga, Francisco; Lorente, José A; Porras, Mariano; Lobato, Juan J; Ribal, María J; Planas, Jacques

    2015-06-01

    Androgen deprivation therapy may promote the development of the metabolic syndrome in patients with prostate cancer. We assessed the prevalence of the full metabolic syndrome and its components during the first year of androgen deprivation therapy. This observational, multicenter, prospective study included 539 patients with prostate cancer scheduled to receive 3-month depot luteinizing hormone-releasing hormone analogs for more than 12 months. Waist circumference, body mass index, lipid profile, blood pressure and fasting glucose were evaluated at baseline and after 6 and 12 months. The metabolic syndrome was assessed according to NCEP ATP III criteria (2001) and 4 other definitions (WHO 1998, AACE 2003, AHA/NHLBI 2005 and IDF 2005). At 6 and 12 months after the initiation of androgen deprivation therapy, significant increases were observed in waist circumference, body mass index, fasting glucose, triglycerides, total cholesterol, and high-density and low-density lipoprotein cholesterol. No significant changes in blood pressure 130/85 or greater were detected. A nonsignificant increase of 3.9% in the prevalence of the full metabolic syndrome (ATP III) was observed (22.9% at baseline vs 25.5% and 26.8% at 6 and 12 months, respectively). The prevalence of the metabolic syndrome at baseline varied according to the definition used, ranging from 9.4% (WHO) to 50% (IDF). At 12 months significant increases in prevalence were observed with the WHO (4.1%) and AHA/NHLBI (8.1%) definitions. Androgen deprivation therapy produces significant early effects on waist circumference, body mass index, fasting glucose, triglycerides and cholesterol. The prevalence of and increase in the metabolic syndrome depend on the defining criteria. Counseling patients on the prevention, early detection and treatment of specific metabolic alterations is recommended. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome.

    Science.gov (United States)

    O'Reilly, Michael W; Kempegowda, Punith; Jenkinson, Carl; Taylor, Angela E; Quanson, Jonathan L; Storbeck, Karl-Heinz; Arlt, Wiebke

    2017-03-01

    Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS. One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four-hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded. As expected, serum concentrations of the classic androgens testosterone (P PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance. We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.

  2. The comparison of free androgen index and serum free testosterone levels in women with hirsutism or polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    M. Metin Yıldırımkaya

    2011-06-01

    Full Text Available In many laboratories free testosterone can not be measured, so that free androgen index is suggested instead. The aim of this study was to compare free androgen index and serum free testosterone levels measured by radioimmunoassay in women with hirsutism or polycystic ovary syndrome.Materials and methods: Totally 94 women referred to the polyclinics of Ankara Numune Hospital were retrospectively included. Three patient groups were composed; 55 of hirsutism, 20 of polycystic ovary syndrome and 19 of both hirsutism and polycystic ovary syndrome. Total testosterone and sex hormone binding globuline levels were measured by chemiluminescence method and free testosterone levels were measured by radioimmunoassay. Free androgen index was calculated from total testosterone and sex hormone binding globuline.Results: There was a significant positive correlation between free testosterone and free androgen index in patients with hirsutism, in patients with polycystic ovary syndrome, in patients with hirsutism and polycystic ovary syndrome, and in total patient group [r(hirsutism=0,597, r(PCOS=0,617, r(hirsutism and PCOS=0,779, r(total patient group=0,649, P<0,01].Receiver operating characteristics curves were drawn to assess the diagnostic power of parameters for all patient groups [For hirsutism (n=55 auROC (FT=0,431 auROC (FAI=0,485] [For PCOS (n=20 auROC (FT=0,431 auROC (FAI=0,359] [For hirsutism and PCOS (n=19 auROC (FT=0,676 auROC (FAI=0,669]. In our study, free testosterone and free androgen index were found useful to diagnose ‘hirsutism and polycystic ovary syndrome’ but not others.Conclusion: Free androgen index can be used instead of free testosterone in hirsutism and polycystic ovary syndrome for diagnosis. J Clin Exp Invest 2011;2(2:152-6

  3. Primary growth hormone insensitivity (Laron syndrome and acquired hypothyroidism: a case report

    Directory of Open Access Journals (Sweden)

    Corneli Ginevra

    2011-07-01

    Full Text Available Abstract Introduction Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. Case presentation We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline. The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. Conclusion The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective

  4. Primary growth hormone insensitivity (Laron syndrome) and acquired hypothyroidism: a case report.

    Science.gov (United States)

    Cotta, Oana R; Santarpia, Libero; Curtò, Lorenzo; Aimaretti, Gianluca; Corneli, Ginevra; Trimarchi, Francesco; Cannavò, Salvatore

    2011-07-11

    Primary growth hormone resistance or growth hormone insensitivity syndrome, also known as Laron syndrome, is a hereditary disease caused by deletions or different types of mutations in the growth hormone receptor gene or by post-receptor defects. This disorder is characterized by a clinical appearance of severe growth hormone deficiency with high levels of circulating growth hormone in contrast to low serum insulin-like growth factor 1 values. We report the case of a 15-year-old Caucasian girl who was diagnosed with Silver-Russell syndrome at the age of four and a half years. Recombinant growth hormone was administered for 18 months without an appropriate increase in growth velocity. At the age of seven years, her serum growth hormone levels were high, and an insulin-like growth factor 1 generation test did not increase insulin-like growth factor 1 levels (baseline insulin-like growth factor 1 levels, 52 μg/L; reference range, 75 μg/L to 365 μg/L; and peak, 76 μg/L and 50 μg/L after 12 and 84 hours, respectively, from baseline). The genetic analysis showed that the patient was homozygous for the R217X mutation in the growth hormone receptor gene, which is characteristic of Laron syndrome. On the basis of these results, the diagnosis of primary growth hormone insensitivity syndrome was made, and recombinant insulin-like growth factor 1 therapy was initiated. The patient's treatment was well tolerated, but unexplained central hypothyroidism occurred at the age of 12.9 years. At the age of 15 years, when the patient's sexual development was almost completed and her menstrual cycle occurred irregularly, her height was 129.8 cm, which is 4.71 standard deviations below the median for normal girls her age. The most important functional tests for the diagnosis of growth hormone insensitivity are the insulin-like growth factor 1 generation test and genetic analysis. Currently, the only effective treatment is daily administration of recombinant insulin-like growth

  5. Role of androgen excess on metabolic aberrations and cardiovascular risk in women with polycystic ovary syndrome.

    Science.gov (United States)

    Christakou, Charikleia D; Diamanti-Kandarakis, Evanthia

    2008-11-01

    Polycystic ovary syndrome (PCOS) is associated with a clustering of metabolic and cardiovascular risk factors. Insulin resistance is implicated as the major player in the metabolic abnormalities and contributes to the increased cardiovascular risk associated with the syndrome. However, androgen excess appears to participate as an independent parameter, which further aggravates the cardiovascular and metabolic aberrations in affected women with PCOS. The resultant impact of hyperandrogenemia possibly acquires clinical significance for women's health in the context of PCOS, particularly since recent data support an increased incidence of coronary artery disease and of cardiovascular events directly related to androgen levels in women with the syndrome.

  6. Cardiometabolic Features of Polycystic Ovary Syndrome: Role of Androgens.

    Science.gov (United States)

    Yanes Cardozo, Licy L; Romero, Damian G; Reckelhoff, Jane F

    2017-09-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects reproductive-age women. Hyperandrogenemia is present in a significant fraction (~80%) of women with PCOS. Increased prevalence of cardiometabolic risk factors is frequently observed in PCOS women. The present review aims to highlight the key role of androgens in mediating the negative cardiometabolic profile observed in PCOS women. Copyright © 2017 the American Physiological Society.

  7. Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

    Directory of Open Access Journals (Sweden)

    De Gendt Karl

    2009-08-01

    Full Text Available Abstract Background Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM. Methods This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs on the Sertoli cells (SCARKO, mice with a ubiquitous loss of androgen ARs (ARKO, hypogonadal (hpg mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO and ARKO (hpg.ARKO mice. Results Microscopic TM was seen in 94% of hpg.ARKO mice (n = 16 and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n = 11 of hpg testes (mean 2 +/- 0.5 per testis and 30% (n = 10 of hpg.SCARKO testes (mean 8 +/- 6 per testis. No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice. Conclusion We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression.

  8. Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome.

    Science.gov (United States)

    Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

    2008-01-01

    Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

  9. Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Gu, Tianwei; Ye, Xiao; Zhu, Dalong; Bi, Yan

    2018-01-01

    Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISI M ); β -cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β -cell dysfunction in women with PCOS.

  10. Androgen deficiency and dry eye syndrome in the aging male.

    Science.gov (United States)

    Azcarate, Patrick M; Venincasa, Vincent D; Feuer, William; Stanczyk, Frank; Schally, Andrew V; Galor, Anat

    2014-07-03

    To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Two hundred sixty-three patients with a mean age of 69 (50-95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95-1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05-0.95) or low (0-0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = -0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  11. Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor.

    Science.gov (United States)

    Patki, Mugdha; Huang, Yanfang; Ratnam, Manohar

    2016-07-22

    It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen-induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co-expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone-independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Ovarian overproduction of androgens

    Science.gov (United States)

    ... the body's testosterone. Tumors of the ovaries and polycystic ovary syndrome (PCOS) can both cause too much androgen production. ... come back after they have been removed. In polycystic ovary syndrome, the following measures can reduce symptoms caused by ...

  13. Implications of the 2014 Androgen Excess and Polycystic Ovary Syndrome Society guidelines on polycystic ovarian morphology for polycystic ovary syndrome diagnosis

    NARCIS (Netherlands)

    Christ, J. P.; Gunning, M. N.; Fauser, B. C.J.M.

    2017-01-01

    The Androgen Excess and Polycystic Ovary Syndrome Society (AEPCOS) has recommended an updated threshold for polycystic ovarian morphology (PCOM) of 25 follicles or more, 10 ml or more of ovarian volume, or both. We describe the effect of these guidelines on reproductive and metabolic characteristics

  14. Genotype and phenotype in Klinefelter syndrome - impact of androgen receptor polymorphism and skewed X inactivation

    DEFF Research Database (Denmark)

    Bojesen, A; Hertz, J M; Gravholt, C H

    2011-01-01

    The phenotypic variation of Klinefelter syndrome (KS) is wide and may by caused by various genetic and epigenetic effects. Skewed inactivation of the supra-numerical X chromosome and polymorphism in the androgen receptor (AR) have been suggested as plausible causes. We wanted to describe X...

  15. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003.

    Science.gov (United States)

    Laron, Zvi

    2004-03-01

    Clinical and laboratory investigations starting in 1958 of a group of dwarfed children resembling isolated GH deficiency but who had very high serum levels of GH led to the description of the syndrome of primary GH resistance or insensitivity (Laron syndrome) and subsequently to the discovery of its molecular defects residing in the GH receptor and leading to an inability of IGF-I generation. With the biosynthesis of IGF-I in 1986, therapeutic trials started. Continuously more and more patients are being diagnosed in many parts of the world with a variety of molecular defects. This syndrome proved to be a unique model that enables the study of the consequences of GH receptor defects, the physiopathology of GH-IGF-I disruption, and comparison of the GH-independent IGF-I effects. This review presents the personal experience gained from the study follow-up and treatment of the 60 patients followed up for many years in the Israeli cohort.

  16. Acne vulgaris: endocriene aspecten

    NARCIS (Netherlands)

    Dekkers, O. M.; Thio, B. H.; Romijn, J. A.; Smit, J. W. A.

    2006-01-01

    Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development

  17. AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome.

    Science.gov (United States)

    O'Reilly, Michael W; Kempegowda, Punith; Walsh, Mark; Taylor, Angela E; Manolopoulos, Konstantinos N; Allwood, J William; Semple, Robert K; Hebenstreit, Daniel; Dunn, Warwick B; Tomlinson, Jeremy W; Arlt, Wiebke

    2017-09-01

    Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. We performed a human deep metabolic in vivo phenotyping study examining the systemic and intra-adipose effects of acute and chronic androgen exposure in 10 PCOS women, in comparison with 10 body mass index-matched healthy controls, complemented by in vitro experiments. PCOS women had increased intra-adipose concentrations of testosterone (P = 0.0006) and dihydrotestosterone (P = 0.01), with increased expression of the androgen-activating enzyme aldo-ketoreductase type 1 C3 (AKR1C3) (P = 0.04) in subcutaneous adipose tissue. Adipose glycerol levels in subcutaneous adipose tissue microdialysate supported in vivo suppression of lipolysis after acute androgen exposure in PCOS (P = 0.04). Mirroring this, nontargeted serum metabolomics revealed prolipogenic effects of androgens in PCOS women only. In vitro studies showed that insulin increased adipose AKR1C3 expression and activity, whereas androgen exposure increased adipocyte de novo lipid synthesis. Pharmacologic AKR1C3 inhibition in vitro decreased de novo lipogenesis. These findings define an intra-adipose mechanism of androgen activation that contributes to adipose remodeling and a systemic lipotoxic metabolome, with intra-adipose androgens driving lipid accumulation and insulin resistance in PCOS. AKR1C3 represents a promising therapeutic target in PCOS. Copyright © 2017 Endocrine Society

  18. Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2012-05-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

  19. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome.

    Science.gov (United States)

    Caldwell, Aimee S L; Edwards, Melissa C; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B; Handelsman, David J; Walters, Kirsty A

    2017-04-18

    Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.

  20. Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

    Science.gov (United States)

    Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Ye, Xiao

    2018-01-01

    Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

  1. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.

    Science.gov (United States)

    Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Abbott, David H

    2005-12-01

    Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

  2. Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

    Science.gov (United States)

    Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

    2008-05-01

    In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

  3. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies.

    Science.gov (United States)

    Xita, Nectaria; Tsatsoulis, Agathocles

    2006-05-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder of premenopausal women, characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance and abdominal obesity as frequent metabolic traits. Although PCOS manifests clinically during adolescence, emerging data suggest that the natural history of PCOS may originate in intrauterine life. Evidence from experimental, clinical, and genetic research supporting the hypothesis for the fetal origins of PCOS has been analyzed. Female primates, exposed in utero to androgen excess, exhibit the phenotypic features of PCOS during adult life. Clinical observations also support a potential fetal origin of PCOS. Women with fetal androgen excess disorders, including congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors, develop features characteristic of PCOS during adulthood despite the normalization of androgen excess after birth. The potential mechanisms of fetal androgen excess leading to a PCOS phenotype in humans are not clearly understood. However, maternal and/or fetal hyperandrogenism can provide a plausible mechanism for fetal programing of PCOS, and this, in part, may be genetically determined. Thus, genetic association studies have indicated that common polymorphic variants of genes determining androgen activity or genes that influence the availability of androgens to target tissues are associated with PCOS and increased androgen levels. These genomic variants may provide the genetic link to prenatal androgenization in human PCOS. Prenatal androgenization of the female fetus induced by genetic and environmental factors, or the interaction of both, may program differentiating target tissues toward the development of PCOS phenotype in adult life.

  4. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

    Science.gov (United States)

    Caldwell, Aimee S. L.; Edwards, Melissa C.; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B.; Walters, Kirsty A.

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS. PMID:28320971

  5. Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Dayanand D. Deo

    2008-01-01

    Full Text Available Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP cells as well as androgen-insensitive (PC-3 and DU-145 cells. At a concentration of 200_nm, LNCaP cells showed a significant increase (20% above control; P<.0001 in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P<.01 to P<.0001 dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

  6. Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect?

    Science.gov (United States)

    Shetelig Løvvik, Tone; Stridsklev, Solhild; Carlsen, Sven M; Salvesen, Øyvind; Vanky, Eszter

    2016-06-01

    Women with polycystic ovary syndrome (PCOS) have increased risk of preterm delivery. Shortening of the cervix is a sign of preterm delivery. This study aimed to investigate potential effect of metformin on cervical length and whether androgen levels correlate with cervical length in PCOS pregnancies. This was a sub-study of a randomized, placebo-controlled, multicenter study (The PregMet study) performed at 11 secondary or tertiary centers from 2005 to 2009. Two-hundred sixty-one pregnancies of 245 women with PCOS, age 18-42 years participated. Participants were randomly assigned to metformin or placebo from first trimester to delivery. We compared cervical length and androgen levels in metformin and placebo groups at gestational weeks 19 and 32. We also explored whether cervical length correlated with androgen levels. We found no difference in cervical length between the metformin and the placebo groups at gestational week 19 and 32. Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group. There were no correlations between androgens and cervical length at week 19. At gestational week 32, androstenedione (P = .02) and DHEAS (P = .03) showed a trend toward negative correlation to cervical length. High androstenedione level correlated with shortening of cervical length from week 19 to 32 when adjusted for confounders (P = .003). T (P = .03), DHEAS (P = .02), and free testosterone index (P = .03) showed a similar trend. Metformin in pregnancy did not affect cervical length in women with PCOS. High maternal androgen levels correlated with cervical shortening from the second to the third trimester of pregnancy, as a sign of cervical ripening.

  7. Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

    Science.gov (United States)

    Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

    2013-06-15

    Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

  8. Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy.

    Science.gov (United States)

    Rezaei, Mohammadali Mohammadzadeh; Rezaei, Mohammadhadi Mohammadzadeh; Ghoreifi, Alireza; Kerigh, Behzad Feyzzadeh

    2016-01-01

    The presence of metabolic syndrome in men with prostate cancer (PCa) undergoing androgen-deprivation therapy (ADT), especially intermittent type, has not been completely evaluated. The aim of this study is to evaluate metabolic syndrome in men with PCa undergoing intermittent ADT. In this longitudinal study, we studied the prevalence of metabolic syndrome and its components in 190 patients who were undergoing intermittent ADT. The metabolic syndrome was defined according to the Adult Treatment Panel III criteria. All metabolic parameters, including lipid profile, blood glucose, blood pressures, and waist circumferences of the patients were measured six and 12 months after treatment. Mean age of the patients was 67.5 ± 6.74 years. The incidence of metabolic syndrome after six and 12 months was 6.8% and 14.7%, respectively. Analysis of various components of the metabolic syndrome revealed that patients had significantly higher overall prevalence of hyperglycemia, abdominal obesity, and hypertriglyceridemia in their six- and 12-month followups, but blood pressure has not been changed in the same period except for diastolic blood pressure after six months. Although there was an increased risk of metabolic syndrome in patients receiving intermittent ADT, it was lower than other studies that treated the same patients with continuous ADT. Also it seems that intermittent ADT has less metabolic complications than continuous ADT and could be used as a safe alternative in patients with advanced and metastatic PCa.

  9. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.

    Science.gov (United States)

    Azziz, Ricardo; Carmina, Enrico; Dewailly, Didier; Diamanti-Kandarakis, Evanthia; Escobar-Morreale, Hector F; Futterweit, Walter; Janssen, Onno E; Legro, Richard S; Norman, Robert J; Taylor, Ann E; Witchel, Selma F

    2006-11-01

    The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. Participants included expert investigators in the field. Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.

  10. Sex Differences in White Matter Microstructure in the Human Brain Predominantly Reflect Differences in Sex Hormone Exposure

    NARCIS (Netherlands)

    van Hemmen, J; Saris, I M J; Cohen-Kettenis, P T; Veltman, D J; Pouwels, P J W; Bakker, J

    Sex differences have been described regarding several aspects of human brain morphology; however, the exact biological mechanisms underlying these differences remain unclear in humans. Women with the complete androgen insensitivity syndrome (CAIS), who lack androgen action in the presence of a 46,XY

  11. Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference?

    Science.gov (United States)

    Liepa, George U; Sengupta, Aditi; Karsies, Danielle

    2008-02-01

    Polycystic ovary syndrome (PCOS) is a condition that involves the excess production of androgens. It affects up to 10% of all American women and can lead to the development of acne, hirsutism, and infertility. It has also been associated with coronary heart disease, diabetes, and metabolic syndrome. Over half of the women who are diagnosed with PCOS are overweight or obese. Recommendations are made for overweight/obese women to lose weight via diet and exercise. Women with PCOS should also consider maintaining a diet that is patterned after the type 2 diabetes diet. This diet includes an increase in fiber and a decrease in refined carbohydrates, as well as a decrease in trans and saturated fats and an increase in omega-3 and omega-9 fatty acids. Foods that contain anti-inflammatory compounds (fiber, omega-3 fatty acids, vitamin E, and red wine) should also be emphasized. Evidence is provided for the impact of these dietary changes on improvements in the androgen profile of PCOS patients.

  12. Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Bingjie Zhang

    2018-01-01

    Full Text Available Women with polycystic ovary syndrome (PCOS show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR and Matsuda insulin sensitivity index (ISIM; β-cell function was assessed by disposition index (DI. We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001. Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434, even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c, plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

  13. The relationship of adrenal androgen level and insulin resistance in polycystic ovary syndrome patients

    International Nuclear Information System (INIS)

    Tan Qingling; Zhang Hui; Chen Biling

    2011-01-01

    Objective: To investigate the relationship between adrenal androgen level and insulin resistance in polycystic ovary syndrome (PCOS) patients. Methods: Twenty-two healthy women and 85 PCOS patients were underwent adrenocorticptropic hormone (ACTH) stimulation test, and 85 PCOS patients were divided into high response-polycystic ovary syndrome (HR-PCOS) group and normal response-polycystic ovary syndrome (NR-PCOS) group. The ratio of serum luteinizing hormone to follicle stimulating hormone (LH/FSH), estradiol (E 2 ), testosterone (T) and progestin (P) were tested by radioimmunoassay method. 17-hydroxy-progesterone (17-OHP), dehydroepiandros-teronesulfate (DHEAS) and androsterone (AD) was tested at 0 and 60 min after an ACTH stimulation test. Body mass index (BMI), waist-to-hip-circumference radio (WHR) and homeostasis modes of assessment for insulin resistence index (HOMA-IR) were also measured. Results: There were 20 cases that 17-OHP levels were higher than normal (HR-PCOS), the other 65 cases were NR-PCOS group. MBI and WHR(MBI: χ 2 =13.874, 14.512, WHR: χ 2 =12.607, 15.153, P all 2 =4.801, 5.326, P all>0.05). HR-PCOS group and NR-PCOS group were significantly higher than the control group for LH/FSH and estradiol (LH/FSH: χ 2 =18.226, 16.327, E2: χ 2 =17.334, 19.261, P all 2 =12.274, P 2 =20.314, 18.492, P all 2 =18.063, 19.214, DHEAS: χ 2 =17.358, 19.355, P all 2 =4.109, 4.362, P all>0.05). AD of HR-PCOS group and NR-PCOS group were higher than control group before and after the ACTH stimulation test (χ 2 =14.062, 16.549, P all 2 =5.541, P>0.05) between the two PCOS groups. Serum cortisol was no difference between HR-PCOS, NR-PCOS and control groups before and after stimulation test. HOMA-IR of HR-PCOS group and NR-PCOS group were higher than control group (χ 2 =19.263, 21.482, P all 2 =13.582, P<0.05). Conclusions: There have significantly higher basal and ACTH-stimulated level of adrenal androgen hyperresponsiveness in PCOS patients. Adrenal androgen

  14. The Role of Androgen Excess in Metabolic Dysfunction in Women : Androgen Excess and Female Metabolic Dysfunction.

    Science.gov (United States)

    Escobar-Morreale, Héctor F

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by the association of androgen excess with chronic oligoovulation and/or polycystic ovarian morphology, yet metabolic disorders and classic and nonclassic cardiovascular risk factors cluster in these women from very early in life. This chapter focuses on the mechanisms underlying the association of PCOS with metabolic dysfunction, focusing on the role of androgen excess on the development of visceral adiposity and adipose tissue dysfunction.

  15. Female adipocyte androgen synthesis and the effects of insulin

    Directory of Open Access Journals (Sweden)

    David Cadagan

    2014-01-01

    Full Text Available The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

  16. Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome.

    Science.gov (United States)

    Bruns, C M; Baum, S T; Colman, R J; Dumesic, D A; Eisner, J R; Jensen, M D; Whigham, L D; Abbott, D H

    2007-10-01

    Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI). To determine whether PA females have altered body fat distribution. Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation. There were no differences in age, weight, BMI or somatometrics. LPA females had approximately 20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (Pandrogenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.

  17. Download this PDF file

    African Journals Online (AJOL)

    on cytogenetic and hormonal diagnostic criteria as well as few sporadic case reports, it was proposed that androgen receptor (AR) defects [i.e. Androgen insensitivity syndrome (AIS), OMIM#300068] might constitute a major etiology within this category. However, this has never been systematically ascertained through an AR ...

  18. Substitution of aspartic acid-686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone-binding characteristics

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Trifiro, M. A.; Kuiper, G. G.; Jenster, G.; Romalo, G.; Sai, T.; van Rooij, H. C.; Kaufman, M.; Rosenfield, R. L.; Liao, S.

    1991-01-01

    We have identified two different single nucleotide alterations in codon 686 (GAC; aspartic acid) in exon 4 of the human androgen receptor gene in three unrelated families with the complete form of androgen insensitivity. One mutation (G----C) results in an aspartic acid----histidine substitution

  19. Testosterone, free testosterone, and free androgen index in women: Reference intervals, biological variation, and diagnostic value in polycystic ovary syndrome

    NARCIS (Netherlands)

    Bui, H.N.; Sluss, P.M.; Hayes, F.J.; Blincko, S.; Knol, D.L.; Blankenstein, M.A.; Heijboer, A.C.

    2015-01-01

    Objective: The objective of our study was to determine reference intervals and biologic variation for testosterone (T), free testosterone (fT), and free androgen index (FAI) in women with accurate methods and to test the discriminative value of these parameters in a polycystic ovary syndrome

  20. A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).

    Science.gov (United States)

    Yamamoto, Hiroyasu; Kouhara, Haruhiko; Iida, Keiji; Chihara, Kazuo; Kasayama, Soji

    2008-04-01

    Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.

  1. Androgen Receptor (AR) Physiological Roles in Male and Female Reproductive Systems: Lessons Learned from AR-Knockout Mice Lacking AR in Selective Cells1

    Science.gov (United States)

    Chang, Chawnshang; Lee, Soo Ok; Wang, Ruey-Sheng; Yeh, Shuyuan; Chang, Ta-Min

    2013-01-01

    ABSTRACT Androgens/androgen receptor (AR) signaling is involved primarily in the development of male-specific phenotypes during embryogenesis, spermatogenesis, sexual behavior, and fertility during adult life. However, this signaling has also been shown to play an important role in development of female reproductive organs and their functions, such as ovarian folliculogenesis, embryonic implantation, and uterine and breast development. The establishment of the testicular feminization (Tfm) mouse model exploiting the X-linked Tfm mutation in mice has been a good in vivo tool for studying the human complete androgen insensitivity syndrome, but this mouse may not be the perfect in vivo model. Mouse models with various cell-specific AR knockout (ARKO) might allow us to study AR roles in individual types of cells in these male and female reproductive systems, although discrepancies are found in results between labs, probably due to using various Cre mice and/or knocking out AR in different AR domains. Nevertheless, no doubt exists that the continuous development of these ARKO mouse models and careful studies will provide information useful for understanding AR roles in reproductive systems of humans and may help us to develop more effective and more specific therapeutic approaches for reproductive system-related diseases. PMID:23782840

  2. The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome.

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Visser, M. de; Kreukels, B.P.; Stijnen, T.; Zandwijken, G.R.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.; Cohen-Kettenis, P.T.

    2010-01-01

    The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (GH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of Ox, at a conventional and low dosage, on behavior, aggression, romantic and sexual interest, mood, and

  3. The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Visser, M.; Kreukels, B.P.C.; Stijnen, T.; Zandwijken, G.R.J.; Keizer-Schrama, S.M.P.F.; Otten, B.J.; Wit, J.M.; Cohen-Kettenis, P.T.

    2010-01-01

    The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (GH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of Ox, at a conventional and low dosage, on behavior, aggression, romantic and sexual interest, mood, and

  4. Establishing the cut off values of androgen markers in the assessment of polycystic ovarian syndrome.

    Science.gov (United States)

    Nadaraja, R N D; Sthaneshwar, P; Razali, N

    2018-04-01

    Hyperandrogenism remains as one of the key features in Polycystic Ovarian Syndrome (PCOS) and can be assessed clinically or determined by biochemical assays. Hirsutism is the most common clinical manifestation of hyperandrogenism. The clinical assessment is subjected to wide variability due to poor interobserver agreement and multiple population factors such as ethnic variation, cosmetic procedures and genetic trait. The difficulty in resolving the androgen excess biochemically is due to a lack of consensus as to which serum androgen should be measured for the diagnosis of PCOS. The aim of the study was to compare and establish the diagnostic cut off value for different androgen biomarker for the diagnosis of PCOS. A total of 312 patients classified to PCOS (n = 164) and non PCOS (n = 148) cohorts were selected from the Laboratory Information System (LIS) based on serum total testosterone (TT) and sex hormone binding globulin (SHBG) from the period of 1st April 2015 to 31st March 2016. PCOS was diagnosed based on Rotterdam criteria. Clinical hyperandrogenism and ultrasound polycystic ovarian morphology were obtained from the clinical records. The other relevant biochemical results such as serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and albumin were also obtained from LIS. Free androgen index (FAI), calculated free testosterone (cFT) and calculated bioavailable testosterone (cBT) were calculated for these patients. Receiver Operating Characteristic (ROC) curve analysis were performed for serum TT, SHBG, FAI, cFT, cBT and LH: FSH ratio to determine the best marker to diagnose PCOS. All the androgen parameters (except SHBG) were significantly higher in PCOS patients than in control (pandrogen indices (FAI, cFT and cBT) showed good correlation with each other. Furthermore, cFT, FAI and calculated BT were shown to be more specific with higher positive likelihood ratio than measured androgen markers. Based on our study, the calculated testosterone

  5. A unique mosaic Turner syndrome patient with androgen receptor gene derived marker chromosome.

    Science.gov (United States)

    Kalkan, Rasime; Özdağ, Nermin; Bundak, Rüveyde; Çirakoğlu, Ayşe; Serakinci, Nedime

    2016-01-01

    Patients with Turner syndrome are generally characterized by having short stature with no secondary sexual characteristics. Some abnormalities, such as webbed neck, renal malformations (>50%) and cardiac defects (10%) are less common. The intelligence of these patients is considered normal. Non-mosaic monosomy X is observed in approximately 45% of postnatal patients with Turner syndrome and the rest of the patients have structural abnormalities or mosaicism involving 46,X,i(Xq), 45,X/46,XX, 45,X and other variants. The phenotype of 45,X/46,X,+mar individuals varies by the genetic continent and degree of the mosaicism. The gene content of the marker chromosome is the most important when correlating the phenotype with the genotype. Here we present an 11-year-old female who was referred for evaluation of her short stature and learning disabilities. Conventional cytogenetic investigation showed a mosaic 45,X/46,X,+mar karyotype. Fluorescence in situ hybridization showed that the marker chromosome originated from the X chromosome within the androgen receptor (AR) and X-inactive specific transcript (XIST) genes. Therefore, it is possible that aberrant activation of the marker chromosome, compromising the AR and XIST genes, may modify the Turner syndrome phenotype.

  6. Finasteride Side Effects and Post-Finasteride Syndrome in Male Androgenic Alopecia

    Directory of Open Access Journals (Sweden)

    Manea Mirela

    2015-10-01

    Full Text Available Finasteride is in present a relatively frequent prescribed drug for male androgenic alopecia. The adverse effects reported by some patients seem to be notable, consisting of various (physical, mental/ neurological, sexual, etc. manifestations which are encountered both during Finasteride administration and after treatment cessation (in the form of `post-Finasteride syndrome`. The pharmacological action and the corresponding adverse effects related to Finasteride administration were investigated and published in literature through several and successive studies. In respect to psychiatric disorders, the most notable concern is related to depressive symptoms and suicidal thoughts among former users of finasteride with persistent adverse effects. Regarding genito-urinary symptoms, these are usually represented by gynecomastia, decreased interest in sexual intercourse/ low level of sexual desire and erectile dysfunction. Finally, we viewed Finasteride side effects and post-Finasteride syndrome as distinct physiopathologic entities, thus requiring possible distinct therapeutic approaches. Additional studies will be necessary, in order to further investigate the cerebral neuromodulation of the two relational (cognitive and sexual functions, both of which may be interfered by administration of hormones or by the corresponding compounds such as Finasteride.

  7. Effects of androgen on immunohistochemical localization of androgen receptor and Connexin 43 in mouse ovary.

    Science.gov (United States)

    Yang, Mei; Li, Jianhua; An, Yulin; Zhang, Shuiwen

    2015-10-01

    Androgens have essential roles in the regulation of follicular development and female fertility. Androgen excess is the leading defect in polycystic ovary syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this study was to elucidate the regarding regulatory role of androgen in the follicular development of female mouse. Immunohistochemical staining and Western blot analyses were performed to detect androgen receptor (AR) and Connexin 43 (Cx43) expression in ovaries from both control and testosterone-treated group mice. In this study, localizations of AR and Cx43 were dramatically altered in testosterone-treated mouse ovaries. In addition, AR expression was significantly increased, whereas Cx43 expression was markedly decreased after testosterone treatment. Alterations of AR and Cx43 expression by testosterone with concomitant reduction of MII oocytes. Overall, these results suggest the involvement of androgen in the regulation of AR and Cx43 localizations in mouse ovary. Alterations of AR and Cx43 expression by testosterone may affect normal folliculogenesis. Together these findings will enable us to begin understanding the important roles of AR and Cx43 actions in the regulation of follicular development, as well as providing insights into the role of AR and Cx43 actions in the androgen-associated reproductive diseases such as PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess: a causative link to polycystic ovarian syndrome.

    Science.gov (United States)

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-10-24

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.

  9. Androgen excess in women: experience with over 1000 consecutive patients.

    Science.gov (United States)

    Azziz, R; Sanchez, L A; Knochenhauer, E S; Moran, C; Lazenby, J; Stephens, K C; Taylor, K; Boots, L R

    2004-02-01

    The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess

  10. Chronic anabolic androgenic steroid usage associated with acute coronary syndrome in bodybuilder

    Directory of Open Access Journals (Sweden)

    Ertan Sonmez

    2016-03-01

    Full Text Available Introduction: It has been argued in current studies that anabolic androgenic steroids (AAS are misused by a great number of bodybuilders and athletes. However, there is diverse and often conflicting scientific data on the cardiac and metabolic complications caused by the misuse of AAS. There may be various reasons for myocardial infarction (MI with normal coronary arteries. However, for the majority of patients, the exact cause is still unknown. Case report: A 32 year-old male who was complaining about severe chest pain was admitted to our emergency department. He had been taking methenolone acetate 200 mg weekly for a period of three years for body building. His cardiac markers were significantly elevated and electrocardiogram (ECG showed peaked T waves in all derivations, which did not show ST elevation or depression. Both right and left coronary artery systems were found to be completely normal as a result of the angiogram. Conclusion: The purpose of this study is to show that AAS induced MI can be encountered with normal coronary arteries during acute coronary syndrome. Keywords: Bodybuilder, Anabolic steroids, Methenolone acetate, Acute coronary syndrome

  11. Growth hormone insensitivity syndrome: A sensitive approach

    Directory of Open Access Journals (Sweden)

    Soumik Goswami

    2012-01-01

    Full Text Available Patients with Growth Hormone Insensitivity have characteristic phenotypic features and severe short stature. The underlying basis are mutations in the growth hormone receptor gene which gives rise to a characteristic hormonal profile. Although a scoring system has been devised for the diagnosis of this disorder, it has not been indisputably validated. The massive expense incurred in the diagnosis and treatment of this condition with suboptimal therapeutic response necessitates a judicious approach in this regard in our country.

  12. Illicit use of androgens and other hormones: recent advances.

    Science.gov (United States)

    Kanayama, Gen; Pope, Harrison G

    2012-06-01

    To summarize recent advances in studies of illicit use of androgens and other hormones. Androgens and other appearance-enhancing and performance-enhancing substances are widely abused worldwide. Three notable clusters of findings have emerged in this field in recent years. First, studies almost unanimously find that androgen users engage in polypharmacy, often ingesting other hormones (e.g., human growth hormone, thyroid hormones, and insulin), ergo/thermogenic drugs (e.g., caffeine, ephedrine, and clenbuterol), and classical drugs of abuse (e.g., cannabis, opiates, and cocaine). Second, reports of long-term psychiatric and medical adverse effects of androgens continue to accumulate. In cardiovascular research particularly, controlled studies have begun to supersede anecdotal evidence, strengthening the case that androgens (possibly acting synergistically with other abused drugs) may cause significant morbidity and even mortality. Third, it is increasingly recognized that androgen use may lead to a dependence syndrome with both psychological and physiological origins. Androgen dependence likely affects some millions of individuals worldwide, and arguably represents the least studied major class of illicit drug dependence. Given mounting evidence of the adverse effects of androgens and associated polypharmacy, this topic will likely represent an expanding area of research and an issue of growing public health concern.

  13. Role of androgen-mediated enhancement of erythropoiesis in the increased body iron stores of patients with polycystic ovary syndrome.

    Science.gov (United States)

    Escobar-Morreale, Héctor F; Luque-Ramírez, Manuel

    2011-04-01

    To determine whether androgen excess contributes to the increased body iron stores of polycystic ovary syndrome (PCOS) by stimulating erythropoietic activity, by measuring serum soluble transferrin receptor (sTfR) concentrations and its ratio to ferritin levels in patients with PCOS, as surrogate markers of erythropoietic activity and of the appropriateness of cellular iron demands for the total body iron contents, respectively. Case-control study. Academic hospital. One hundred-four patients with PCOS and 100 controls without androgen excess. Blood sampling and oral glucose tolerance test. Serum sTfR and ferritin concentrations, as well as indexes of androgen excess, inflammation, obesity, and insulin and glucose metabolism. Serum ferritin levels increased in women presenting with PCOS, obesity, and/or abnormal glucose tolerance, but these disorders did not influence sTfR concentrations. The sTfR/ferritin ratio decreased with obesity and abnormal glucose tolerance, and its logarithm correlated inversely with body mass index, free T, and C-reactive protein levels and directly with the insulin sensitivity and disposition indexes. A stepwise multiple regression analysis indicated that the changes in the insulin sensitivity index explained 7% of the variability of the logarithm of sTfR/ferritin ratio. Increased serum ferritin levels in patients with PCOS are associated with a reduction in insulin sensitivity but do not result from a putative enhancement of erythropoiesis by androgen excess. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Performance of the Androgen Deficiency in Aging Male ...

    African Journals Online (AJOL)

    failure, chronic liver disease, chronic renal failure, tuberculosis, chronic obstructive pulmonary diseases, acquired immunodeficiency syndrome and malignancy. Relevant socio- demographic and diabetes-related information were documented. Clinical evaluation of androgen deficiency. Participants completed the original ...

  15. Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society

    OpenAIRE

    Yildiz, Bulent O.; Azziz, Ricardo

    2009-01-01

    Significant advances have been made in our understanding of ovarian dysfunction in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function are likely to play an important role in its pathophysiology. This review highlights the principal novel concepts presented at the 4th special scientific meeting of the Androgen Excess and PCOS Society, “Ovarian and Adipose Tissue Dysfunction: Potential Roles in Polycystic Ovary Syndrome,” which occurred on June 6, 2008 in San Francisco...

  16. [Psychosexual aspects of intersex syndromes].

    Science.gov (United States)

    Bosinski, H A G

    2006-08-01

    Disorders of somatosexual development that lead to ambiguous genitalia occur in one from 3,000-5,000 newborns. Parents and health care professionals are confronted with a number of crucial questions: to what sex should the child be assigned, what is the appropriate treatment in terms of hormonal and surgical interventions, when and how should these take place, and what impact do they have on the development of gender identity (GI), psychosexual well-being and fertility? This paper reviews the etiology, treatment and outcome in terms of GI and sexual health for the following syndromes: congenital adrenal hyperplasia (CAH), complete and partial androgen insensitivity (cAIS, pAIS), and pure and mixed gonadal dysgenesis (pGD, mGD). Emphasis is focussed on the current discussion involving the timing and extent of genital surgery. Finally, a procedure is introduced that covers the sexual-medical needs of patients, parents and health care professionals.

  17. A new dawn for androgens: Novel lessons from 11-oxygenated C19 steroids.

    Science.gov (United States)

    Pretorius, Elzette; Arlt, Wiebke; Storbeck, Karl-Heinz

    2017-02-05

    The abundant adrenal C19 steroid 11β-hydroxyandrostenedione (11OHA4) has been written off as a dead-end product of adrenal steroidogenesis. However, recent evidence has demonstrated that 11OHA4 is the precursor to the potent androgenic 11-oxygenated steroids, 11-ketotestosterone and 11-ketodihydrotestosterone, that bind and activate the human androgen receptor similarly to testosterone and DHT. The significance of this discovery becomes apparent when considering androgen dependent diseases such as castration resistant prostate cancer and diseases associated with androgen excess, e.g. congenital adrenal hyperplasia and polycystic ovary syndrome. In this review we describe the production and metabolism of 11-oxygenated steroids. We subsequently discuss their androgenic activity and highlight the putative role of these androgens in disease states. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Premature adrenarche: novel lessons from early onset androgen excess.

    Science.gov (United States)

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  19. Androgen insensitivity syndrome: Risk of malignancy and timing of ...

    African Journals Online (AJOL)

    The patients were evaluated by a diagnostic protocol which included clinical, hormonal, sonographic and cytogenetic examinations. Patients/parents were counselled by the team concerning the different treatment modalities and contrary to the assigned gender, laparoscopy was offered to them. Uneventful bilateral ...

  20. Changes in HbA1c and circulating and adipose tissue androgen levels in overweight-obese women with polycystic ovary syndrome in response to electroacupuncture

    DEFF Research Database (Denmark)

    Stener-Victorin, E.; Maliqueo, M.; Soligo, M

    2016-01-01

    AIM: Insulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5 weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS. MATERIAL AND METHODS: Seventeen women ...

  1. Targeting Prostate Cancer with Bifunctional Modulators of the Androgen Receptor

    Science.gov (United States)

    2015-06-01

    Wittmann, B.; Dwyer, M.; Cui, H.; Dye, D.; McDonnell, D.; Norris , J. Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists...Wittmann, B.; Dwyer, M.; Cui, H.; Dye, D.; McDonnell, D.; Norris , J. Inhibition of prostate cancer cell growth by second-site androgen receptor...important clin- ical problem in diseases such as asthma (51, 52), ne- phrotic syndrome (53), and malignancies such as acute lymphoblastic leukemia (54

  2. The relationship between follicular fluid androgen concentrations ...

    African Journals Online (AJOL)

    Polycystic ovary syndrome (PCOS) is the most common cause of oligoanovulation, infertility, and hyperandrogenism in women and characterized by abnormal folliculogenesis. The androgen receptoe ( AR) is present in the ovary in almost all stages of folliculogenesis and has been suggested to play a proliferative role for ...

  3. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys.

    Science.gov (United States)

    Xu, Ning; Kwon, Soonil; Abbott, David H; Geller, David H; Dumesic, Daniel A; Azziz, Ricardo; Guo, Xiuqing; Goodarzi, Mark O

    2011-01-01

    The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD Pexcess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  4. Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test.

    Science.gov (United States)

    Rosenfield, Robert L; Mortensen, Monica; Wroblewski, Kristen; Littlejohn, Elizabeth; Ehrmann, David A

    2011-11-01

    Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A). Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4-7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all. Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671-0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, PPCOS-A, but present in 30% of PCOS-T (P PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese. Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.

  5. Developmental programming by androgen affects the circadian timing system in female mice.

    Science.gov (United States)

    Mereness, Amanda L; Murphy, Zachary C; Sellix, Michael T

    2015-04-01

    Circadian clocks play essential roles in the timing of events in the mammalian hypothalamo-pituitary-ovarian (HPO) axis. The molecular oscillator driving these rhythms has been localized to tissues of the HPO axis. It has been suggested that synchrony among these oscillators is a feature of normal reproductive function. The impact of fertility disorders on clock function and the role of the clock in the etiology of endocrine pathology remain unknown. Polycystic ovarian syndrome (PCOS) is a particularly devastating fertility disorder, affecting 5%-10% of women at childbearing age with features including a polycystic ovary, anovulation, and elevated serum androgen. Approximately 40% of these women have metabolic syndrome, marked by hyperinsulinemia, dyslipidemia, and insulin resistance. It has been suggested that developmental exposure to excess androgen contributes to the etiology of fertility disorders, including PCOS. To better define the role of the timing system in these disorders, we determined the effects of androgen-dependent developmental programming on clock gene expression in tissues of the metabolic and HPO axes. Female PERIOD2::luciferase (PER2::LUC) mice were exposed to androgen (dihydrotestosterone [DHT]) in utero (Days 16-18 of gestation) or for 9-10 wk (DHT pellet) beginning at weaning (pubertal androgen excess [PAE]). As expected, both groups of androgen-treated mice had disrupted estrous cycles. Analysis of PER2::LUC expression in tissue explants revealed that excess androgen produced circadian misalignment via tissue-dependent effects on phase distribution. In vitro treatment with DHT differentially affected the period of PER2::LUC expression in tissue explants and granulosa cells, indicating that androgen has direct and tissue-specific effects on clock gene expression that may account for the effects of developmental programming on the timing system. © 2015 by the Society for the Study of Reproduction, Inc.

  6. Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron Syndrome).

    Science.gov (United States)

    Hershkovitz, Israel; Kornreich, Liora; Laron, Zvi

    2007-10-01

    Comparison between the skeletal remains of Homo floresiensis and the auxological and roentgenological findings in a large Israeli cohort of patients with Laron Syndrome (LS, primary or classical GH insensitivity or resistance) revealed striking morphological similarities, including extremely small stature and reduced cranial volume. LS is an autosomal recessive disease caused by a molecular defect of the Growth Hormone (GH) receptor or in the post-receptor cascades. Epidemiological studies have shown that LS occurs more often in consanguineous families and isolates, and it has been described in several countries in South East Asia. It is our conclusion that the findings from the island of Flores, which were attributed to a new species of the genus Homo, may in fact represent a local, highly inbred, Homo sapiens population in whom a mutation for the GH receptor had occurred. (c) 2007 Wiley-Liss, Inc.

  7. Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Zvi

    2008-03-01

    Laron syndrome (LS, congenital primary GH insensitivity) is caused by deletions or mutations in the GH receptor gene, resulting in an inability to generate insulin-like growth factor-I (IGF-I). If untreated, the deficiency of IGF-I results in severe dwarfism, as well as skeletal and muscular underdevelopment. The only treatment is the daily administration of recombinant IGF-I. This review summarizes the present experience by several groups worldwide. The main conclusions are: A. The one or two injections regimen result in the same growth velocity; B. The growth velocity obtained with IGF-I administration is smaller than that observed with hGH in children with congenital isolated GH deficiency; C. Overdosage of IGF-I causes a series of adverse effects which can be avoided by carefully monitoring the serum IGF-I and GH levels.

  8. Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

    Directory of Open Access Journals (Sweden)

    Sotiria Palimeri

    2016-06-01

    Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen exposure, exert a more profound negative impact on the kidney of an androgenized female rat model that mimics the metabolic characteristics of polycystic ovary syndrome.

  9. The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer H. Gunter

    2012-01-01

    Full Text Available An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

  10. The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

    Science.gov (United States)

    Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

    2012-01-01

    An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer. PMID:22548055

  11. Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity).

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Lilos, Pearl; Arbiv, Mira; Vaisman, Nahum

    2006-07-01

    To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. Lifelong congenital IGF-I deficiency leads to extreme adiposity.

  12. Anti-Androgenic Activity of Nardostachys jatamansi DC and Tribulus terrestris L. and Their Beneficial Effects on Polycystic Ovary Syndrome-Induced Rat Models.

    Science.gov (United States)

    Sandeep, Palakkil Mavilavalappil; Bovee, Toine F H; Sreejith, Krishnan

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a major hyperandrogenic disorder. Many drugs prescribed specifically to treat PCOS have side effects; however, previous studies suggest that natural therapeutics including botanicals may be less invasive and equally effective for the management of PCOS. In the present study, plants were screened for antiandrogenic activity using the RIKILT yeast Androgen bioAssay (RAA). Selected positive plants were subsequently tested for their efficacy against PCOS induced by estradiol valerate (EV) in rat models. RAA revealed the antiandrogenic property of Nardostachys jatamansi DC (NJ), Tribulus terrestris L. (TT), and Embelia tsjeriam-cottam DC (EJ), whereas Whithania somnifera Dunal (WS), Symplocos racemosa Roxb. (SR), and Helicteres isora L. (HI) exhibited androgenic properties. EJ also exhibited mild androgenic activity and therefore was excluded from further study. EV administration reduced the weight gain and disrupted cyclicity in all rats. NJ and TT extract treatment normalized estrous cyclicity and steroidal hormonal levels and regularized ovarian follicular growth. The in vitro antiandrogenic activity of plant extracts and their positive effects on different parameters of PCOS were proved in vivo.

  13. Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival.

    Directory of Open Access Journals (Sweden)

    Audrey Dayon

    Full Text Available BACKGROUND: Sphingosine kinase-1 (SphK1 is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a

  14. Free androgen index and Irisin in polycystic ovary syndrome.

    Science.gov (United States)

    Li, H; Xu, X; Wang, X; Liao, X; Li, L; Yang, G; Gao, L

    2016-05-01

    PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects. 166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays. PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI. The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

  15. An Update on Plant Derived Anti-Androgens

    Science.gov (United States)

    Grant, Paul; Ramasamy, Shamin

    2012-01-01

    Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials. PMID:23843810

  16. Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society.

    Science.gov (United States)

    Yildiz, Bulent O; Azziz, Ricardo

    2010-07-01

    Significant advances have been made in our understanding of ovarian dysfunction in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function are likely to play an important role in its pathophysiology. This review highlights the principal novel concepts presented at the 4th special scientific meeting of the Androgen Excess and PCOS Society, "Ovarian and Adipose Tissue Dysfunction: Potential Roles in Polycystic Ovary Syndrome," which occurred on June 6, 2008 in San Francisco, California. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  18. Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome

    OpenAIRE

    Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

    2008-01-01

    Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of DHEAS, typical of PCOS women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in co...

  19. Partial androgen deficiency, depression and testosterone treatment in aging men.

    Science.gov (United States)

    Amore, Mario; Scarlatti, Fabiano; Quarta, Antonio Lucio; Tagariello, Pietro

    2009-02-01

    This study provides a critical review of the literature on depressive symptoms of partial androgen deficiency (PADAM) and their treatment with Testosterone (T). PADAM in aging males is responsible for a variety of behavioral symptoms, such as weakness, decreased libido and erectile dysfunction, lower psychological vitality, depressive mood, anxiety, insomnia, difficulty in concentrating, and memory impairment. The psychological and behavioural aspects of PADAM may overlap with signs and symptoms of major depression. Evidence of the relationship between androgen deficiency and male depression comes from studies that have assessed depression in hypogonadal subjects, the association between low T level and male depressive illness, and the antidepressant action of androgen replacement. The etiology of depressive symptoms of PADAM is multifactorial, and results from the interaction of the biological and psychosocial changes that take place during the mid-life transition. Although data derived from androgen treatment trials and androgen replacement do not support T treatment or replacement as more efficacious than placebo for major depressive disorder (MDD), the clinical impression is that, in some sub-threshold depressive syndromes, T may lead to antidepressant benefits.

  20. Excess androgen during puberty disrupts circadian organization in female rats.

    Science.gov (United States)

    Sellix, Michael T; Murphy, Zachary C; Menaker, Michael

    2013-04-01

    Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.

  1. Androgen excess: Investigations and management.

    Science.gov (United States)

    Lizneva, Daria; Gavrilova-Jordan, Larisa; Walker, Walidah; Azziz, Ricardo

    2016-11-01

    Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. Copyright © 2016. Published by Elsevier Ltd.

  2. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics. SHUWU QI. Articles written in Journal of Genetics. Volume 96 Issue 4 September 2017 pp 695-700 RESEARCH NOTE. Clinical and genetic characterization of six cases with complete androgen insensitivity syndrome in China · JING HE SHUWU QI HUIJUN ZHANG JINGJING GUO ...

  3. Origin of Androgen-Insensitive Poorly Differentiated Tumors in the Transgenic Adenocarcinoma of Mouse Prostate Model

    Directory of Open Access Journals (Sweden)

    Wendy J. Huss

    2007-11-01

    Full Text Available Following castration, the transgenic adenocarcinoma of mouse prostate (TRAMP model demonstrates rapid development of SV40-Tag-driven poorly differentiated tumors that express neuroendocrine cell markers. The cell population dynamics within the prostates of castrated TRAMP mice were characterized by analyzing the incorporation of 5-bromodeoxyuridine (BrdUrd and the expression of SV40-Tag, synaptophysin, and androgen receptor (AR. Fourteen days postcastration, the remaining epithelial cells and adenocarcinoma cells were nonproliferative and lacked detectable SV40-Tag or synaptophysin expression. In contrast, morphologically distinct intraglandular foci were identified which expressed SV40-Tag, synaptophysin, and Ki67, but that lacked AR expression. These proliferative SV40-Tag and synaptophysin-expressing intraglandular foci were associated with the rare BrdUrd-retaining cells. These foci expanded rapidly in the postcastration prostate environment, in contrast to the AR- and SV40-Tag-expressing adenocarcinoma cells that lost SV40-Tag expression and underwent apoptosis after castration. Intraglandular foci of synaptophysin-expressing cells were also observed in the prostates of intact TRAMP mice at a comparable frequency; however, they did not progress to rapidly expanding tumors until much later in the life of the mice. This suggests that the foci of neuroendocrine-like cells that express SV40-Tag and synaptophysin, but lack AR, arise independent of androgen-deprivation and represent the source of the poorly differentiated tumors that are the lethal phenotype in the TRAMP model.

  4. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    Science.gov (United States)

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  5. Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess: a prospective study.

    Science.gov (United States)

    Yuan, Chun; Liu, Xiaoqiang; Mao, Yundong; Diao, Feiyang; Cui, Yugui; Liu, Jiayin

    2016-05-01

    Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome (PCOS). There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index (BMI), total testosterone (TT), modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin (SHBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index (FAI) between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyperandrogenism had significantly higher BMI (P PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong predictor of hyperandrogenism in PCOS. © 2016 the Journal of Biomedical Research. All rights reserved.

  6. Autistic Traits in Women with Polycystic Ovary Syndrome

    Science.gov (United States)

    Herguner, Sabri; Harmanci, Hatice; Hergner, Arzu; Toy, Harun

    2012-01-01

    Several studies suggested that prenatal androgen exposure might contribute to development of polycystic ovary syndrome (PCOS). The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone levels. Furthermore, higher rates of androgen-related conditions including PCOS are reported in…

  7. In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

    Directory of Open Access Journals (Sweden)

    Alison K. Heather

    2013-02-01

    Full Text Available Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping.

  8. Association of clinical androgen excess with radial artery intima media thickness in women with polycystic ovary syndrome.

    Science.gov (United States)

    Yilmaz, S A; Kebapcilar, A; Koplay, M; Kerimoglu, O S; Pekin, A T; Gencoglu, B; Dogan, N U; Celik, C

    2015-06-01

    This study explores the relationship between clinical cardiovascular risk factors and clinical androgen excess, with direct comparison to radial artery intima media thickness (rIMT). rIMT of 91 patients with polycystic ovary syndrome (PCOS) were compared with 72 healthy women. Patients were divided into three groups with regard to body mass index (BMI). Group1 = 56 women (31 controls and 25 PCOS) with low BMI(18-22.49 kg/m(2)), Group2 = 36 women (15 controls and 21 PCOS) with normal BMI (22.5-24.99 kg/m(2)) and Group3 = 71 women (26 controls and 45 PCOS) with high BMI (25-30 kg/m(2)). rIMT was significantly higher in patients with PCOS (p = 0.007). rIMT was significantly higher group1 and group3 in patients with PCOS compared to controls (p = 0.007 and p = 0.042, respectively). There was a significant positive association between rIMT levels and fT in women with PCOS in group1 (r = 0.24, p = 0.04). rIMT levels correlated to fT levels in women with PCOS in group3 (r = 0.32, p = 0.03). Modified Ferriman-Gallwey (mFG) scores demonstrated a positive association with free testosterone, total testosterone, free androgen index, waist circumference (WC), LH levels, insulin levels, Homeostasis Model Assessment index(HOMA-IR), rIMT and a negative correlation with sex hormone binding globulin in group1 and group2. mFG scores demonstrated a positive association with free testosterone (r = 0.33, p = 0.029) in group3, but no association was found between mFG and WC, HOMA-IR in group3. Our findings indicate that clinical androgen excess may be associated with cardiovascular disease in patients with PCOS.

  9. Polycystic ovary syndrome, adipose tissue and metabolic syndrome.

    Science.gov (United States)

    Delitala, Alessandro P; Capobianco, Giampiero; Delitala, Giuseppe; Cherchi, Pier Luigi; Dessole, Salvatore

    2017-09-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD). A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulin resistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included. PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle. The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

  10. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

    Science.gov (United States)

    Metzler, Veronika M; de Brot, Simone; Robinson, Robert S; Jeyapalan, Jennie N; Rakha, Emad; Walton, Thomas; Gardner, David S; Lund, Emma F; Whitchurch, Jonathan; Haigh, Daisy; Lochray, Jack M; Robinson, Brian D; Allegrucci, Cinzia; Fray, Rupert G; Persson, Jenny L; Ødum, Niels; Miftakhova, Regina R; Rizvanov, Albert A; Hughes, Ieuan A; Tadokoro-Cuccaro, Rieko; Heery, David M; Rutland, Catrin S; Mongan, Nigel P

    2017-08-01

    The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Androgens and Hypertension in Men and Women: a Unifying View.

    Science.gov (United States)

    Moretti, Costanzo; Lanzolla, Giulia; Moretti, Marta; Gnessi, Lucio; Carmina, Enrico

    2017-05-01

    This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality. Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be

  12. [The impact of the androgen receptor splice variant AR-V7 on the prognosis and treatment of advanced prostate cancer].

    Science.gov (United States)

    Thelen, P; Taubert, H; Duensing, S; Kristiansen, G; Merseburger, A S; Cronauer, M V

    2018-01-25

    A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer. This review critically outlines recent advances in AR-V7 diagnostics and presents an overview of current AR-V7 targeted therapies. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Impact of androgen and dietary advanced glycation end products on female rat liver.

    Science.gov (United States)

    Palioura, Eleni; Palimeri, Sotiria; Piperi, Christina; Sakellariou, Stratigoula; Kandaraki, Eleni; Sergentanis, Theodoros; Levidou, Georgia; Agrogiannis, George; Papalois, Apostolos; Korkolopoulou, Penelope; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

    2015-01-01

    Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (x03B3;GT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (pandrogenized animals (p=0.0002). Androgenization per se constitutes an aggravating factor as demonstrated by the elevated x03B3;GT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007). The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions. © 2015 The Author(s) Published by S. Karger AG, Basel.

  14. Selective androgen receptor modulators: in pursuit of tissue-selective androgens.

    Science.gov (United States)

    Omwancha, Josephat; Brown, Terry R

    2006-10-01

    The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

  15. Immunoexpression of androgen receptors and aromatase in testes of patient with Klinefelter's syndrome.

    Directory of Open Access Journals (Sweden)

    Stanisław Fracki

    2005-02-01

    Full Text Available Klinefelter's syndrome (47, XXY is the most common chromosome aneuploidy in men and is usually characterized by underdeveloped testes and sterility. The aim of the present study was to detect cellular distribution of androgen receptors (AR and aromatase in testes of patient with KS. The tissue sections were processed for morphological and immunohistochemical staining. Additionally, levels of FSH, LH, PRL, estradiol, and testosterone were measured in the plasma. Morphological analysis revealed a complete absence of spermatogenesis. No germ cells were present in seminiferous tubules. In some tubules, nests of apparently degenerating Sertoli cells were found. In the interstitium, Leydig cell hyperplasia was observed. Using immunohistochemistry, nuclear AR staining was detected in Sertoli cells and peritubular cells, whereas in Leydig cells the staining was exclusively cytoplasmic. The immunostaining of aromatase was detected in the cytoplasm of Sertoli cells and Leydig cells. Increased levels of gonadotropins and decreased level of testosterone concomitantly with the cytoplasmic localization of AR in Leydig cells might contribute to the impaired testicular function in patient with KS.

  16. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development

    DEFF Research Database (Denmark)

    Metzler, Veronika M.; de Brot, Simone; Robinson, Robert S.

    2017-01-01

    molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further...... supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis...... are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse...

  17. Impact of Androgen and Dietary Advanced Glycation End Products on Female Rat Liver

    Directory of Open Access Journals (Sweden)

    Eleni Palioura

    2015-09-01

    Full Text Available Background/Aims: Advanced glycation end products (AGEs have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS. The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model. Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30 and adult rats (Group B, n=20 that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30. All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months. Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (γGT (p≤0.0002 and indices of AGE immunostaining in liver tissue (pper se constitutes an aggravating factor as demonstrated by the elevated γGT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002 and by the elevated AST and alanine aminotransferase (ALT levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002 followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007. Conclusion: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.

  18. The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maryam Ghotbaddini

    2015-07-01

    Full Text Available The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR. TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models.

  19. A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene

    DEFF Research Database (Denmark)

    Ottesen, A M; Garn, I D; Aksglaede, L

    2007-01-01

    Due to the high prevalence and variable phenotype of patients with Klinefelter syndrome, there is a need for a robust and rapid screening method allowing early diagnosis. Here, we report on the development and detailed clinical validation of a quantitative real-time PCR (qPCR)-based method...... of the copy number assessment of the androgen receptor (AR) gene, located to Xq11.2-q12. We analysed samples from 50 individuals, including a healthy male and female controls and patients with Klinefelter syndrome (47,XXY; 48,XXXY) (n = 28), mosaicisms (46,XX/47,XXY/48XXYY; 45,X/46,XY) (n = 3), other sex......-gene expression. The XIST-expression based assay was correct in only 29/36 samples (81%). Our findings demonstrated that the AR-qPCR technique is a simple and reliable screening method for diagnosis of patients with Klinefelter syndrome or other chromosomal disorders involving an aberrant number of X-chromosomes....

  20. Implications of the 2014 Androgen Excess and Polycystic Ovary Syndrome Society guidelines on polycystic ovarian morphology for polycystic ovary syndrome diagnosis.

    Science.gov (United States)

    Christ, J P; Gunning, M N; Fauser, B C J M

    2017-10-01

    The Androgen Excess and Polycystic Ovary Syndrome Society (AEPCOS) has recommended an updated threshold for polycystic ovarian morphology (PCOM) of 25 follicles or more, 10 ml or more of ovarian volume, or both. We describe the effect of these guidelines on reproductive and metabolic characteristics in 404 women. These women were separated into four groups: group A: hyperandrogenism and oligo-amenorrhoea (n = 157); group B: hyperandrogenism or oligo-amenorrhoea and PCOM meeting AEPCOS 2014 criteria (n = 125); group C: hyperandrogenism or oligo-amenorrhoea and PCOM meeting Rotterdam 2003 but not AEPCOS 2014 criteria (n = 72); and group D: non-PCOS not meeting either criteria (n = 50). Groups B, C and D did not differ across any metabolic markers. The AEPCOS 2014 guidelines may have limited utility in distinguishing metabolic risk factors and result in the exclusion of a large group of oligo-anovulatory women. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  1. Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome.

    Science.gov (United States)

    Luque-Ramírez, Manuel; Mendieta-Azcona, Covadonga; Alvarez-Blasco, Francisco; Escobar-Morreale, Héctor F

    2007-12-01

    We evaluated carotid intima-media thickness (CIMT) as an early marker of atherosclerosis, as well as its main determinants among androgen excess, obesity and insulin resistance, in patients with polycystic ovary syndrome (PCOS). We selected 40 PCOS patients and 20 non-hyperandrogenic women who were similar in terms of age and grade of obesity. Complete clinical, metabolic and hormonal profiles and left common CIMT measurements were obtained. Patients with PCOS presented with increased mean CIMT values when compared with controls (F = 8.575; P = 0.005), and this was independent of obesity. Five PCOS patients but no controls had increased CIMT values. CIMT correlated directly with serum total and free testosterone, androstenedione and dehydroepiandrosterone-sulfate levels and mean 24-h heart rate (HR), and inversely with the insulin sensitivity index (ISI), but no correlation was observed with the body mass index (BMI). Multiple stepwise linear regression models showed that in PCOS patients, the main determinants of CIMT were serum total testosterone or androstenedione concentrations, with no influence of ISI or the mean 24-h HR. Compared with control women, PCOS patients present with an increased CIMT, independent of obesity and related directly to androgen excess; this suggests that hyperandrogenism is associated with atherosclerosis and cardiovascular risk in these women.

  2. Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome.

    Science.gov (United States)

    Dogan, Bercem Aycicek; Arduc, Ayse; Tuna, Mazhar Muslum; Karakılıc, Ersen; Dagdelen, Iffet; Tutuncu, Yasemin; Berker, Dilek; Guler, Serdar

    2014-10-01

    Mean platelet volume (MPV) is generally accepted as a new marker of cardiovascular disease risk in several studies. This study aimed to determine the association of MPV with androgen hormones and insulin resistance (IR) in nonobese patients with polycystic ovary syndrome (PCOS). A total of 136 patients with newly diagnosed reproductive-age PCOS (regarding the criteria of new PCOS phenotypes, based on the Rotterdam criteria) who were nonobese with the mean age of 25 years (25.39 ± 5.51) and mean body mass index (BMI) of 21 kg/m(2) (22.07 ± 2.13) were included. In addition, 59 healthy subjects with mean age of 26 years (22.07 ± 2.13) and mean BMI of 22 kg/m(2) (21.52 ± 3.84) were recruited as control. Total blood count (including MPV), total testosterone, free testosterone, dehydroepiandrosterone-sulfate (DHEAS), and androstenedione levels were recorded. IR was calculated from blood chemistry measurements of fasting insulin and glucose according to updated homeostasis model assessment. No differences were observed in mean MPV values between patients and control group (9.02 fL (8.5-10.1) and 8.9 fL (7.7-9.1), respectively; P = 0.777). MPV values were similar among nonobese patients with and without IR and control subjects (P > 0.05). We detected significantly lower values of MPV in patients with hyperandrogenemia in comparison to patients with normal androgen levels (8.7 and 9.5 fL, P = 0.012). There was a negative correlation between total testosterone, DHEAS, and MPV (P = 0.016, r = -0.229; and P = 0.006, r = -0.261, respectively). Multiple logistic regression analyses confirmed the independence of these associations. Our study revealed that nonobese women with and without PCOS have similar MPV values. While IR does not have any effect on MPV, elevated androgen levels are associated with a low MPV in nonobese patients with PCOS.

  3. Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis

    Directory of Open Access Journals (Sweden)

    L. M. Pérez-López

    2015-01-01

    Full Text Available Introduction. Congenital insensitivity to pain and anhidrosis (CIPA or hereditary sensory and autonomic neuropathy type IV is an extremely rare syndrome. Three clinical findings define the syndrome: insensitivity to pain, impossibility to sweat, and mental retardation. This pathology is caused by a genetic mutation in the NTRK1 gene, which encodes a tyrosine receptor (TrkA for nerve growth factor (NGF. Methods. The consultation of a child female in our center with CIPA and a tibia fracture in pseudoarthrosis encouraged us to carefully review literature and examine the therapeutic possibilities. A thorough review of literature published in Pubmed was done about CIPA and other connected medical issues mentioned in the paper. Conclusions. The therapeutic approach of CIPA remains unclear. The preventive approach remains the only possible treatment of CIPA. We propose two new important concepts in the therapeutic approach for these patients: (1 early surgical treatment for long bone fractures to prevent pseudoarthrosis and to allow early weight bearing, decreasing the risk of further osteopenia, and (2 bisphosphonates to avoid the progression of osteopenia and to reduce the number of consecutive fractures.

  4. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS-like phenotypes in prenatally androgenized rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Ning Xu

    Full Text Available The pathogenesis of polycystic ovary syndrome (PCOS is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD, testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05. Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  5. Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Lin Hui-Ping

    2011-08-01

    Full Text Available Abstract Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients. Cell culture and xenograft studies using androgen receptor (AR-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

  6. Laron syndrome (primary growth hormone insensitivity): a unique model to explore the effect of insulin-like growth factor 1 deficiency on human hair.

    Science.gov (United States)

    Lurie, R; Ben-Amitai, D; Laron, Z

    2004-01-01

    Classical Laron syndrome is a recessive disease of primary insulin-like growth factor 1 (IGF-1) deficiency and primary growth hormone insensitivity. Affected children have, among other defects, sparse hair growth and frontal recessions. The hair is thin and easy to pluck. Young adults have various degrees of alopecia, more pronounced in males. The aim of the present study was to investigate the effect of primary IGF-1 deficiency on hair structure. The study sample included 11 patients with Laron syndrome--5 children (2 untreated) and 6 adults (5 untreated). Hairs were examined by light and electron microscopy. The most significant structured defect, pili torti et canaliculi, was found in 2 young, untreated patients. Grooving, tapered hair and trichorrhexis nodosa were found in the remainder. IGF-1-treated patients had either none or significantly fewer pathological changes compared to the untreated patients. This is the first documentation of the role of primary IGF-1 deficiency on hair structure in human beings. Copyright 2004 S. Karger AG, Basel

  7. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database.

    Science.gov (United States)

    Kumarendran, Balachandran; O'Reilly, Michael W; Manolopoulos, Konstantinos N; Toulis, Konstantinos A; Gokhale, Krishna M; Sitch, Alice J; Wijeyaratne, Chandrika N; Coomarasamy, Arri; Arlt, Wiebke; Nirantharakumar, Krishnarajah

    2018-03-01

    Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86-2.66, p 3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16-4.53, p = 0.017 for 3-3.49 nmol/L and HR = 2.40, 95% CI 1.24-4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

  8. Polycystic ovarian syndrome management options.

    Science.gov (United States)

    Bates, G Wright; Propst, Anthony M

    2012-12-01

    Polycystic ovarian syndrome (PCOS) is a disorder of androgen excess and ovarian dysfunction. Hirsutism and elevated free testosterone levels are the most consistent signs of the androgen excess. Irregular, infrequent, or absent menses and infertility are symptoms of ovulatory dysfunction. Obesity is also a feature of this syndrome and contributes to associated metabolic abnormalities. Lifestyle modification should be the first treatment and is effective in reducing the signs and symptoms. The ovulatory infertility associated with PCOS can be overcome in most cases with oral (clomiphene citrate or letrozole) or injectable (gonadotropins) agents. Surgical intervention is reserved for cases resistant to medical management. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Distribution of steroidogenic enzymes involved in androgen synthesis in polycystic ovaries: an immunohistochemical study

    NARCIS (Netherlands)

    Kaaijk, E. M.; Sasano, H.; Suzuki, T.; Beek, J. F.; van der Veen, F.

    2000-01-01

    To find an explanation for the possible working mechanism of laparoscopic ovarian electrocautery for the treatment of anovulation in polycystic ovarian syndrome (PCOS), we evaluated the distribution of steroidogenic enzymes involved in the synthesis of ovarian androgens in surgical pathology

  10. CLINICAL AND HORMONAL MILIEU OF 9 PATIENTS WITH PRIMARY GROWTH HORMONE INSENSITIVITY SYNDROME AND THEIR RESPONSE TO IGF-I GENERATION TEST

    Directory of Open Access Journals (Sweden)

    M. Razzaghy-Azar

    2006-05-01

    Full Text Available Primary growth hormone insensitivity syndrome (GHIS is a rare entity which can be due to defects in growth hormone (GH receptor that is called type 1 Laron syndrome (T1LS or post receptor defects (type 2 Laron syndrome . The aim of study was determining the clinical and hormonal milieu of the patients with primary GHIS and their response to IGF-I (insulin like growth factor-I generation test (IGT. GH, IGF-I, IGF-II, IGF binding protein 1 and 3 (BP-1 and BP-3, GH binding protein (GHBP and anti-GH antibody were detected by ELISA and RIA methods. IGF-I and BP-3 were measured before and after IGT. Nine patients (8 males, 1 female (mean age ± SD, 6.4 ± 5 years with severe short stature and high GH level were studied. Height SDS was - 8.5 ± 2.6. In 7 patients GHBP was zero, IGF-I and BP-3 were low and did not increase after IGT, so they had T1LS. Two brothers did not show the hormonal milieu of GH receptor defect, and were called non Laron syndrome (NLS. Birth weight in patients with T1LS and NLS was 3.65 ± 0.2 Kg and 1.65 ± 0.2 Kg, respectively (P = 0.001. All of the patients had typical clinical feature of GH-deficiency, but nasal bridge depression and microphallus were not seen in NLS. GH treatment of NLS, normalized their growth velocity, but without catch up growth. In conclusion IGT can differentiate Laron syndrome from other types of short stature. GH and IGF-I of fetus have no role in intrauterine growth.

  11. Do the interactions between glucocorticoids and sex hormones regulate the development of the Metabolic Syndrome?

    Directory of Open Access Journals (Sweden)

    Marià eAlemany

    2012-02-01

    Full Text Available The metabolic syndrome is basically a maturity-onset disease. Typically, its manifestations begin to flourish years after the initial dietary or environmental aggression began. Since most hormonal, metabolic or defense responses are practically immediate, the procrastinated response don't seem justified. Only in childhood, the damages of the metabolic syndrome appear with minimal delay. Sex affects the incidence of the metabolic syndrome, but this is more an effect of timing than absolute gender differences, females holding better than males up to menopause, when the differences between sexes tend to disappear. The metabolic syndrome is related to an immune response, countered by a permanent increase in glucocorticoids, which keep the immune system at bay but also induce insulin resistance, alter the lipid metabolism, favor fat deposition, mobilize protein and decrease androgen synthesis. Androgens limit the operation of glucocorticoids, which is also partly blocked by estrogens, since they decrease inflammation (which enhances glucocorticoid release. These facts suggest that the appearance of the metabolic syndrome symptoms depends on the strength (i.e. levels of androgens and estrogens. The predominance of glucocorticoids and the full manifestation of the syndrome in men are favored by decreased androgen activity. Low androgens can be found in infancy, maturity, advanced age, or because of their inhibition by glucocorticoids (inflammation, stress, medical treatment. Estrogens decrease inflammation and reduce the glucocorticoid response. Low estrogen (infancy, menopause again allow the predominance of glucocorticoids and the manifestation of the metabolic syndrome. It is postulated that the equilibrium between sex hormones and glucocorticoids may be a critical element in the timing of the manifestation of metabolic syndrome-related pathologies.

  12. Resistance to docetaxel in prostate cancer is associated with androgen receptor activation and loss of KDM5D expression

    Science.gov (United States)

    Komura, Kazumasa; Jeong, Seong Ho; Hinohara, Kunihiko; Qu, Fangfang; Wang, Xiaodong; Hiraki, Masayuki; Azuma, Haruhito; Lee, Gwo-Shu Mary; Kantoff, Philip W.; Sweeney, Christopher J.

    2016-01-01

    The androgen receptor (AR) plays an essential role in prostate cancer, and suppression of its signaling with androgen deprivation therapy (ADT) has been the mainstay of treatment for metastatic hormone-sensitive prostate cancer for more than 70 y. Chemotherapy has been reserved for metastatic castration-resistant prostate cancer (mCRPC). The Eastern Cooperative Oncology Group-led trial E3805: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) showed that the addition of docetaxel to ADT prolonged overall survival compared with ADT alone in patients with metastatic hormone-sensitive prostate cancer. This finding suggests that there is an interaction between AR signaling activity and docetaxel sensitivity. Here we demonstrate that the prostate cancer cell lines LNCaP and LAPC4 display markedly different sensitivity to docetaxel with AR activation, and RNA-seq analysis of these cell lines identified KDM5D (lysine-specific demethylase 5D) encoded on the Y chromosome as a potential mediator of this sensitivity. Knocking down KDM5D expression in LNCaP leads to docetaxel resistance in the presence of dihydrotestosterone. KDM5D physically interacts with AR in the nucleus, and regulates its transcriptional activity by demethylating H3K4me3 active transcriptional marks. Attenuating KDM5D expression dysregulates AR signaling, resulting in docetaxel insensitivity. KDM5D deletion was also observed in the LNCaP-derived CRPC cell line 104R2, which displayed docetaxel insensitivity with AR activation, unlike parental LNCaP. Dataset analysis from the Oncomine database revealed significantly decreased KDM5D expression in CRPC and poorer prognosis with low KDM5D expression. Taking these data together, this work indicates that KDM5D modulates the AR axis and that this is associated with altered docetaxel sensitivity. PMID:27185910

  13. Is acne a sign of androgen excess disorder or not?

    Science.gov (United States)

    Uysal, Gulsum; Sahin, Yılmaz; Unluhizarci, Kursad; Ferahbas, Ayten; Uludag, Semih Zeki; Aygen, Ercan; Kelestimur, Fahrettin

    2017-04-01

    Acne is not solely a cosmetic problem. The clinical importance of acne in the estimation of androgen excess disorders is controversial. Recently, the Amsterdam ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group suggested that acne is not commonly associated with hyperandrogenemia and therefore should not be regarded as evidence of hyperandrogenemia. Our aim was to investigate whether acne is a sign of androgen excess disorder or not. This is a cross sectional study that was performed in a university hospital involving 207 women, aged between 18 and 45 years, suffering mainly from acne. The women were assigned as polycystic ovary syndrome (PCOS), idiopathic hirsutism (IH), idiopathic hyperandrogenemia (IHA). Women with acne associated with any of the androgen excess disorders mentioned above were named as hyperandrogenemia associated acne (HAA). Women with acne but without hirsutism and hyperandrogenemia and having ovulatory cycles were named as "isolated acne". Serum luteinizing hormone, follicle stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone-sulfate (DHEAS), androstenedione, total testosterone and lipid levels were measured. Acne score was similar between the women with isolated acne and HAA. The most common cause for acne was PCOS and only 28% of the women had isolated acne. 114 (55%) women had at least one raised serum androgen level. In this study, 72% of acneic women had clinical and/or biochemical hyperandrogenemia. In contrast to the suggestion of ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group, our data indicate that the presence of androgen excess disorders should be evaluated in women presenting with acne. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome

    OpenAIRE

    Erol, Nurdan; Karaagac, Aysu Turkmen; Kounis, Nicholas G

    2014-01-01

    Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female wi...

  15. The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    International Nuclear Information System (INIS)

    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V.

    2010-01-01

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  16. Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Singh Rajender

    Full Text Available OBJECTIVE: Polycystic ovarian syndrome (PCOS refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. METHODS: CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003 inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. RESULTS: CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43 repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29 repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2 = 4.41; P = 0.036, which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CONCLUSION: CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short

  17. Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS).

    Science.gov (United States)

    Rajender, Singh; Carlus, Silas Justin; Bansal, Sandeep Kumar; Negi, Mahendra Pal Singh; Negi, Mahendra Pratap Singh; Sadasivam, Nirmala; Sadasivam, Muthusamy Narayanan; Thangaraj, Kumarasamy

    2013-01-01

    Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk. CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls. CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, χ(2) = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding

  18. Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited Women.

    Science.gov (United States)

    Elhassan, Yasir S; Idkowiak, Jan; Smith, Karen; Asia, Miriam; Gleeson, Helena; Webster, Rachel; Arlt, Wiebke; O'Reilly, Michael W

    2018-03-01

    Androgen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and severity of androgen excess that should be considered predictive of non-PCOS pathology. We examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess. Retrospective review of all women undergoing serum androgen measurement at a large tertiary referral center between 2012 and 2016. Serum A4 and T were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased serum androgen underwent phenotyping by clinical notes review. In 1205 women, DHEAS, A4, and T were measured simultaneously. PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n = 15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4 (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were caused by ACC and severe T excess equally by ACC and OHT. Pattern and severity of androgen excess are important predictors of non-PCOS pathology and may be used to guide further investigations as appropriate.

  19. The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS.

    Science.gov (United States)

    Baculescu, N

    2013-03-15

    Polycystic ovary syndrome (PCOS), one of the most common and complex endocrine disorders affecting up to 15 % of reproductive age women, is considered a predominantly hyperandrogenic syndrome according to the Androgen Excess Society. It is generally accepted that androgens determine the characteristic features of PCOS; in this context, a hyperactive androgen receptor (AR) at the levels of the GnRH pulse generator in the hypothalamus and at the granulosa cells in the ovary, skeletal muscle or adipocytes senses initially normal testosterone and dihydrotestosterone as biochemical hyperandrogenism and might be a crucial connection between the vicious circles of the PCOS pathogenesis. Polymorphism of the AR gene has been associated with different androgen pattern diseases. Several studies have demonstrated an association between AR with increased activity encoded by shorter CAG repeat polymorphism in the exon 1 of the AR gene and PCOS, although there are conflicting results in this field. The phenomenon is more complex because the AR activity is determined by the epigenetic effect of X chromosome inactivation (XCI). Moreover, we must evaluate the AR as a dynamic heterocomplex, with a large number of coactivators and corepressors that are essential to its function, thus mediating tissue-specific effects. In theory, any of these factors could modify the activity of AR, which likely explains the inconsistent results obtained when this activity was quantified by only the CAG polymorphism in PCOS.

  20. Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis.

    Science.gov (United States)

    Sherman, Shermel; Sarsour, Nadeen; Salehi, Marziyeh; Schroering, Allen; Mell, Blair; Joe, Bina; Hill, Jennifer W

    2018-02-22

    Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in

  1. Cardiovascular risk factors and events in women with androgen excess.

    Science.gov (United States)

    Macut, D; Antić, I B; Bjekić-Macut, J

    2015-03-01

    Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

  2. Androgen Bioassay for the Detection of Nonlabeled Androgenic Compounds in Nutritional Supplements.

    Science.gov (United States)

    Cooper, Elliot R; McGrath, Kristine C Y; Li, XiaoHong; Heather, Alison K

    2018-01-01

    Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.

  3. In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis

    Science.gov (United States)

    Connolly, Fiona; Rae, Michael T.; Späth, Katharina; Boswell, Lyndsey; McNeilly, Alan S.; Duncan, W. Colin

    2015-01-01

    Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. PMID:26148093

  4. Dissecting phenotypic variation among AIS patients

    International Nuclear Information System (INIS)

    Wang Minghua; Wang Jiucun; Zhang Zhen; Zhao Zhimin; Zhang Rongmei; Hu Xiaohua; Tan Tao; Luo Shijing; Luo Zewei

    2005-01-01

    We have created genital skin fibroblast cell lines directly from three patients in a Chinese family affected by androgen insensitivity syndrome (AIS). All patients in the family share an identical AR Arg 840 Cys mutant but show different disease phenotypes. By using the cell lines, we find that the mutation has not influenced a normal androgen-binding capacity at 37 deg C but has reduced the affinity for androgens and may cause thermolability of the androgen-receptor complex. The impaired nuclear trafficking of the androgen receptor in the cell lines is highly correlated with the severity of donors' disease phenotype. The transactivity of the mutant is substantially weakened and the extent of the reduced transactivity reflects severity of the donors' disease symptom. Our data reveal that although etiology of AIS is monogenic and the mutant may alter the major biological functions of its wild allele, the function of the mutant AR can also be influenced by the different genetic backgrounds and thus explains the divergent disease phenotypes

  5. Effects of male sex hormones on gender identity, sexual behavior, and cognitive function.

    Science.gov (United States)

    Zhu, Yuan-shan; Cai, Li-qun

    2006-04-01

    Androgens, the male sex hormones, play an essential role in male sexual differentiation and development. However, the influence of these sex hormones extends beyond their roles in sexual differentiation and development. In many animal species, sex hormones have been shown to be essential for sexual differentiation of the brain during development and for maintaining sexually dimorphic behavior throughout life. The principals of sex determination in humans have been demonstrated to be similar to other mammals. However, the hormonal influence on sexual dimorphic differences in the nervous system in humans, sex differences in behaviors, and its correlations with those of other mammals is still an emerging field. In this review, the roles of androgens in gender and cognitive function are discussed with the emphasis on subjects with androgen action defects including complete androgen insensitivity due to androgen receptor mutations and 5alpha-reductase-2 deficiency syndromes due to 5alpha-reductase-2 gene mutations. The issue of the complex interaction of nature versus nurture is addressed.

  6. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report.

    Science.gov (United States)

    Azziz, Ricardo; Carmina, Enrico; Dewailly, Didier; Diamanti-Kandarakis, Evanthia; Escobar-Morreale, Héctor F; Futterweit, Walter; Janssen, Onno E; Legro, Richard S; Norman, Robert J; Taylor, Ann E; Witchel, Selma F

    2009-02-01

    To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research. Literature review and expert consensus. Professional society. None. None. A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence. Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.

  7. Severe obstructive sleep apnoea syndrome in an adult patient with Laron syndrome.

    Science.gov (United States)

    Dagan, Y; Abadi, J; Lifschitz, A; Laron, Z

    2001-08-01

    A 68 year old patient with Laron syndrome (primary growth hormone (GH) resistance-insensitivity due to a molecular defect of the GH receptor) and severe obstructive sleep apnoea syndrome is described. Treatment with continuous positive air pressure therapy resulted in improved nocturnal sleep, daytime alertness and cognitive functions. Copyright 2001 Harcourt Publishers Ltd.

  8. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  9. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells.

  10. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    Science.gov (United States)

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  11. The PPAR{gamma} ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V., E-mail: lstewart@mmc.edu

    2010-12-10

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPAR{gamma} ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPAR{gamma} ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPAR{gamma} ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPAR{gamma}. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPAR{gamma} and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  12. Gender identity and gender role orientation in female assigned patients with disorders of sex development.

    Science.gov (United States)

    Mattila, Aino K; Fagerholm, Riitta; Santtila, Pekka; Miettinen, Päivi J; Taskinen, Seppo

    2012-11-01

    Gender identity and gender role orientation were assessed in 24 female assigned patients with disorders of sex development. A total of 16 patients were prenatally exposed to androgens, of whom 15 had congenital adrenal hyperplasia and 1 was virilized due to maternal tumor. Eight patients had 46,XY karyotype, of whom 5 had partial and 3 had complete androgen insensitivity syndrome. Gender identity was measured by the 27-item Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults with 167 female medical students as controls, and gender role was assessed by the femininity and masculinity subscales of the 30-item Bem Sex Role Inventory with 104 female and 64 male medical students as controls. No patient reached the cutoff for gender identity disorder on the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. However, patients with 46,XY karyotype demonstrated a somewhat more conflicted gender identity, although the overall differences were relatively small. As to gender role orientation, patients with complete androgen insensitivity syndrome had high scores on the femininity and masculinity scales of the Bem Sex Role Inventory, which made them the most androgynous group. Our findings, although clinically not clear cut, suggest that patients with disorders of sex development are a heterogeneous group regarding gender identity and gender role outcomes, and that this issue should be discussed with the family when treatment plans are made. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  13. Changes of pituitary gland volume in Kennedy disease.

    Science.gov (United States)

    Pieper, C C; Teismann, I K; Konrad, C; Heindel, W L; Schiffbauer, H

    2013-12-01

    Kennedy disease is a rare X-linked neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the androgen-receptor gene. Apart from neurologic signs, this mutation can cause a partial androgen insensitivity syndrome with typical alterations of gonadotropic hormones produced by the pituitary gland. The aim of the present study was therefore to evaluate the impact of Kennedy disease on pituitary gland volume under the hypothesis that endocrinologic changes caused by partial androgen insensitivity may lead to morphologic changes (ie, hypertrophy) of the pituitary gland. Pituitary gland volume was measured in sagittal sections of 3D T1-weighted 3T-MR imaging data of 8 patients with genetically proven Kennedy disease and compared with 16 healthy age-matched control subjects by use of Multitracer by a blinded, experienced radiologist. The results were analyzed by a univariant ANOVA with total brain volume as a covariant. Furthermore, correlation and linear regression analyses were performed for pituitary volume, patient age, disease duration, and CAG repeat expansion length. Intraobserver reliability was evaluated by means of the Pearson correlation coefficient. Pituitary volume was significantly larger in patients with Kennedy disease (636 [±90] mm(3)) than in healthy control subjects (534 [±91] mm(3)) (P = .041). There was no significant difference in total brain volume (P = .379). Control subjects showed a significant decrease in volume with age (r = -0.712, P = .002), whereas there was a trend to increasing gland volume in patients with Kennedy disease (r = 0.443, P = .272). Gland volume correlated with CAG repeat expansion length in patients (r = 0.630, P = .047). The correlation coefficient for intraobserver reliability was 0.94 (P pituitary volume that correlated with the CAG repeat expansion length. This could reflect hypertrophy as the result of elevated gonadotropic hormone secretion caused by the androgen receptor mutation with partial

  14. Controversies of Sex Re-assignment in Genetic Males with Congenital Inadequacy of the Penis.

    Science.gov (United States)

    Raveenthiran, Venkatachalam

    2017-09-01

    Sex assignment in 46XY genetic male children with congenital inadequacy of the penis (CIP) is controversial. Traditionally, children with penile length less than 2 cm at birth are considered unsuitable to be raised as males. They are typically re-assigned to female-sex and feminizing genitoplasty is usually done in infancy. However, the concept of cerebral androgen imprinting has caused paradigm shift in the philosophy of sex re-assignment. Masculinization of the brain, rather than length of the penis, is the modern criterion of sex re-assignment in CIP. This review summarizes the current understanding of the complex issue. In 46XY children with CIP, male-sex assignment appears appropriate in non-hormonal conditions such as idiopathic micropenis, aphallia and exstrophy. Female-sex re-assignment appears acceptable in complete androgen insensitivity (CAIS), while partial androgen insensitivity syndrome (PAIS) patients are highly dissatisfied with the assignment of either sex. Children with 5-alpha reductase deficiency are likely to have spontaneous penile lengthening at puberty. Hence, they are better raised as males. Although female assignment is common in pure gonadal dysgenesis, long-term results are not known to justify the decision.

  15. A rare case of congenital insensitivity to pain with anhydrosiss

    Directory of Open Access Journals (Sweden)

    Govardhani Yanamadala

    2015-01-01

    Full Text Available Congenital insensitivity to pain syndrome with anhydrosis (CIPA is a rare inherited disorder. It is characterized by loss of pain and temperature sensation, lack of sweating and mild mental retardation. This disorder belongs to hereditary sensory and autonomic neuropathy family (type IV. Because of these abnormalities, patients require special anesthetic care. They include titration of intraoperative opioids, an anesthetic to ensure co-operation and immobility and intra-operative temperature monitoring. Here we report a 7-year-old female child with CIPA posted for restoration and cementation for dental caries along with sural nerve and skin biopsy.

  16. Androgens and alopecia.

    Science.gov (United States)

    Kaufman, Keith D

    2002-12-30

    Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences. Copyright 2002 Elsevier Science Ireland Ltd.

  17. PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion

    International Nuclear Information System (INIS)

    Zhang, Zheng; Jin, Bo; Jin, Yaqiong; Huang, Shengquan; Niu, Xiaohua; Mao, Zebin; Xin, Dianqi

    2017-01-01

    Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that the PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the −851 to −836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis. - Highlights: • Androgen treatment of LNCaP cells induced PTTG1 expression. • Knockdown of PTTG1 expression significantly reduced androgen-induced LNCaP cell growth and invasion. • PTTG1 is highly expressed in metastasis prostate cancer tissue. • PTTG1 is a novel downstream target gene of androgen receptor.

  18. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  19. Testosterone deficiency syndrome: cellular and molecular mechanism of action.

    Science.gov (United States)

    Carruthers, Malcolm

    2013-02-01

    There is virtually no correlation between what are generally accepted to be the symptoms of deficient androgen in men and levels of androgens as measured in the laboratory. Now that androgen deficiency is being shown to play a part in conditions as diverse as metabolic syndrome, diabetes, and coronary heart disease, a hypothesis is needed to explain this apparent discrepancy between measured androgen levels and our understanding of the symptoms of androgen deficiency. When the possible mechanisms for androgen actions are considered, one explanation emerges that androgen may act much like insulin in persons with type 2 diabetes mellitus: the degree of androgen resistance may be variable depending on the organs or systems considered. Therefore, the symptoms can result from altered or damaged synthesis of androgen synthesis or regulation, elevated androgen binding, a reduction in tissue response, or decreased as a result of polymorphism and aging. Genomic transcription and translation may also be affected. As with diabetes, in adult male androgen deficiency, it is suggested that the definition of androgen deficiency should be based on individual physiology, with the requirements of the individual at a particular stage of life setting the baseline against which any deficiency of androgens or androgen metabolites, either absolute or relative, is determined. This approach will affect the terminology, etiology, diagnosis, and treatment of androgen deficiency.

  20. Prevalence of Polycystic Ovary Syndrome in Women from Opposite-Sex Twin Pairs

    NARCIS (Netherlands)

    Kuijper, E.A.M.; Vink, J.M.; Lambalk, C.B.; Boomsma, D.I.

    2009-01-01

    Introduction: Intrauterine androgens of a male fetus may influence the female fetus in opposite-sex twin pairs. Because female intrauterine overexposure to androgens could lead to polycystic ovary syndrome (PCOS), the prevalence of PCOS should be higher in women from opposite-sex twin pairs.

  1. Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors.

    Science.gov (United States)

    Sanchón, Raúl; Gambineri, Alessandra; Alpañés, Macarena; Martínez-García, M Ángeles; Pasquali, Renato; Escobar-Morreale, Héctor F

    2012-04-01

    The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism. A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism. Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5-14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7-2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6-7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3-5.4). Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopausal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.

  2. Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

    Science.gov (United States)

    Condorelli, R A; Calogero, A E; Di Mauro, M; Mongioi', L M; Cannarella, R; Rosta, G; La Vignera, S

    2018-04-01

    Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE ® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

  3. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database

    Science.gov (United States)

    Kumarendran, Balachandran; O’Reilly, Michael W.; Manolopoulos, Konstantinos N.; Toulis, Konstantinos A.; Gokhale, Krishna M.; Sitch, Alice J.; Wijeyaratne, Chandrika N.; Coomarasamy, Arri

    2018-01-01

    Background Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. Methods and findings We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p 3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53, p = 0.017 for 3–3.49 nmol/L and HR = 2.40, 95% CI 1.24–4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44–9.25, p < 0.001 for 20–29.99 nmol/L and HR = 4.98, 95% CI 2.45–10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. Conclusions We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered. PMID:29590099

  4. Androgen Receptor Signaling in Bladder Cancer

    Science.gov (United States)

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

  5. Androgen Receptor Signaling in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-02-01

    Full Text Available Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer.

  6. Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer

    NARCIS (Netherlands)

    L.J. Blok (Leen); G.T.G. Chang; M. Steenbeek-Slotboom (M.); W.M. van Weerden (Wytske); H.G. Swarts; J.J.H.H.M. de Pont (J. J H H M); G.J. van Steenbrugge (Gert Jan); A.O. Brinkmann (Albert)

    1999-01-01

    textabstractThe β1-subunit of Na+,K+-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of

  7. The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?

    Directory of Open Access Journals (Sweden)

    Haendler Bernard

    2008-12-01

    Full Text Available Abstract Background Based on the observation of an increased number of paralogous genes in teleost fishes compared with other vertebrates and on the conserved synteny between duplicated copies, it has been shown that a whole genome duplication (WGD occurred during the evolution of Actinopterygian fish. Comparative phylogenetic dating of this duplication event suggests that it occurred early on, specifically in teleosts. It has been proposed that this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish, notably by allowing the sub- or neo-functionalization of many duplicated genes. Results In this paper, we studied in a wide range of Actinopterygians the duplication and fate of the androgen receptor (AR, NR3C4, a nuclear receptor known to play a key role in sex-determination in vertebrates. The pattern of AR gene duplication is consistent with an early WGD event: it has been duplicated into two genes AR-A and AR-B after the split of the Acipenseriformes from the lineage leading to teleost fish but before the divergence of Osteoglossiformes. Genomic and syntenic analyses in addition to lack of PCR amplification show that one of the duplicated copies, AR-B, was lost in several basal Clupeocephala such as Cypriniformes (including the model species zebrafish, Siluriformes, Characiformes and Salmoniformes. Interestingly, we also found that, in basal teleost fish (Osteoglossiformes and Anguilliformes, the two copies remain very similar, whereas, specifically in Percomorphs, one of the copies, AR-B, has accumulated substitutions in both the ligand binding domain (LBD and the DNA binding domain (DBD. Conclusion The comparison of the mutations present in these divergent AR-B with those known in human to be implicated in complete, partial or mild androgen insensitivity syndrome suggests that the existence of two distinct AR duplicates may be correlated to specific functional differences that may be

  8. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    OpenAIRE

    Chadha, D.; Pache, T.D.; Huikeshoven, Frans; Brinkmann, Albert; Kwast, Theo

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycy...

  9. Insensitive Munitions Testing

    Data.gov (United States)

    Federal Laboratory Consortium — Insensitive Munitions Testing at RTC is conducted (IAW MILSTD-2105) at Test Area 4. Our engineers and technicians obtain data for hazards classification and safety...

  10. Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

    Science.gov (United States)

    Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter A; Christman, Gregory M; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Schlaff, William; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

    2017-08-01

    While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

    Science.gov (United States)

    Chan, Angel O K; But, W M; Lee, C Y; Lam, Y Y; Ng, K L; Loung, P Y; Lam, Aimen; Cheng, C W; Shek, C C; Wong, W S; Wong, K F; Wong, M Y; Tse, W Y

    2015-12-01

    Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. Five public hospitals in Hong Kong. Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

  12. Disorders of sex development: a study of 194 cases

    Directory of Open Access Journals (Sweden)

    R Walia

    2018-02-01

    Full Text Available Objective: To study the clinical profile and the management of patients with disorders of sex development (DSD. Design and setting: Retrospective study from a tertiary care hospital of North India. Methods and patients: One hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included. Results: One hundred and two patients (52.5% had 46,XY DSD and seventy-four patients (38.1% had 46,XX DSD. Sex chromosome DSD was identified in seven (3.6% patients. Of 102 patients with 46,XY DSD, 32 (31.4% had androgen insensitivity syndrome and 26 (25.5% had androgen biosynthetic defect. Of the 74 patients with 46,XX DSD, 52 (70.27% had congenital adrenal hyperplasia (CAH and eight (10.8% had ovotesticular DSD. Five patients with sex chromosome DSD had mixed gonadal dysgenesis. Excluding CAH, majority of the patients (90% presented in the post-pubertal period. One-fourth of the patients with simple virilising CAH were reared as males because of strong male gender identity and behaviour and firm insistence by the parents. Corrective surgeries were performed in twenty patients (20% of 46,XY DSD without hormonal evaluation prior to the presentation. Conclusion: Congenital adrenal hyperplasia is the most common DSD in the present series. Most common XY DSD is androgen insensitivity syndrome, while CAH is the most common XX DSD. Delayed diagnosis is a common feature, and corrective surgeries are performed without seeking a definite diagnosis.

  13. Androgen Receptor Signaling in Bladder Cancer

    OpenAIRE

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in u...

  14. Endogenous Androgens and Sex Hormone-Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes.

    Science.gov (United States)

    Fenske, Benjamin; Kische, Hanna; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Keevil, Brian G; Brabant, Georg; Haring, Robin

    2015-12-01

    The association of endogenous androgens and sex hormone-binding globulin (SHBG) with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) mostly 23562 refers to small and selected study samples with immunoassay-based measurements. Thus, we investigated the association of hormone levels with MetS and T2DM in women from a large population-based sample. A total of 2077 women from the Study of Health in Pomerania were assessed at baseline (N = 3160, 1997-2001) and 5-year follow-up (N = 1711, 2002-2006). We investigated associations of total testosterone (T) and androstenedione measured by liquid chromatography-tandem mass spectrometry, SHBG by immunoassay, and free T and free androgen index with MetS and T2DM. Baseline prevalence of MetS and T2DM was 23.1% (N = 365) and 9.5% (N = 196), with an incidence of 17.7 and 7.0 per 1.000 person-years, respectively. Cross-sectional analyses yielded inverse associations of SHBG with MetS (relative risk [RR], 0.67; 95% confidence interval [CI], 0.60-0.74) and T2DM (RR, 0.61; 95% CI, 0.50-0.74) after multivariable adjustment. In longitudinal analyses, only age-adjusted models showed an inverse association of baseline SHBG with incident MetS (RR, 0.61; 95% CI, 0.51-0.73) and T2DM (RR, 0.58; 95% CI, 0.43-0.78). Multivariable-adjusted models stratified by menopausal status revealed an inverse association between SHBG and incident MetS risk in postmenopausal women (RR, 0.65; 95% CI, 0.51-0.81). This longitudinal population-based study revealed independent inverse associations of SHBG with MetS and T2DM, suggesting low SHBG as a potential risk marker for cardiometabolic morbidity, especially among postmenopausal women.

  15. Sarcopenia and androgens: A link between pathology and treatment

    Directory of Open Access Journals (Sweden)

    Carla eBasualto-Alarcón

    2014-12-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle mass and function, is becoming more prevalent as the lifespan continues to increase in most populations. As sarcopenia is highly disabling, being associated with increased risk of dependence, falls, fractures, weakness, disability, and death, development of approaches to its prevention and treatment are required. Androgens are the main physiologic anabolic steroid hormones and normal testosterone levels are necessary for a range of developmental and biological processes, including maintenance of muscle mass. Testosterone concentrations decline as age increase, suggesting that low plasma testosterone levels can cause or accelerate muscle- and age-related diseases, as sarcopenia. Currently, there is increasing interest on the anabolic properties of testosterone for therapeutic use in muscle diseases including sarcopenia. However, the pathophysiological mechanisms underlying this muscle syndrome and its relationship with plasma level of androgens are not completely understood. This review discusses the recent findings regarding sarcopenia, the intrinsic and extrinsic mechanisms involved in the onset and progression of this disease and the treatment approaches that have been developed based on testosterone deficiency and their implications.

  16. Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome.

    Science.gov (United States)

    Duquesnoy, P; Sobrier, M L; Amselem, S; Goossens, M

    1991-01-01

    Mutations in the growth hormone receptor (GHR) gene can cause growth hormone (GH) resistance. Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism. We have previously identified a mutation within the extracellular domain of this receptor, replacing phenylalanine by serine at position 96 of the mature protein, in a patient with Laron syndrome. We have now investigated the effect of this Phe----Ser substitution on hormone binding activity by expressing the total human GHR cDNA and mutant form in eukaryotic cells. The wild-type protein expressed was able to bind GH but no plasma membrane binding was detectable on cells transfected with the mutant cDNA; this was also the case of cells transfected with a Phe96----Ala mutant cDNA, suggesting that the lack of binding activity is not due to a posttranslational modification of serine. Examination of the variant proteins in subcellular fractions revealed the presence of specific GH binding activity in the lysosomal fraction, whereas immunofluorescence studies located mutant proteins in the cytosol. Our findings suggest that these mutant GHRs fail to follow the correct intracellular transport pathway and underline the potential importance of this phenylalanine residue, which is conserved among the GH, prolactin, and erythropoietin receptors that belong to the same cytokine receptor superfamily. Images PMID:1719554

  17. Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep

    OpenAIRE

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

    2015-01-01

    Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insuli...

  18. Androgen regulation of the androgen receptor coregulators

    International Nuclear Information System (INIS)

    Urbanucci, Alfonso; Waltering, Kati K; Suikki, Hanna E; Helenius, Merja A; Visakorpi, Tapio

    2008-01-01

    The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer. The aim of this study was to identify coregulators whose expression is regulated by either the androgens and/or by the expression level of AR. We used empty vector and AR cDNA-transfected LNCaP cells (LNCaP-pcDNA3.1, and LNCaP-ARhi, respectively), and grew them for 4 and 24 hours in the presence of dihydrotestosterone (DHT) at various concentrations. The expression of 25 AR coregulators (SRC1, TIF2, PIAS1, PIASx, ARIP4, BRCA1, β-catenin, AIB3, AIB1, CBP, STAT1, NCoR1, AES, cyclin D1, p300, ARA24, LSD1, BAG1L, gelsolin, prohibitin, JMJD2C, JMJD1A, MAK, PAK6 and MAGE11) was then measured by using real-time quantitative RT-PCR (Q-RT-PCR). Five of the coregulators (AIB1, CBP, MAK, BRCA1 and β-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of β-catenin, cyclinD1 and gelsolin. In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens

  19. Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.

    Science.gov (United States)

    Lewandowski, Krzysztof C; Cajdler-Luba, Agata; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

    2011-01-01

    As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, pPCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

  20. A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective.

    Science.gov (United States)

    Rosenbloom, Arlan L

    2016-06-01

    A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). Rare

  1. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism.

    Science.gov (United States)

    Carmina, E; Rosato, F; Jannì, A; Rizzo, M; Longo, R A

    2006-01-01

    We undertook this study to estimate the prevalence of the various androgen excess disorders using the new criteria suggested for the diagnosis of polycystic ovary syndrome (PCOS). The study was performed at two endocrine departments at the University of Palermo (Palermo, Italy). The records of all patients referred between 1980 and 2004 for evaluation of clinical hyperandrogenism were reevaluated. All past diagnoses were reviewed using the actual diagnostic criteria. To be included in this study, the records of the patients had to present the following available data: clinical evaluation of hyperandrogenism, body weight and height, testosterone (T), free T, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, progesterone, and pelvic sonography. A total of 1226 consecutive patients were seen during the study period, but only the scores of 950 patients satisfied all criteria and were reassessed for the diagnosis. The prevalence of androgen excess disorders was: PCOS, 72.1% (classic anovulatory patients, 56.6%; mild ovulatory patients, 15.5%), idiopathic hyperandrogenism, 15.8%; idiopathic hirsutism, 7.6%; 21-hydroxylase-deficient nonclassic adrenal hyperplasia, 4.3%; and androgen-secreting tumors, 0.2%. Compared with other androgen excess disorders, patients with PCOS had increased body weight whereas nonclassic adrenal hyperplasia patients were younger and more hirsute and had higher serum levels of T, free T, and 17-hydroxyprogesterone. Classic PCOS is the most common androgen excess disorder. However, mild androgen excess disorders (ovulatory PCOS and idiopathic hyperandrogenism) are also common and, in an endocrine setting, include about 30% of patients with clinical hyperandrogenism.

  2. Polycystic Ovary Syndrome - diagnosis and treatment

    OpenAIRE

    Hussain, Amna

    2015-01-01

    Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder, and a major cause of infertility in women. An excessive amount of androgen hormones are produced by polycystic ovaries in PCOS with irregular menstruation and anovulation as result. The most common early symptoms are infertility, hirsutism and acne. Type 2 diabetes mellitus, metabolic syndrome, and possibly cardiovascular disease and endometrial carcinoma are all associated as lifelong implications with t...

  3. Effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome patients.

    Science.gov (United States)

    Karadağ, Cihan; Yoldemir, Tevfik; Yavuz, Dilek Gogas

    2018-02-01

    The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS. © 2017 Japan Society of Obstetrics and Gynecology.

  4. Pituitary size in patients with Laron syndrome (primary GH insensitivity).

    Science.gov (United States)

    Kornreich, Liora; Horev, Gadi; Schwarz, Michael; Karmazyn, Boaz; Laron, Zvi

    2003-03-01

    The purpose of the present study was to investigate whether lifelong secretion of high levels of GH, characteristic of Laron syndrome, leads to an increase in the size of the pituitary gland. Eleven patients (six females, five males) with Laron syndrome underwent magnetic resonance imaging of the pituitary region with a system operating at 0.5 T. There were nine adults aged 36-68 Years and two children, a 4-Year-old boy and a 9-Year-old girl. The latter patient had been treated with IGF-I (150-180 mg/kg per day) since the age of 3 Years; all the other patients were untreated. The height of the adenohypophysis was measured on the sagittal images and compared with reference values for age and sex. The height of the adenohypophysis was within the normal range for age and gender in all patients, except for one male, who had a small gland. No congenital anomalies of the pituitary-hypothalamic region were detected. Despite the lifelong high levels of GH, no pituitary hypertrophy was detected. The anatomy of the pituitary-hypothalamic region in Laron syndrome is normal.

  5. Using the androgen excess-PCOS society criteria to diagnose polycystic ovary syndrome and the risk of metabolic syndrome in adolescents.

    Science.gov (United States)

    Roe, Andrea Hsu; Prochaska, Erica; Smith, Matthew; Sammel, Mary; Dokras, Anuja

    2013-05-01

    To use the Androgen Excess-PCOS Society (AE-PCOS) criteria in adolescents to diagnose polycystic ovary syndrome (PCOS) and identify the prevalence of metabolic risk factors. Retrospective chart review of adolescents (>2 years postmenarche) presenting at a specialty clinic from 2008 through 2010 with complete evaluation for PCOS and metabolic risk were reviewed. Metabolic risk in adolescents with PCOS was compared with those with ≤ 1 AE-PCOS criteria. Of the 205 adolescents evaluated, 66% were found to have PCOS based on the AE-PCOS criteria. The most common presenting symptom was menstrual irregularity, followed by acne, hirsutism, and weight gain. Adolescents with PCOS had a significantly higher prevalence of obesity, hypertension, and low level of high-density lipoprotein cholesterol. Subjects with PCOS had ≥ 1 metabolic risk factor compared with the subjects without PCOS (63.6% vs 33.3%, P = .002). More adolescents with PCOS had ≥ 2 abnormal metabolic risk factors excluding body mass index compared with those without PCOS (P PCOS compared with 1.7% in those without PCOS (P PCOS based on the AE-PCOS criteria are at a significantly increased risk of ≥ 1 metabolic abnormality. Our data underscore the need to accurately diagnose PCOS in the adolescent population instead of delaying the diagnosis to adulthood. Further, using similar criteria for the diagnosis of PCOS in adolescents (>2 years postmenarche) and adults will be more convenient for the clinician. Copyright © 2013 Mosby, Inc. All rights reserved.

  6. Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione.

    Science.gov (United States)

    O'Reilly, Michael W; Taylor, Angela E; Crabtree, Nicola J; Hughes, Beverly A; Capper, Farfia; Crowley, Rachel K; Stewart, Paul M; Tomlinson, Jeremy W; Arlt, Wiebke

    2014-03-01

    Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P androgen excretion than NA/NT (P androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03). Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess.

  7. Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor

    Science.gov (United States)

    Coleman, Daniel J.; Van Hook, Kathryn; King, Carly J.; Schwartzman, Jacob; Lisac, Robert; Urrutia, Joshua; Sehrawat, Archana; Woodward, Josha; Wang, Nicholas J.; Gulati, Roman; Thomas, George V.; Beer, Tomasz M.; Gleave, Martin; Korkola, James E.; Gao, Lina; Heiser, Laura M.; Alumkal, Joshi J.

    2016-01-01

    Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) – the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. PMID:27276681

  8. Riscos cardiovasculares do bloqueio androgênico Riesgos cardiovasculares del bloqueo androgénico Cardiovascular risks of androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Adriano Freitas Ribeiro

    2010-09-01

    Full Text Available O adenocarcinoma de próstata é o câncer mais comum no sexo masculino após o câncer de pele. Entre as várias formas de tratamento do câncer de próstata, a terapia de bloqueio androgênico é uma modalidade consagrada nos pacientes com doença metastática ou localmente avançada, que provavelmente resulta em aumento de sobrevida. No entanto, o bloqueio androgênico é causador de uma série de consequências adversas. Complicações como osteoporose, disfunção sexual, ginecomastia, anemia e alterações na composição corporal são bem conhecidas. Recentemente, uma série de complicações metabólicas foi descrita como aumento da circunferência abdominal, resistência à insulina, hiperglicemia, diabete, dislipidemia e síndrome metabólica com consequente aumento do risco de eventos coronarianos e mortalidade cardiovascular nessa população específica. Este artigo de atualização apresenta uma revisão bibliográfica realizada no MEDLINE de toda literatura publicada em inglês no período de 1966 até junho de 2009, com as seguintes palavras-chave: androgen deprivation therapy, androgen supression therapy, hormone treatment, prostate cancer, metabolic syndrome e cardiovascular disease, no intuito de analisar quais seriam os reais riscos cardiovasculares da terapia de deprivação androgênica, também chamada bloqueio androgênico, nos pacientes com câncer de próstata.El adenocarcinoma de próstata es el cáncer más común en el sexo masculino después del cáncer de piel. Entre las varias formas de tratamiento del cáncer de próstata, la terapia de bloqueo androgénico es una modalidad consagrada en los pacientes con enfermedad metastásica o localmente avanzada, que probablemente resulta en aumento de sobrevida. Mientras tanto, el bloqueo androgénico es causante de una serie de consecuencias adversas. Complicaciones como osteoporosis, disfunción sexual, ginecomastia, anemia y alteraciones en la composición corporal son

  9. Vitamin D is associated with bioavailability of androgens in eumenorrheic women with prior pregnancy loss.

    Science.gov (United States)

    Kuhr, Daniel L; Sjaarda, Lindsey A; Alkhalaf, Zeina; Omosigho, Ukpebo R; Connell, Matthew T; Silver, Robert M; Kim, Keewan; Perkins, Neil J; Holland, Tiffany L; Plowden, Torie C; Schisterman, Enrique F; Mumford, Sunni L

    2018-06-01

    Prior studies have reported mixed results regarding relationships between vitamin D, androgens, and sex hormone-binding globulin in patients with polycystic ovary syndrome. However, less is known regarding these associations in eumenorrheic, premenopausal women. Our objective was to study the relationships between serum vitamin D and androgen biomarkers in eumenorrheic women with a history of pregnancy loss who were attempting pregnancy. This was an analysis of a cohort of 1191 participants from the Effects of Aspirin in Gestation and Reproduction trial (2006-2012). Participants were attempting to conceive, aged 18-40 years, with 1-2 documented prior pregnancy losses and no history of infertility, and recruited from 4 academic medical centers in the United States. Serum vitamin D (25-hydroxyvitamin D) and hormone concentrations were measured at baseline. Vitamin D concentration was negatively associated with free androgen index (percentage change [95% confidence interval, -5% (-8% to -2%)] per 10 ng/mL increase) and positively associated with sex hormone-binding globulin (95% confidence interval, 4% [2-7%]), although not with total testosterone, free testosterone, or dehydroepiandrosterone sulfate after adjusting for age, body mass index, smoking status, race, income, education, physical activity, and season of blood draw. Overall, vitamin D was associated with sex hormone-binding globulin and free androgen index in eumenorrheic women with prior pregnancy loss, suggesting that vitamin D may play a role in the bioavailability of androgens in eumenorrheic women. We are limited in making assessments regarding directionality, given the cross-sectional nature of our study. Copyright © 2018. Published by Elsevier Inc.

  10. Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes

    International Nuclear Information System (INIS)

    Olsen, Jan Roger; Azeem, Waqas; Hellem, Margrete Reime; Marvyin, Kristo; Hua, Yaping; Qu, Yi; Li, Lisha; Lin, Biaoyang; Ke, XI- Song; Øyan, Anne Margrete; Kalland, Karl- Henning

    2016-01-01

    Expression of the androgen receptor (AR) is associated with androgen-dependent proliferation arrest and terminal differentiation of normal prostate epithelial cells. Additionally, activation of the AR is required for survival of benign luminal epithelial cells and primary cancer cells, thus androgen deprivation therapy (ADT) leads to apoptosis in both benign and cancerous tissue. Escape from ADT is known as castration-resistant prostate cancer (CRPC). In the course of CRPC development the AR typically switches from being a cell-intrinsic inhibitor of normal prostate epithelial cell proliferation to becoming an oncogene that is critical for prostate cancer cell proliferation. A clearer understanding of the context dependent activation of the AR and its target genes is therefore desirable. Immortalized human prostate basal epithelial EP156T cells and progeny cells that underwent epithelial to mesenchymal transition (EMT), primary prostate epithelial cells (PrECs) and prostate cancer cell lines LNCaP, VCaP and 22Rv1 were used to examine context dependent restriction and activation of the AR and classical target genes, such as KLK3. Genome-wide gene expression analyses and single cell protein analyses were applied to study the effect of different contexts. A variety of growth conditions were tested and found unable to activate AR expression and transcription of classical androgen-dependent AR target genes, such as KLK3, in prostate epithelial cells with basal cell features or in mesenchymal type prostate cells. The restriction of androgen- and AR-dependent transcription of classical target genes in prostate basal epithelial cells was at the level of AR expression. Exogenous AR expression was sufficient for androgen-dependent transcription of AR target genes in prostate basal epithelial cells, but did not exert a positive feedback on endogenous AR expression. Treatment of basal prostate epithelial cells with inhibitors of epigenetic gene silencing was not efficient in

  11. Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary.

    Science.gov (United States)

    Dewailly, Didier; Robin, Geoffroy; Peigne, Maëliss; Decanter, Christine; Pigny, Pascal; Catteau-Jonard, Sophie

    2016-11-01

    Androgens, FSH, anti-Müllerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science. During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the

  12. Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men.

    Science.gov (United States)

    Manuck, Stephen B; Marsland, Anna L; Flory, Janine D; Gorka, Adam; Ferrell, Robert E; Hariri, Ahmad R

    2010-01-01

    In studies employing functional magnetic resonance imaging (fMRI), reactivity of the amygdala to threat-related sensory cues (viz., facial displays of negative emotion) has been found to correlate positively with interindividual variability in testosterone levels of women and young men and to increase on acute administration of exogenous testosterone. Many of the biological actions of testosterone are mediated by intracellular androgen receptors (ARs), which exert transcriptional control of androgen-dependent genes and are expressed in various regions of the brain, including the amygdala. Transactivation potential of the AR decreases (yielding relative androgen insensitivity) with expansion a polyglutamine stretch in the N-terminal domain of the AR protein, as encoded by a trinucleotide (CAG) repeat polymorphism in exon 1 of the X-chromosome AR gene. Here we examined whether amygdala reactivity to threat-related facial expressions (fear, anger) differs as a function of AR CAG length variation and endogenous (salivary) testosterone in a mid-life sample of 41 healthy men (mean age=45.6 years, range: 34-54 years; CAG repeats, range: 19-29). Testosterone correlated inversely with participant age (r=-0.39, p=0.012) and positively with number of CAG repeats (r=0.45, p=0.003). In partial correlations adjusted for testosterone level, reactivity in the ventral amygdala was lowest among men with largest number of CAG repeats. This inverse association was seen in both the right (r(p)=-0.34, pleft (r(p)=-0.32, pdifferences in salivary testosterone, also in right (r=0.40, pleft (r=0.32, pdifferences in salivary testosterone also predicted dorsal amygdala reactivity and did so independently of CAG repeats, it is suggested that androgenic influences within this anatomically distinct region may be mediated, in part, by non-genomic or AR-independent mechanisms.

  13. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society.

    Science.gov (United States)

    Wild, Robert A; Carmina, Enrico; Diamanti-Kandarakis, Evanthia; Dokras, Anuja; Escobar-Morreale, Hector F; Futterweit, Walter; Lobo, Rogerio; Norman, Robert J; Talbott, Evelyn; Dumesic, Daniel A

    2010-05-01

    Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. An expert panel in PCOS and CVD reviewed literature and presented recommendations. Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.

  14. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  15. Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/β cell ratio and subsequent insulin secretion.

    Science.gov (United States)

    Ramaswamy, S; Grace, C; Mattei, A A; Siemienowicz, K; Brownlee, W; MacCallum, J; McNeilly, A S; Duncan, W C; Rae, M T

    2016-06-06

    Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P = 0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P = 0.001), sustained into adolescence (P = 0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P = 0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P = 0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P = 0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells.

  16. Insensitive Enough Semantics

    Directory of Open Access Journals (Sweden)

    Richard Vallée

    2006-06-01

    Full Text Available According to some philosophers, sentences like (1 “It is raining” and (2 “John is ready” are context sensitive sentences even if they do not contain indexicals or demonstratives. That view initiated a context sensitivity frenzy. Cappelen and Lepore (2005 summarize the frenzy by the slogan “Every sentence is context sensitive” (Insensitive Semantics, p. 6, note 5. They suggest a view they call Minimalism according to which the truth conditions of utterances of sentences like (1/(2 are exactly what Convention T gives you. I will distinguish different propositions, and refocus semantics on sentences. As distinct from what the protagonists in the ongoing debate think, I argue that the content or truth conditions of utterances of both context sensitive sentences and sentences like (1/(2 are not interesting from a semantic point of view, and that the problem sentences like (1/(2 raises is not about context sensitivity or context insensitivity of sentences, but relevance of the content of utterances.

  17. Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun

    2014-01-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conse......Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity...... is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved...... in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls...

  18. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete’s urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as ‘T-equivalent’ concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact. PMID:26998755

  19. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.

  20. A novel method to demonstrate that pregnant women with polycystic ovary syndrome hyper-expose their fetus to androgens as a possible stepping stone for the developmental theory of PCOS. A pilot study.

    Science.gov (United States)

    Homburg, Roy; Gudi, Anil; Shah, Amit; M Layton, Alison

    2017-08-08

    Polycystic ovary syndrome (PCOS), whose aetiology is unknown, is predominately a familial syndrome but confirmation of candidate genes has proved elusive. The developmental hypothesis for the origin of PCOS suggests that exposure of the fetus to excess androgens influences imprinting, leading to altered genetic expression in adult life. The aim of this pilot study was to examine whether the female fetus of a mother with PCOS is indeed exposed to excess androgens. Using sebum production in the newborn as a surrogate for exposure to excess androgens during pregnancy thisprospective case control studyexamined whether neonatal sebum excretion is greater in female infants born to PCOS mothers compared to non-PCOS. Women with known PCOS (all 3 Rotterdam criteria) (n = 9) and non-PCOS controls (n = 12), with a female fetus, were recruited at 24 weeks pregnancy and serum testosterone estimated. Sebum was measured using Sebutape® for 30 and 60 min within 24 h of birth, at 1 week, 4-6 weeks and 6 months after birth in both mother and child. Sebum excretion was measured in mother and child in the same site at each time frame and consistently. All semi-quantitative sebum excretion estimations were compared (t-test) between the two groups and correlated with testosterone concentrations during pregnancy. In this pilot study, 21 women completed the 6 month examination period (PCOS group (n = 9) and controls (n = 12). Mean testosterone was 6.2 nmol/L (normal PCOS mothers and 2.75 nmol/L in controls at 24 weeks pregnancy. At all time frames, the results of sebum excretion at 30 and 60 min were consistent. The sebum excretion of mothers in both groups was fairly constant from birth throughout 6 months. All babies were born between 37 and 41 weeks gestational age. Six of nine newborns had detectable sebum excretion at birth in the PCOS mothers group compared to 1 of 12 in the controls (P = 0.01). These results suggest that women with PCOS could hyper

  1. Cotargeting of Androgen Synthesis and Androgen Receptor Expression as a Novel Treatment for Castration Resistant Prostate Cancer

    Science.gov (United States)

    2017-08-01

    disease [2-4]. The major mechanism underlying the development of CRPC is the reactivation of the androgen receptor (AR), the driver of prostate cancer ...Epigenetic Activator of Androgen Receptor Expression in Castration- Resistant Prostate Cancer . Indiana Basic Urological Research (IBUR) Symposium...principal discipline(s) of the project? Androgen receptor (AR) is the driver of prostate cancer development and progression and is the validated

  2. High androgen levels protect against hypothyroidism.

    Science.gov (United States)

    Schmidt, Johanna; Dahlgren, Eva; Bryman, Inger; Berntorp, Kerstin; Trimpou, Penelope; Wilhelmsen, Lars; Landin-Wilhelmsen, Kerstin

    2017-01-01

    Hypothyroidism is a common disorder, appearing mainly in women although less frequently found in women with polycystic ovary syndrome (PCOS). The objective was to test the hypothesis that hyperandrogenism might protect against hypothyroidism. The data from three prospective follow-up studies (up to 21 years) and one register study were compared: women with PCOS (Rotterdam criteria), n = 25, women with Turner syndrome, n = 217, a random population sample of women, n = 315, and men, n = 95 (the WHO MONICA study). Findings were to be verified or rejected in all females, n = 553 716, from the same region. The proportion of hypothyroidism was calculated and thyroid peroxidase antibodies (TPO) in serum were measured. Hypothyroidism at >50 years of age was found in 8% of women with PCOS, 4% in men (PCOS vs. men; ns), 43% of women with Turner syndrome, irrespective of karyotype (p Hypothyroidism increased with age in all groups except PCOS women and men. In the register study, hypothyroidism was less common in women with PCOS >25 years (5.5%) than in women without PCOS (6.8%) from the same region (p Hypothyroidism was less frequently seen in women with PCOS and in men compared with women in the general population and among women with Turner syndrome. This was not explained by altered autoimmunity or the Y-chromosome. Androgens seem to protect against hypothyroidism. © 2016 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

    Science.gov (United States)

    Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

    2017-04-01

    Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

  4. Hirsutism, Acne, and Hair Loss: Management of Hyperandrogenic Cutaneous Manifestations of Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Cenk Yasa

    2017-08-01

    Full Text Available PPolycystic ovary syndrome is the most common endocrine abnormality that affects reproductive-aged women. Diagnostic criteria of polycystic ovary syndrome have been established by different societies in recent years, and hyperandrogenism remains as one of the main criteria for diagnosis. Cutaneous manifestations of hyperandrogenism include hirsutism, acne and androgenic alopecia and are commonly observed in women with polycystic ovary syndrome. The major determinants of cutaneous manifestations are increased production of androgen and increased tissue availability. Cutaneous manifestations of hyperandrogenism are cosmetic problems, which produce significant emotional distress and psychological morbidity. Treatment includes a combination of combined oral contraceptives, antiandrogens, insulin sensitizers, gonadotropin releasing hormone agonists, topical medications, and cosmetic procedures. The diagnosis, management, and treatment approaches are described in detail in this review.

  5. Morbidade hospitalar por ingestão de esteroides anabólico-androgênicos (EAA no Brasil Hospital morbidity due to anabolic-androgenic steroids (AAS consumption in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Henrique Almeida da Silva Junior

    2013-04-01

    ária de 15-29 anos possuíram as maiores taxas no período estudado.INTRODUCTION: Anabolic androgenic steroids (AAS are male sex hormones, developers and maintainers of sexual characteristics associated with masculinity and the anabolic status of somatic tissues. The physical and mental effects of AAS abuse are rare and it is almost impossible to say with certainty what adverse effects may become evident after their self-administration; however, they constitute risk of death for the individuals. OBJECTIVE: The aim of this study was to describe the main characteristics of morbidity by AAS ingestion in Brazil in the 2000/2010 period. METHODS: Information on hospitalizations was obtained from computerized databases of the Ministry of Health. In the analysis of AAS consumption as primary or secondary diagnosis for hospital admission, the E28.1 (androgen excess, E34.5 (androgen insensitivity syndrome, T38.7 (adverse effect of and underdosing of androgens and anabolic congeners and Y42.7 (adverse effects in the therapeutic use of androgens and anabolic congeners codes of the ICD-10 were used. RESULTS: Hospitalizations by AAS were responsible for 0.001% of total admissions in the country. 1,319 admissions (mean = 119.9, SD = 99.01 were accounted. The Androgen insensitivity syndrome was the primary cause, corresponding to 55.8% of total admissions. Of of all hospitalizations, 1% of patients died and the maximum stay was of 47 days (mean = 3.8, SD = 4.7. Minas Gerais, Maranhão and Espírito Santo presented the highest rates of hospital admissions per 1,000,000 inhabitants from 2002 to 2007. Women and people aged 15-29 presented the highest hospitalization rate 82.5% and 37.7%, respectively. CONCLUSION: The results of this study showed that the hospitalization rate was relatively low for AAS intake; women and individuals aged 15-29 years possessed the highest rates in the period studied.

  6. Women's Health Implications of Polycystic Ovary Syndrome

    NARCIS (Netherlands)

    Veltman-Verhulst, S.M.

    2012-01-01

    Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of unknown etiology which affects approximately 12% of women. Principal features of PCOS are anovulation resulting in irregular or absent menstruation, excessive androgens (male sex hormones) and ovaries with multiple follicles

  7. Voluntary Exercise Improves Estrous Cyclicity in Prenatally Androgenized Female Mice Despite Programming Decreased Voluntary Exercise: Implications for Polycystic Ovary Syndrome (PCOS).

    Science.gov (United States)

    Homa, Lori D; Burger, Laura L; Cuttitta, Ashley J; Michele, Daniel E; Moenter, Suzanne M

    2015-12-01

    Prenatal androgen (PNA) exposure in mice produces a phenotype resembling lean polycystic ovary syndrome. We studied effects of voluntary exercise on metabolic and reproductive parameters in PNA vs vehicle (VEH)-treated mice. Mice (8 wk of age) were housed individually and estrous cycles monitored. At 10 weeks of age, mice were divided into groups (PNA, PNA-run, VEH, VEH-run, n = 8-9/group); those in the running groups received wheels allowing voluntary running. Unexpectedly, PNA mice ran less distance than VEH mice; ovariectomy eliminated this difference. In ovary-intact mice, there was no difference in glucose tolerance, lower limb muscle fiber types, weight, or body composition among groups after 16 weeks of running, although some mitochondrial proteins were mildly up-regulated by exercise in PNA mice. Before running, estrous cycles in PNA mice were disrupted with most days in diestrus. There was no change in cycles during weeks 1-6 of running (10-15 wk of age). In contrast, from weeks 11 to 16 of running, cycles in PNA mice improved with more days in proestrus and estrus and fewer in diestrus. PNA programs reduced voluntary exercise, perhaps mediated in part by ovarian secretions. Exercise without weight loss improved estrous cycles, which if translated could be important for fertility in and counseling of lean women with polycystic ovary syndrome.

  8. Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

    2015-03-01

    Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

  9. The promotion on cell growth of androgen-dependent prostate cancer by antimony via mimicking androgen activity.

    Science.gov (United States)

    Zhang, Changwen; Li, Penghao; Wen, Yingwu; Feng, Guowei; Liu, Yu; Zhang, Yangyi; Xu, Yong; Zhang, Zhihong

    2018-05-15

    Antimony is a widely used heavier pnictogens in industry, and its toxicity has been a matter of concern. Although previous studies have suggested that antimony may have the function as either a tumor suppressor or an oncogene in several cancers, the molecular basis underlying antimony-mediated transformation is still unclear. In the current study, we attempt to elucidate the potential role of antimony in the development of prostate cancer. Our results showed that the concentration of antimony was much higher in serum of prostate cancer patients, and was closely associated with poor outcome of patients who underwent radical prostatectomy. Additionally, low dose of antimony could promote proliferation and invasion of androgen-dependent prostate cancer cell line LNCaP cells in vitro and in vivo. The mechanistic studies demonstrated that exposure to antimony triggered the phosphorylation of androgen receptor (AR), which transcriptionally regulates the expression of androgen-related targets, including PSA and NKX3.1. Overall, our results unearthed that antimony could promote tumor growth by mimicking androgen activity in androgen-dependent prostate cancer cells. Therefore, these findings expanded our understanding on the molecular mechanism of antimony in tumorigenesis and tumor progression of prostate cancer, and it appears to be an inspiring strategy to restrain prostate cancer by inhibiting antimony-induced androgen-like effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. A polarization-insensitive plasmonic photoconductive terahertz emitter

    KAUST Repository

    Li, Xurong

    2017-11-16

    We present a polarization-insensitive plasmonic photoconductive terahertz emitter that uses a two-dimensional array of nanoscale cross-shaped apertures as the plasmonic contact electrodes. The geometry of the cross-shaped apertures is set to maximize optical pump absorption in close proximity to the contact electrodes. The two-dimensional symmetry of the cross-shaped apertures offers a polarization-insensitive interaction between the plasmonic contact electrodes and optical pump beam. We experimentally demonstrate a polarization-insensitive terahertz radiation from the presented emitter in response to a femtosecond optical pump beam and similar terahertz radiation powers compared to previously demonstrated polarization-sensitive photoconductive emitters with plasmonic contact electrode gratings at the optimum optical pump polarization.

  11. Prenatal and adult androgen activities in alcohol dependence.

    Science.gov (United States)

    Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

    2017-07-01

    Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Punishment Insensitivity in Early Childhood: A Developmental, Dimensional Approach.

    Science.gov (United States)

    Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S

    2015-08-01

    Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.

  13. Vitamin D, PCOS and androgens in men: a systematic review

    Directory of Open Access Journals (Sweden)

    Christian Trummer

    2018-03-01

    Full Text Available Background: Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders. Aim: The aim of this review was to provide an overview on the effects of vitamin D on polycystic ovary syndrome (PCOS in women and androgen metabolism in men. Methods: We performed a systematic literature search in PubMed for relevant English language publications published from January 2012 until September 2017. Results and discussion: The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues of women and men. In women, vitamin D status has been associated with several features of PCOS. In detail, cross-sectional data suggest a regulatory role of vitamin D in PCOS-related aspects such as ovulatory dysfunction, insulin resistance as well as hyperandrogenism. Moreover, results from randomized controlled trials (RCTs suggest that vitamin D supplementation may be beneficial for metabolic, endocrine and fertility aspects in PCOS. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels. Conclusion: In summary, vitamin D deficiency is associated with adverse fertility outcomes including PCOS and hypogonadism, but the evidence is insufficient to establish causality. High-quality RCTs are needed to further evaluate the effects of vitamin D supplementation in PCOS women as well as on androgen levels in men.

  14. Prenatal androgen excess programs metabolic derangements in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Dai, Xiaonan; Wang, Jing; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2013-04-01

    Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.

  15. Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma.

    LENUS (Irish Health Repository)

    Dennedy, Michael Conall

    2012-02-01

    Approximately 7% of women of reproductive age manifest polycystic ovary syndrome (PCOS) and <0.5% have other causes of hyperandrogenism including congenital adrenal hyperplasia (CAH), androgen-secreting tumour of an ovary or an adrenal gland, Cushing\\'s syndrome or hyperthecosis. The presence of features atypical of PCOS should prompt more extensive evaluation than that usually undertaken. Features atypical of PCOS include the onset of symptoms outside the decade of 15-25 years, rapid progression of symptoms, the development of virilization and a serum testosterone concentration in excess of twice the upper limit of the reference range. Ethnic background, family history and specific clinical findings, e.g. Cushingoid appearance, may inform a focused investigation. Otherwise, patients should have measurement of 17-hydroxyprogesterone (17-OHP) under basal conditions ideally in the early morning, and if abnormal, they should have measurement of 17-OHP one hour after the administration of synthetic ACTH, 250 microg i.v., to screen for CAH, which is present in approximately 2% of hyperandrogenic patients. The overnight cortisol suppression test employing 1 mg dexamethasone at midnight is a sensitive test for Cushing\\'s syndrome. Coronal tomographic (CT) scanning of the adrenals and transvaginal ultrasonography of the ovaries are the investigations of choice when screening for tumours in these organs. Less frequently required is catheterization and sampling from both adrenal and ovarian veins, which is a technically demanding procedure with potential complications which may provide definitive diagnostic information not available from other investigations. Illustrative case reports highlight some complexities in the investigation of hyperandrogenic patients presenting with features atypical of PCOS and include only the ninth case report of an androgen-secreting ovarian teratoma.

  16. Cardiometabolic Aspects of the Polycystic Ovary Syndrome

    OpenAIRE

    Randeva, Harpal S.; Tan, Bee K.; Weickert, Martin O.; Lois, Konstantinos; Nestler, John E.; Sattar, Naveed; Lehnert, Hendrik

    2012-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age and is associated with various metabolic perturbations, in addition to chronic anovulation and factors related to androgen excess. In general, women live longer than men and develop cardiovascular disease at an older age. However, women with PCOS, as compared with age- and body mass index-matched women without the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinem...

  17. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

    Science.gov (United States)

    Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

    2015-11-01

    Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

    Science.gov (United States)

    Manti, Maria; Fornes, Romina; Qi, Xiaojuan; Folmerz, Elin; Lindén Hirschberg, Angelica; de Castro Barbosa, Thais; Maliqueo, Manuel; Benrick, Anna; Stener-Victorin, Elisabet

    2018-03-22

    Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

  19. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Kumar, Ashim; Woods, Keslie S; Bartolucci, Alfred A; Azziz, Ricardo

    2005-06-01

    To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age- and race-specific normative values. Cross-sectional observational study. One hundred and eight-two (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited. Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma. The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White women with PCOS. The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.

  20. The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

    DEFF Research Database (Denmark)

    Lucas-herald, A.; Bertelloni, S.; Juul, A.

    2016-01-01

    = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. CONCLUSIONS: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T...

  1. Hypochlorite Oxidation of Select Androgenic Steroids

    Science.gov (United States)

    Steroid hormones are vital for regulation of various biological functions including sexual development. Elevated concentrations of natural and synthetic androgenic steroids have been shown to adversely affect normal development in indigenous aqueous species. Androgens and their s...

  2. Androgenic alopecia; the risk–benefit ratio of Finasteride

    Directory of Open Access Journals (Sweden)

    David L. Rowland

    2018-04-01

    Full Text Available Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset, several concerns appeared over time regarding the frequency and magnitude of finasteride adverse effects, which in some cases seem to be even irreversible. This paper presents administration of finasteride in androgenic alopecia from two distinct perspectives. On one hand, androgenic alopecia is a condition that affects especially the self-image and esteem, aspects that are subjective, namely changeable and thus relative. On the other hand, this condition presents a multifactorial etiology, androgens being only in part involved. In addition, androgens have their own physiological roles within the body, so that any androgenic suppression should be carefully advised. Yet, adverse effects induced by Finasteride are only in part documented and treatable. Finally, alternative therapeutic approaches (like topical finasteride become available, so that the oral administration of Finasteride for androgenic alopecia should be in our opinion reevaluated. As a conclusion, a very detailed and informed discussion should take place with such patients accepting to start a therapy with finasteride for androgenic alopecia.

  3. Modulation of Androgen Receptor Transcriptional Activity

    NARCIS (Netherlands)

    H.Y. Wong (Hao Yun)

    2009-01-01

    textabstractAndrogens, testosterone (T) and 5a-dihydrotestosterone (DHT), are important for male and female physiology, in particular for male sexual differentiation, development of secondary male characteristics and spermatogenesis. These hormones exert their actions by binding to the androgen

  4. Insensitive detonator apparatus for initiating large failure diameter explosives

    Science.gov (United States)

    Perry, III, William Leroy

    2015-07-28

    A munition according to a preferred embodiment can include a detonator system having a detonator that is selectively coupled to a microwave source that functions to selectively prime, activate, initiate, and/or sensitize an insensitive explosive material for detonation. The preferred detonator can include an explosive cavity having a barrier within which an insensitive explosive material is disposed and a waveguide coupled to the explosive cavity. The preferred system can further include a microwave source coupled to the waveguide such that microwaves enter the explosive cavity and impinge on the insensitive explosive material to sensitize the explosive material for detonation. In use the preferred embodiments permit the deployment and use of munitions that are maintained in an insensitive state until the actual time of use, thereby substantially preventing unauthorized or unintended detonation thereof.

  5. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    Science.gov (United States)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

  6. Root Formation in Ethylene-Insensitive Plants1

    Science.gov (United States)

    Clark, David G.; Gubrium, Erika K.; Barrett, James E.; Nell, Terril A.; Klee, Harry J.

    1999-01-01

    Experiments with ethylene-insensitive tomato (Lycopersicon esculentum) and petunia (Petunia × hybrida) plants were conducted to determine if normal or adventitious root formation is affected by ethylene insensitivity. Ethylene-insensitive Never ripe (NR) tomato plants produced more belowground root mass but fewer aboveground adventitious roots than wild-type Pearson plants. Applied auxin (indole-3-butyric acid) increased adventitious root formation on vegetative stem cuttings of wild-type plants but had little or no effect on rooting of NR plants. Reduced adventitious root formation was also observed in ethylene-insensitive transgenic petunia plants. Applied 1-aminocyclopropane-1-carboxylic acid increased adventitious root formation on vegetative stem cuttings from NR and wild-type plants, but NR cuttings produced fewer adventitious roots than wild-type cuttings. These data suggest that the promotive effect of auxin on adventitious rooting is influenced by ethylene responsiveness. Seedling root growth of tomato in response to mechanical impedance was also influenced by ethylene sensitivity. Ninety-six percent of wild-type seedlings germinated and grown on sand for 7 d grew normal roots into the medium, whereas 47% of NR seedlings displayed elongated taproots, shortened hypocotyls, and did not penetrate the medium. These data indicate that ethylene has a critical role in various responses of roots to environmental stimuli. PMID:10482660

  7. Androgens as double-edged swords: Induction and suppression of follicular development.

    Science.gov (United States)

    Pan, Jie-Xue; Zhang, Jun-Yu; Ke, Zhang-Hong; Wang, Fang-Fang; Barry, John A; Hardiman, Paul J; Qu, Fan

    2015-01-01

    Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

  8. Androgens regulate gene expression in avian skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Matthew J Fuxjager

    Full Text Available Circulating androgens in adult reproductively active male vertebrates influence a diversity of organ systems and thus are considered costly. Recently, we obtained evidence that androgen receptors (AR are expressed in several skeletal muscles of three passeriform birds, the golden-collared manakin (Manacus vitellinus, zebra finch (Taenopygia guttata, and ochre-bellied flycatcher (Mionectes oleagieus. Because skeletal muscles that control wing movement make up the bulk of a bird's body mass, evidence for widespread effects of androgen action on these muscles would greatly expand the functional impact of androgens beyond their well-characterized effects on relatively discrete targets throughout the avian body. To investigate this issue, we use quantitative PCR (qPCR to determine if androgens alter gene mRNA expression patterns in wing musculature of wild golden-collared manakins and captive zebra finches. In manakins, the androgen testosterone (T up-regulated expression of parvalbumin (PV and insulin-like growth factor I (IGF-I, two genes whose products enhance cellular Ca(2+ cycling and hypertrophy of skeletal muscle fibers. In T-treated zebra finches, the anti-androgen flutamide blunted PV and IGF-I expression. These results suggest that certain transcriptional effects of androgen action via AR are conserved in passerine skeletal muscle tissue. When we examined wing muscles of manakins, zebra finches and ochre-bellied flycatchers, we found that expression of PV and IGF-I varied across species and in a manner consistent with a function for AR-dependent gene regulation. Together, these findings imply that androgens have the potential to act on avian muscle in a way that may enhance the physicality required for successful reproduction.

  9. Inhibition of progression of androgen-dependent prostate LNCaP tumors to androgen independence in SCID mice by oral caffeine and voluntary exercise.

    Science.gov (United States)

    Zheng, Xi; Cui, Xiao-Xing; Huang, Mou-Tuan; Liu, Yue; Wagner, George C; Lin, Yong; Shih, Weichung Joe; Lee, Mao-Jung; Yang, Chung S; Conney, Allan H

    2012-01-01

    The effect of oral caffeine or voluntary running wheel exercise (RW) alone or in combination on the progression of human androgen-dependent LNCaP prostate tumors to androgen independence in male severe combined immunodeficiency mice was determined. The mice were injected subcutaneously with LNCaP cells, and when the tumors reached a moderate size, the mice were surgically castrated and treated with caffeine (0.40 mg/ml drinking water) or RW alone or in combination for 42 days. We found that caffeine administration or RW inhibited the progression and growth of androgen-dependent LNCaP tumors to androgen independence, and a combination of the 2 regimens was more effective than the individual regimens alone. The ratios of the percent mitotic cells/caspase-3 positive cells in tumors from the caffeine-treated, RW-treated, or combination-treated mice were decreased by 34%, 38%, and 52%, respectively. Caffeine treatment increased the percentage of mitotic tumor cells undergoing apoptosis (lethal mitosis) whereas RW inhibited the increase in interleukin-6 that occurred during the progression of LNCaP tumors from androgen dependence to androgen independence. Our results indicate that oral administration of caffeine in combination with voluntary exercise may be an effective strategy for the prevention of prostate cancer progression from androgen dependence to androgen independence.

  10. Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats.

    Science.gov (United States)

    Mishra, Jay S; More, Amar S; Kumar, Sathish

    2018-01-22

    Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test. DHT females had no change in islet number, size and beta cell proliferation/apoptosis but exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased mtDNA copy number, increased reactive oxygen production and downregulation of mitochondrial biogenesis) and enhanced glucose-stimulated insulin secretion. Ins expression was increased in DHT islets. In vitro incubation of control islets with DHT dose-dependently stimulated Ins transcription. Analysis of Ins1 gene revealed a putative androgen responsive element in the promoter. Chromatin-immunoprecipitation assays showed that androgen receptors bind to this element in response to DHT stimulation. Furthermore, reporter assays showed that the promoter element is highly responsive to androgens. Insulin stimulated glucose uptake in skeletal muscle was decreased with associated decrease in IRβ expression in DHT females. Our studies identified a novel androgen-mediated mechanism for the control of Ins expression via transcriptional regulation providing a molecular mechanism linking elevated androgens and hyperinsulemia. Decreased IRβ expression in the skeletal muscles may contribute, in part, to glucose intolerance in this model. © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of

  11. The postfinasteride syndrome; an overview

    Directory of Open Access Journals (Sweden)

    David L. Rowland

    2016-10-01

    Full Text Available As a 5-α reductase inhibitor, Finasteride has proven effective in ameliorating two conditions documented to be androgen dependent, namely male androgenic alopecia and benign prostatic hyperplasia. Therapeutic results are maintained as long as the drug is administered, with treatment cessation generally leading to the return of symptomatology for each condition. In addition, during the therapeutic phase, several adverse effects have been reported, some of which persist long or indefinitely after treatment cessation, known as “post-finasteride syndrome.” Herein we present and discuss the most common finasteride side effects, along with a psycho-neuroendocrine rationale that could explain the persistence of many adverse effects after treatment cessation. Moreover, we argue that finasteride adverse effects occurring during finasteride administration should be delineated from postfinasteride side effects (encountered after treatment cessation, suggesting the need to be addressed separately within a therapeutic perspective. Until a tailored therapeutic approach of postfinasteride syndrome becomes available, we have noted that hand preference and sexual orientation seem to be useful as possible predicting factors for finasteride side effects and postfinasteride syndrome. Finally, even though finasteride administration is considered relatively safe, literature data urges prudence. Specifically, recent studies report that some subjects receiving finasteride develop severe depressive episodes including suicidal thoughts, in part due to persistent sexual side effects.

  12. Micropenis

    Directory of Open Access Journals (Sweden)

    Semra Çetinkaya

    2009-01-01

    Full Text Available Micropenis refers to an extremely small penis with a stretched penile length of less than 2.5 SD below the mean for age or stage of sexual development. It should be differentiated from a buried or hidden penis and pe-nile agenesis. It is important to use a standard technique of stretched penile measurement and nomograms for age to identify children with micropenis. Based on etiol-ogy they can be classified as hypogonadotropic hypo-gonadism (hypothalamic or pituitary failure, hypergo-nadotropic hypogonadism (testicular failure, androgen insensitivity syndrome and idiopathic groups.

  13. Expression of anti-Müllerian hormone during normal and pathological gonadal development

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Jørgensen, N; Graem, N

    1999-01-01

    an inhibitory effect on AMH. However, in adolescent boys lacking germ cells because of cancer treatment and in a majority of infertile adult men with idiopathic germ cell aplasia, AMH expression was also down-regulated despite the complete lack of spermatogenesis. The decrease in AMH expression thus reflects...... expression of AMH was observed in a 20-yr-old 46,XY female with androgen insensitivity syndrome, who retained prepubertal testicular morphology. In normal testes, the switch-off of AMH expression was usually associated with the appearance of primary spermatocytes, suggesting that their presence had...

  14. Care of women with XY karyotype

    DEFF Research Database (Denmark)

    Jorgensen, Pernille Bach; Kjartansdóttir, Kristín Rós; Fedder, Jens

    2010-01-01

    OUTCOME MEASURE(S): Evaluation of etiology, diagnosis, treatment, and associated disorders in XY women. RESULT(S): Many gene mutations can cause abnormal fetal development leading to androgen insensitivity syndrome or gonadal dysgenesis disorders. Females with these disorders have an XY karyotype but look...... like girls. They are mostly diagnosed at puberty, and the condition will often lead to serious psychological problems. Increased risk of malignancies and problems with pregnancy and infertility are other aspects that should be considered. This guideline will aid doctors in caring for XY females...

  15. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

    Science.gov (United States)

    Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

    2013-11-01

    Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

  16. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    Directory of Open Access Journals (Sweden)

    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There is a high prevalence of diabetes mellitus (DM and dyslipidemia in women with polycystic ovary syndrome (PCOS. The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C, n = 10; the andronate-treated group (Andronate, n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks; and the andronate-treated and high-fat diet group (Andronate+HFD, n = 10. The rate of glucose appearance (Ra of glucose, gluconeogenesis (GNG, and the rate of glycerol appearance (Ra of glycerol were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P P Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

  17. Molecular mechanisms of androgen receptor functions

    NARCIS (Netherlands)

    K. Steketee (Karine)

    2007-01-01

    textabstractThe androgens testosterone (T) and dihydrotestosterone (DHT) are steroid hormones, which are necessary for development and maintenance of the functions of the male sex organs, including the prostate. Androgens also play an important role in benign abnormalities of the prostate and in the

  18. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    International Nuclear Information System (INIS)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-01-01

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  19. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  20. Compounds from Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.

    Science.gov (United States)

    Wang, Xueni; Tao, Rui; Yang, Jing; Miao, Lin; Wang, Yu; Munyangaju, Jose Edouard; Wichai, Nuttapong; Wang, Hong; Zhu, Yan; Liu, Erwei; Chang, Yanxu; Gao, Xiumei

    2017-01-01

    To investigate the phytoestrogenic and phytoandrogenic activities of compounds isolated from CS and uncover the role of CS in prevention of oestrogen/androgen-induced BPH. Cells were treated with CS compounds, and immunofluorescence assay was performed to detect the nuclear translocation of ER α or AR in MCF-7 or LNCaP cells; luciferase reporter assay was performed to detect ERs or AR transcriptional activity in HeLa or AD293 cells; MTT assay was performed to detect the cell proliferation of MCF-7 or LNCaP cells. Oestrogen/androgen-induced BPH model was established in rat and the anti-BPH, anti-estrogenic, and anti-androgenic activities of CS in vivo were further investigated. The nuclear translocation of ER α was stimulated by nine CS compounds, three of which also stimulated AR translocation. The transcriptional activities of ER α and ER β were induced by five compounds, within which only ECG induced AR transcriptional activity as well. Besides, ECG stimulated the proliferation of both MCF-7 cells and LNCaP cells. CS extract suppressed oestrogen/androgen-induced BPH progress in vivo by downregulation of E2 and T level in serum and alteration of the expressions of ER α , ER β , and AR in the prostate. Our data demonstrates that compounds from CS exhibit phytoestrogenic and phytoandrogenic activities, which may contribute to inhibiting the oestrogen/androgen-induced BPH development.

  1. Genetic investigation into ethnic disparity in polycystic ovarian syndrome

    DEFF Research Database (Denmark)

    Li, Shuxia; Zhu, Dongyi; Duan, Hongmei

    2013-01-01

    Polycystic ovarian syndrome is universally the most common endocrinopathy in women of reproductive age. It is characterized by composite clinical phenotypes reflecting the reproductive impact of ovarian dysfunction (androgen excess, oligo-/anovulation, polycystic ovary) and metabolic abnormalities...... more efficient strategies for treatment and prevention of polycystic ovarian syndrome....... to unravel the molecular basis of the interethnic difference in the pathogenesis of the syndrome. It is hoped that identification and characterization of population-specific structural genetic and functional genomic patterns could help to not only deepen our understanding of the aetiology but also develop...

  2. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

    National Research Council Canada - National Science Library

    Wiren, Kristine M; Jepsen, Karl

    2006-01-01

    .... We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone...

  3. Alteration in follistatin gene expression detected in prenatally androgenized rats.

    Science.gov (United States)

    Salehi Jahromi, Marziyeh; Ramezani Tehrani, Fahimeh; Hill, Jennifer W; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

    2017-06-01

    Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.

  4. Further Evaluation of Androgen Therapy In Aplastic Anemia: With Special Reference to Correlation Between Response to Androgen and EEI

    International Nuclear Information System (INIS)

    Whang, Kee Suk

    1967-01-01

    Patients with aplastic anemia were treated with a combination of depo-testosterone cyclopentylpropionate (Upjohn) and dexamethasone. In 7 of 15 patients treated, there was response in which either a significant increase in hemoglobin concentration, a prolonged interval or a cessation of blood transfusion requirement developed during androgen therapy. Younger patients with cellular marrow appeared to be better responding to androgen. EEI (Effective Erythropoietic Index) formulated by Gardner and Nathan (1966) which was a helpful measurement as to whether patients with myelofibrosis would response to androgen, was evaluated in patients with aplastic anemia. It was concluded that EEI as well as ferrokinetics indices (Plasma- 59 Fe-disappearance rate, RBC 59 Fe net incorporation) did not significantly correlate with the degree of response to androgen in aplastic anemia.

  5. Office blood pressure, ambulatory blood pressure monitoring, and echocardiographic abnormalities in women with polycystic ovary syndrome: role of obesity and androgen excess.

    Science.gov (United States)

    Luque-Ramírez, Manuel; Martí, David; Fernández-Durán, Elena; Alpañés, Macarena; Álvarez-Blasco, Francisco; Escobar-Morreale, Héctor F

    2014-03-01

    Whether or not blood pressure (BP) and heart function of women with polycystic ovary syndrome (PCOS) are altered remains unclear, albeit subtle abnormalities in the regulation of BP observed in these women might suggest a mild masculinization of their cardiovascular system. To study the influence of obesity and androgen excess on BP and echocardiographic profiles of women with the syndrome, we conducted a cross-sectional case-control study comparing office and ambulatory BP monitoring, as well as echocardiographic assessments, in 63 premenopausal women with the classic phenotype, 33 nonhyperandrogenic women with regular menses, and 25 young men. Forty-nine subjects were lean and 72 had weight excess (body mass index ≥25 kg/m(2)). Participants had no previous history of hypertension and were nonsmokers. Men showed the highest BP readings, and the lowest readings were observed in control women, whereas women with PCOS had intermediate values. Undiagnosed hypertension was more common in subjects with weight excess irrespective of sex and hyperandrogenism. Women with PCOS and weight excess showed frequencies of previously undiagnosed hypertension that were similar to those of men with weight excess and higher than those observed in nonhyperandrogenic women. Lastly, male sex, weight excess and hypertension, the latter in men as well as in women with PCOS, increased left ventricular wall thickness. In summary, our results show that patients with classic PCOS and weight excess frequently have undiagnosed BP abnormalities, leading to target organ damage.

  6. Pharmacodynamics of selective androgen receptor modulators.

    Science.gov (United States)

    Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

    2003-03-01

    The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

  7. Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

    Directory of Open Access Journals (Sweden)

    Mario Amore

    2012-01-01

    Full Text Available The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM and on the potential benefits of testosterone (T treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths.

  8. Discovery and therapeutic promise of selective androgen receptor modulators.

    Science.gov (United States)

    Chen, Jiyun; Kim, Juhyun; Dalton, James T

    2005-06-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

  9. Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

    Science.gov (United States)

    Daan, N M P; Jaspers, L; Koster, M P H; Broekmans, F J M; de Rijke, Y B; Franco, O H; Laven, J S E; Kavousi, M; Fauser, B C J M

    2015-10-01

    Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1-2.8)], after adjustment for age, ethnicity, smoking and BMI (P cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research

  10. Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome

    OpenAIRE

    Montezuma, Thais; Ant?nio, Fl?via Ign?cio; de S? Rosa e Silva, Ana Carolina Japur; de S?, Marcos Felipe Silva; Ferriani, Rui Alberto; Ferreira, Cristine Homsi Jorge

    2011-01-01

    OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18- to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University...

  11. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome ...

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  12. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

    2015-05-01

    To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation

  13. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, Andrea; Iaquinto, Gaetano; Gluud, Christian

    2002-01-01

    The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease.......The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease....

  14. Further Evaluation of Androgen Therapy In Aplastic Anemia: With Special Reference to Correlation Between Response to Androgen and EEI

    Energy Technology Data Exchange (ETDEWEB)

    Whang, Kee Suk [Kyungpook National University School of Medicine, Deagu (Korea, Republic of)

    1967-03-15

    Patients with aplastic anemia were treated with a combination of depo-testosterone cyclopentylpropionate (Upjohn) and dexamethasone. In 7 of 15 patients treated, there was response in which either a significant increase in hemoglobin concentration, a prolonged interval or a cessation of blood transfusion requirement developed during androgen therapy. Younger patients with cellular marrow appeared to be better responding to androgen. EEI (Effective Erythropoietic Index) formulated by Gardner and Nathan (1966) which was a helpful measurement as to whether patients with myelofibrosis would response to androgen, was evaluated in patients with aplastic anemia. It was concluded that EEI as well as ferrokinetics indices (Plasma-{sup 59}Fe-disappearance rate, RBC {sup 59}Fe net incorporation) did not significantly correlate with the degree of response to androgen in aplastic anemia.

  15. Developmental Programming: Prenatal and Postnatal Androgen Antagonist and Insulin Sensitizer Interventions Prevent Advancement of Puberty and Improve LH Surge Dynamics in Prenatal Testosterone-Treated Sheep.

    Science.gov (United States)

    Padmanabhan, Vasantha; Veiga-Lopez, Almudena; Herkimer, Carol; Abi Salloum, Bachir; Moeller, Jacob; Beckett, Evan; Sreedharan, Rohit

    2015-07-01

    Prenatal T excess induces maternal hyperinsulinemia, early puberty, and reproductive/metabolic defects in the female similar to those seen in women with polycystic ovary syndrome. This study addressed the organizational/activational role of androgens and insulin in programming pubertal advancement and periovulatory LH surge defects. Treatment groups included the following: 1) control; 2) prenatal T; 3) prenatal T plus prenatal androgen antagonist, flutamide; 4) prenatal T plus prenatal insulin sensitizer, rosiglitazone; 5) prenatal T and postnatal flutamide; 6) prenatal T and postnatal rosiglitazone; and 7) prenatal T and postnatal metformin. Prenatal treatments spanned 30-90 days of gestation and postnatal treatments began at approximately 8 weeks of age and continued throughout. Blood samples were taken twice weekly, beginning at approximately 12 weeks of age to time puberty. Two-hour samples after the synchronization with prostaglandin F2α were taken for 120 hours to characterize LH surge dynamics at 7 and 19 months of age. Prenatal T females entered puberty earlier than controls, and all interventions prevented this advancement. Prenatal T reduced the percentage of animals having LH surge, and females that presented LH surge exhibited delayed timing and dampened amplitude of the LH surge. Prenatal androgen antagonist, but not other interventions, restored LH surges without normalizing the timing of the surge. Normalization of pubertal timing with prenatal/postnatal androgen antagonist and insulin sensitizer interventions suggests that pubertal advancement is programmed by androgenic actions of T involving insulin as a mediary. Restoration of LH surges by cotreatment with androgen antagonist supports androgenic programming at the organizational level.

  16. Evolution of the androgen-induced male phenotype.

    Science.gov (United States)

    Fuxjager, Matthew J; Miles, Meredith C; Schlinger, Barney A

    2018-01-01

    The masculine reproductive phenotype varies significantly across vertebrates. As a result, biologists have long recognized that many of the mechanisms that support these phenotypes-particularly the androgenic system-is evolutionarily labile, and thus susceptible to the effects of selection for different traits. However, exactly how androgenic signaling systems vary in a way which results in dramatically different functional outputs, remain largely unclear. We explore this topic here by outlining four key-but non-mutually exclusive-hypotheses that propose how the mechanisms of androgenic signaling might change over time to potentiate the emergence of phenotypical variation in masculine behavior and physiology. We anchor this framework in a review of our own studies of a tropical bird called the golden-collared manakin (Manacus vitellinus), which has evolved an exaggerated acrobatic courtship display that is heavily androgen-dependent. The result is an example of how the cellular basis of androgenic action can be modified to support a unique reproductive repertoire. We end this review by highlighting a broad pathway forward to further pursue the intricate ways by which the mechanisms of hormone action evolve to support processes of adaptation and animal design.

  17. Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

    Science.gov (United States)

    Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

    2010-01-01

    Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

  18. Effect of propofol on androgen receptor activity in prostate cancer cells.

    Science.gov (United States)

    Tatsumi, Kenichiro; Hirotsu, Akiko; Daijo, Hiroki; Matsuyama, Tomonori; Terada, Naoki; Tanaka, Tomoharu

    2017-08-15

    Androgen receptor is a nuclear receptor and transcription factor activated by androgenic hormones. Androgen receptor activity plays a pivotal role in the development and progression of prostate cancer. Although accumulating evidence suggests that general anesthetics, including opioids, affect cancer cell growth and impact patient prognosis, the effect of those drugs on androgen receptor in prostate cancer is not clear. The purpose of this study was to investigate the effect of the general anesthetic propofol on androgen receptor activity in prostate cancer cells. An androgen-dependent human prostate cancer cell line (LNCaP) was stimulated with dihydrotestosterone (DHT) and exposed to propofol. The induction of androgen receptor target genes was investigated using real-time reverse transcription polymerase chain reaction, and androgen receptor protein levels and localization patterns were analyzed using immunoblotting and immunofluorescence assays. The effect of propofol on the proliferation of LNCaP cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Propofol significantly inhibited DHT-induced expression of androgen receptor target genes in a dose- and time-dependent manner, and immunoblotting and immunofluorescence assays indicated that propofol suppressed nuclear levels of androgen receptor proteins. Exposure to propofol for 24h suppressed the proliferation of LNCaP cells, whereas 4h of exposure did not exert significant effects. Together, our results indicate that propofol suppresses nuclear androgen receptor protein levels, and inhibits androgen receptor transcriptional activity and proliferation in LNCaP cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity.

    Science.gov (United States)

    Shapiro, Lucy; Chatterjee, Sumana; Ramadan, Dina G; Davies, Kate M; Savage, Martin O; Metherell, Louise A; Storr, Helen L

    2017-12-01

    GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown. To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect. We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS. A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver-Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in FANCA and PHKB in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect. Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres. © 2017 European Society of Endocrinology.

  20. Polycystic ovarian syndrome: clinical and biological diagnosis.

    Science.gov (United States)

    Bachelot, Anne

    2016-12-01

    Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. This syndrome leads to clinical hyperandrogenism and/or a biological dysovulation and infertility. Its diagnosis is based on consensual diagnostic criteria, but which are likely to change in the near future with the rise of the interest of new markers such as AMH. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. The exact etiology of PCOS is unknown and is likely multifactorial. Many studies indicate that PCOS results from originally ovarian abnormalities. In some patients, secondary hyperinsulinemia with insulin resistance plays a role in the pathophysiology. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject.

  1. Androgen receptor polyglutamine repeat length (AR-CAGn) modulates the effect of testosterone on androgen-associated somatic traits in Filipino young adult men.

    Science.gov (United States)

    Ryan, Calen P; Georgiev, Alexander V; McDade, Thomas W; Gettler, Lee T; Eisenberg, Dan T A; Rzhetskaya, Margarita; Agustin, Sonny S; Hayes, M Geoffrey; Kuzawa, Christopher W

    2017-06-01

    The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels. We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines (n = 675). When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn (p AR-CAGn was associated with an increase in these same somatic traits. Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations. © 2017 Wiley Periodicals, Inc.

  2. Evaluative Conditioning is Insensitive to Blocking

    Directory of Open Access Journals (Sweden)

    Tom Beckers

    2009-01-01

    Full Text Available Evaluative conditioning has been claimed to have a number of functional characteristics that set it apart from other forms of associative learning in humans, such as insensitivity to extinction and contingency, independence of contingency awareness, and insensitivity to modulation. Despite its potential theoretical importance, until now few data are available concerning the susceptibility of evaluative conditioning to cue competition effects such as blocking. In the present study, we assessed the susceptibility of acquired preferences and evaluations to blocking in a candy game. Results suggest that evaluative conditioning is not susceptible to blocking. We discuss this observation in the light of theoretical accounts of evaluative conditioning and associative learning in humans.

  3. Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

    Science.gov (United States)

    Hu, Jieping; Wang, Gongxian; Sun, Ting

    2017-05-01

    Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

  4. Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor

    Science.gov (United States)

    Abi Ghanem, Charly; Degerny, Cindy; Hussain, Rashad; Liere, Philippe; Pianos, Antoine; Tourpin, Sophie; Habert, René; Schumacher, Michael

    2017-01-01

    The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis. PMID:29107990

  5. Critical androgen-sensitive periods of rat penis and clitoris development

    OpenAIRE

    Welsh, M.; Macleod, D. J.; Walker, M.; Smith, L. B.; Sharpe, R. M.

    2010-01-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during t...

  6. Androgen receptor and histone lysine demethylases in ovine placenta.

    Directory of Open Access Journals (Sweden)

    Ellane R Cleys

    Full Text Available Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR. Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.

  7. Unraveling the Complexities of Androgen Receptor Signaling in Prostate Cancer Cells

    OpenAIRE

    Heemers, Hannelore V.; Tindall, Donald J.

    2009-01-01

    Androgen signaling is critical for proliferation of prostate cancer cells but cannot be fully inhibited by current androgen deprivation therapies. A study by Xu et al. in this issue of Cancer Cell provides insights into the complexities of androgen signaling in prostate cancer and suggests avenues to target a subset of androgen-sensitive genes.

  8. Role of Androgen Receptor in Growth of Androgen Independent Prostate Cancer

    National Research Council Canada - National Science Library

    Chen, Charlie

    2003-01-01

    ...) overexpression is the only consistent change in the progression of prostate cancer. In the last grand period, I confirmed by western blot analysis that androgen receptor protein is higher in HR than HS tumors...

  9. High androgens in postmenopausal women and the risk for atherosclerosis and cardiovascular disease: the Rotterdam Study.

    Science.gov (United States)

    Meun, Cindy; Franco, Oscar H; Dhana, Klodian; Jaspers, Loes; Muka, Taulant; Louwers, Yvonne; Ikram, M Arfan; Fauser, Bart C J M; Kavousi, Maryam; Laven, Joop S E

    2018-02-01

    Polycystic ovary syndrome (PCOS) is closely linked to hyperandrogenism. In PCOS, hyperandrogenism has been associated with metabolic disturbances which increase the risk for cardiovascular disease (CVD). To assess the association of high serum androgen levels, as a postmenopausal remnant of PCOS, with the prevalence of atherosclerosis and incidence of CVD in postmenopausal women. The Rotterdam Study, a prospective population-based cohort study. Median follow up was 11.36 years. General community. 2578 women aged over 55. Exclusion criteria were missing informed consent or follow-up data, perimenopausal status, menopause by surgical intervention or at an unnatural age (age 62). None. Linear, logistic, and cox regression models assessed the association of top quartiles (P75) of serum testosterone, free androgen index (FAI), dehydroepiandrosterone, and androstenedione and SHBG with coronary artery calcium, carotid intima media thickness (IMT), pulse wave velocity, peripheral artery disease and incidence of coronary heart disease, stroke, and CVD. Mean age (standard deviation) was 70.19 (8.71) years and average time since menopause 19.85 (9.94) years. Highest quartile FAI was associated with higher pulse wave velocity [β (95%CI): 0.009 (0.000;0.018)]. Highest quartile dehydroepiandrosterone [β (95%CI): -0.008 (-0.015;-0.001)] and androstenedione [β (95%CI): -0.010 (-0.017;-0.003)] levels were associated with a lower IMT. We found no association between high androgen levels and incident stroke, coronary heart disease, or cardiovascular disease. Postmenopausal high androgen levels were not associated with an increased risk for CVD. Cardiovascular health in women with PCOS might be better than was anticipated. Copyright © 2018 Endocrine Society

  10. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome.

    Science.gov (United States)

    Baskind, N Ellissa; Balen, Adam H

    2016-11-01

    Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous disorder linked with disturbances of reproductive, endocrine and metabolic function. The definition and aetiological hypotheses of PCOS are continually developing to incorporate evolving evidence of the syndrome, which appears to be both multifactorial and polygenic. The pathophysiology of PCOS encompasses inherent ovarian dysfunction that is strongly influenced by external factors including the hypothalamic-pituitary axis and hyperinsulinaemia. Neuroendocrine abnormalities including increased gonadotrophin-releasing hormone (GnRH) pulse frequency with consequent hypersecretion of luteinising hormone (LH) affects ovarian androgen synthesis, folliculogenesis and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the gonadotrophin abnormalities, and there is emerging evidence putatively implicating dysfunction of the Kiss 1 system. Within the follicle subunit itself, there are intra-ovarian paracrine modulators, cytokines and growth factors, which appear to play a role. Adrenally derived androgens may also contribute to the pathogenesis of PCOS, but their role is less defined. Copyright © 2016. Published by Elsevier Ltd.

  11. Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

    OpenAIRE

    Redig, Amanda J.; Munshi, Hidayatullah G.

    2010-01-01

    Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

  12. MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease.

    Science.gov (United States)

    Schiffer, Lina; Kempegowda, Punith; Arlt, Wiebke; O'Reilly, Michael W

    2017-09-01

    Female androgen excess and male androgen deficiency manifest with an overlapping adverse metabolic phenotype, including abdominal obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease and an increased risk of cardiovascular disease. Here, we review the impact of androgens on metabolic target tissues in an attempt to unravel the complex mechanistic links with metabolic dysfunction; we also evaluate clinical studies examining the associations between metabolic disease and disorders of androgen metabolism in men and women. We conceptualise that an equilibrium between androgen effects on adipose tissue and skeletal muscle underpins the metabolic phenotype observed in female androgen excess and male androgen deficiency. Androgens induce adipose tissue dysfunction, with effects on lipid metabolism, insulin resistance and fat mass expansion, while anabolic effects on skeletal muscle may confer metabolic benefits. We hypothesise that serum androgen concentrations observed in female androgen excess and male hypogonadism are metabolically disadvantageous, promoting adipose and liver lipid accumulation, central fat mass expansion and insulin resistance. © 2017 The authors.

  13. Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Jørgensen, N; Müller, Jørn

    1996-01-01

    conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects...... expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c-kit expression in subjects with disorders...

  14. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, E; Jørgensen, N

    1998-01-01

    , including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress...... in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...

  15. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    Science.gov (United States)

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  16. Searching for the variables that control human rule-governed "insensitivity".

    Science.gov (United States)

    Fox, Adam E; Kyonka, Elizabeth G E

    2017-09-01

    Verbal rules or instructions often exert obvious and meaningful control over human behavior. Sometimes instructions benefit the individual by enabling faster acquisition of a skill or by obviating an aversive consequence. However, research has also suggested a clear disadvantage: "insensitivity" to changing underlying contingencies. The two experiments described here investigated the variables that control initial rule-following behavior and rule-following insensitivity. When the initial rule was inaccurate, behavior was consistent with the rule for approximately half of participants and all participants' behavior was mostly insensitive to changing contingencies. When the initial rule was accurate, behavior of all participants was consistent with it and behavior for nearly all participants was insensitive to changes in underlying contingencies. These findings have implications for how best to establish and maintain rule-following behavior in applied settings when deviant behavior would be more reinforcing to the individual. © 2017 Society for the Experimental Analysis of Behavior.

  17. [Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

    Science.gov (United States)

    Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

    2013-01-20

    The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

  18. Variation of luteinizing hormone and androgens in oligomenorrhoea and its implications for the study of polycystic ovary syndrome

    NARCIS (Netherlands)

    van Hooff, M. H.; van der Meer, M.; Lambalk, C. B.; Schoemaker, J.

    1999-01-01

    We measured luteinizing hormone (LH) and androgen concentrations in patients at different phases of the oligomenorrhoeic cycle and compared the results with those of patients with normogonadotrophic amenorrhoea. Several blood samples separated by >/=7 days were obtained from each of 72 patients with

  19. Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth

    International Nuclear Information System (INIS)

    Liu, Shicheng; Yuan, Yiming; Okumura, Yutaka; Shinkai, Norihiro; Yamauchi, Hitoshi

    2010-01-01

    The androgen receptor (AR) is the main therapeutic target for treatment of metastatic prostate cancers. The present study demonstrates that the topoisomerase I inhibitor camptothecin selectively inhibits androgen-responsive growth of prostate cancer cells. Camptothecin strikingly inhibited mutated and wild-type AR protein expression in LNCaP and PC-3/AR cells. This inhibition coincided with decreased androgen-mediated AR phosphorylation at Ser 81 and reduced androgen-mediated AR transcriptional activity in a dose-dependent manner. Additionally, camptothecin disrupted the association between AR and heat shock protein 90 and impeded binding of the synthetic androgen [ 3 H]R1881 to AR in LNCaP cells. Camptothecin also blocked androgen-induced AR nuclear translocation, leading to downregulation of the AR target gene PSA. In addition to decreasing the intracellular and secreted prostate-specific antigen (PSA) levels, camptothecin markedly inhibited androgen-stimulated PSA promoter activity. Collectively, our data reveal that camptothecin not only serves as a traditional genotoxic agent but, by virtue of its ability to target and disrupt AR, may also be a novel candidate for the treatment of prostate cancer.

  20. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2004-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  1. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2005-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  2. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2003-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  3. ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE

    Science.gov (United States)

    Within the last ten years, awareness has grown about environmental chemicals that display antiandrogenic or androgenic activity. While studies in the early 1990s focused on pesticides that acted as androgen receptor (AR) antagonists, it soon became evident that this was not the ...

  4. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2006-01-01

    .... Intermittent androgen ablation therapy (IAAT) may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  5. Obstetrical complications in dichorionic twin pregnancies in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Jonsdottir, Fjola; Nilas, Lisbeth; Andreasen, Kirsten R

    2017-01-01

    INTRODUCTION: Both women with polycystic ovary syndrome (PCOS) and women with twin pregnancies have increased risk of adverse pregnancy outcome. The aim of this study was to investigate the impact of PCOS and maternal androgen levels on the outcome of dichorionic twin pregnancy. MATERIAL...

  6. Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

    Science.gov (United States)

    Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C

    2017-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

  7. Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Yoda, Tomomi; McNamara, Keely May; Miki, Yasuhiro; Takagi, Mayu; Rai, Yoshiaki; Ohi, Yasuyo; Sagara, Yasuaki; Tamaki, Kentaro; Hirakawa, Hisashi; Ishida, Takanori; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2014-11-01

    Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  8. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

    Science.gov (United States)

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-11-01

    Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism

  9. Novel growth hormone receptor mutation in a Chinese patient with Laron syndrome.

    Science.gov (United States)

    Hui, Hamilton N T; Metherell, Louise A; Ng, K L; Savage, Martin O; Camacho-Hübner, Cecilia; Clark, Adrian J L

    2005-02-01

    Laron syndrome, growth hormone (GH) insensitivity syndrome, caused by a mutation of the GH receptor (GHR) gene, is extremely rare in the Chinese population. We report a Chinese girl diagnosed with Laron syndrome at age 1.9 years with height -4.9 SDS, basal GH 344 mIU/ml, IGF-I <12 ng/ml, IGFBP-3 <0.2 mg/ml, and undetectable GHBP. A novel mutation of the GHR, not previously described, was identified at the donor splice site of intron 6.

  10. Anesthetic management of a patient with Bartter’s syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Harun Aydoğan

    2012-09-01

    Full Text Available Bartter’s syndrome is a rare disorder characterized bysevere hypochloremic metabolic alkalosis, hypokalemia,hyponatremia, hyperaldosteronism, elevation in plasmarenin activity and insensitivity to angiotensin II. Electrolyteimbalances such as hypomagnesemia, hyponatremiamight make anesthetic management difficult in Barttersyndrome. A 4 years old patient underwent surgery foringuinal hernia with caudal anesthesia using bupivacaine0.25%. In this case report, it was aimed to discuss the anestheticmanagement of a patient with Bartter syndrome.Key words: Regional anesthesia, Bartter syndrome, inguinalhernia surgery, pediatric anesthesia

  11. Androgenic anabolic steroids also impair right ventricular function.

    Science.gov (United States)

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  12. Dry eye syndrome. Etiological and therapeutic aspects.

    Science.gov (United States)

    Apostol, Silvia; Filip, M; Dragne, Carmen; Filip, A

    2003-01-01

    "Dry eye syndrome" is a common disorder of the tear film that results from inadequate tear production, excessive tear evaporation or abnormality in mucin or lipid components of the tear film. A number of 53 patients suffering from dry eye syndrome were followed up for a period of 18 months. The study group was heterogeneous, including a lot of conditions accompanied by dry eye syndrome: Syogren's syndrome, lupus erythematous, ocular rosacea, patients with systemic treatments with antidepressants, betablockers, diuretics, oral contraceptives, glaucomatous patients with topical beta-blockers, postmenopausal women, aging people, computer users and long-term contact lens wearers. The therapeutical options were dictated by the severity of the syndrome: substitution therapy, treatment of the underlying eyelid diseases, modifying of the environmental conditions and treatment of the complications in the most severe cases. The new pathological approach is innovative and it may provide a real therapeutical measure for this condition: topical A Cyclosporine and androgen drops.

  13. Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor

    NARCIS (Netherlands)

    Blankvoort, B.M.G.; Groene, E.M. de; Meeteren-Kreikamp, A.P. van; Witkamp, R.F.; Rodenburg, R.J.T.; Aarts, J.M.M.J.G.

    2001-01-01

    The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2

  14. Expression of matrix metalloproteinases and ovarian morphological changes in androgenized cyclic female guinea pigs.

    Science.gov (United States)

    Li, Jun-rong; Shen, Ting; Wang, Yan-li; Wei, Quan-wei; Shi, Fang-xiong

    2016-02-01

    This study was conducted to investigate expression of matrix metalloproteinases (MMPs) and ovarian morphological changes in androgenized cyclic female guinea pigs. Adult cyclic female guinea pigs were injected daily for 28 days with medium doses of testosterone propionate (TP; 1 mg/100g), high doses of TP (2 mg/100g), or saline (control). Serum concentrations of testosterone, estradiol (E2), and progesterone (P4) were measured. Histologic sections of ovaries were stained with hematoxylin-eosin and by immunohistochemistry. Expressions of steroidogenic acute regulatory protein, proliferating cell nuclear antigen, and MMP-2 and MMP-9 in the ovary were characterized by immunohistochemistry. After 28 days of TP injection, serum testosterone concentrations were increased dose-dependently. An appropriate dosage of TP could induce permanent anovulation in guinea pigs, making them a potential model for human polycystic ovary syndrome. MMP-2 and MMP-9 are jointly involved in the growth and atresia of ovarian follicles in cyclic guinea pigs. Increased numbers of atretic antral follicles in the ovary might be associated with the observed high expression of MMP-2 in androgenized cyclic guinea pigs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  16. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Iaquinto, G; Gluud, C

    2003-01-01

    Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  17. Microarray analysis of androgen-regulated gene expression in testis: the use of the androgen-binding protein (ABP-transgenic mouse as a model

    Directory of Open Access Journals (Sweden)

    Grossman Gail

    2005-12-01

    Full Text Available Abstract Background Spermatogenesis is an androgen-dependent process, yet the molecular mechanisms of androgens' actions in testis are poorly understood. Transgenic mice overexpressing rat androgen-binding protein (ABP in their testes have reduced levels of intratesticular androgens and, as a result, show a progressive impairment of spermatogenesis. We used this model to characterize changes in global gene expression in testis in response to reduced bioavailability of androgens. Methods Total RNA was extracted from testes of 30-day old transgenic and wild-type control mice, converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays. Microarray results were confirmed by real-time reverse transcription polymerase chain reaction. Results Three-hundred-eighty-one genes (3.05% of all transcripts represented on the chips were up-regulated and 198 genes (1.59% were down-regulated by at least a factor of 2 in the androgen-deficient animals compared to controls. Genes encoding membrane proteins, intracellular signaling molecules, enzymes, proteins participating in the immune response, and those involved in cytoskeleton organization were significantly overrepresented in the up-regulated group. Among the down-regulated transcripts, those coding for extracellular proteins were overrepresented most dramatically, followed by those related to proteolysis, cell adhesion, immune response, and growth factor, cytokine, and ion channel activities. Transcripts with the greatest potential impact on cellular activities included several transcription factors, intracellular signal transducers, secreted signaling molecules and enzymes, and various cell surface molecules. Major nodes in the up-regulated network were IL-6, AGT, MYC, and A2M, those in the down-regulated network were IL-2, -4, and -10, MAPK8, SOCS1, and CREB1. Conclusion Microarray analysis followed by gene ontology profiling and connectivity analysis identified several functional

  18. Polycystic ovary syndrome.

    Science.gov (United States)

    Azziz, Ricardo; Carmina, Enrico; Chen, ZiJiang; Dunaif, Andrea; Laven, Joop S E; Legro, Richard S; Lizneva, Daria; Natterson-Horowtiz, Barbara; Teede, Helena J; Yildiz, Bulent O

    2016-08-11

    Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.

  19. Identification of a Novel Androgen Receptor Mutation in a Family With Multiple Components Compatible With the Testicular Dysgenesis Syndrome

    DEFF Research Database (Denmark)

    Lottrup, Grete; Jørgensen, Anne; Nielsen, John E.

    2013-01-01

    showed features consistent with insufficient testis development and TDS.Conclusion: The presence of all hallmarks of TDS, including germ cell cancer, in a family with a novel AR mutation causing a partial decrease in AR function is in line with the concept that reduced androgen signaling may contribute......, cryptorchidism, hypospadias, and testicular cancer, caused by a novel AR mutation.Objective: The aim of this study was to describe the phenotype of the affected males, characterize functionally the novel AR mutation, and discuss the significance of partial androgen insufficiency in the pathogenesis of TDS...... analysis of the mutation in a gene-reporter assay showed a 50% reduction in AR-induced transcriptional activity. The affected males had elevated LH and T in accordance with decreased AR signaling. The histology and immunohistochemical profile of the testis tissue from the 2 patients with testicular cancer...

  20. Anti-androgen effects of cypermethrin on the amino- and carboxyl-terminal interaction of the androgen receptor

    International Nuclear Information System (INIS)

    Hu, Jin-xia; Li, Yan-fang; Pan, Chen; Zhang, Jin-peng; Wang, Hong-mei; Li, Jing; Xu, Li-chun

    2012-01-01

    Graphical abstract: Both the known AR antagonist nilutamide and the pyrethroid insecticide cypermethrin inhibited DHT-induced AR N/C interaction in the mammalian two-hybrid assay. However, cypermethrin was a weaker androgen antagonist than nilutamide. Highlights: ► We have developed the mammalian two-hybrid assay. ► The assay displayed appropriate response to DHT and nilutamide. ► The N/C interaction was induced by DHT in a dose-dependent manner. ► Nilutamide inhibited DHT-induced AR N/C interaction. ► Cypermethrin exhibits inhibitory effects on DHT-induced AR N/C interaction. -- Abstract: The pyrethroid insecticide, cypermethrin has been demonstrated to be an environmental anti-androgen in the androgen receptor (AR) reporter gene assay. The amino- and carboxyl-terminal (N/C) interaction is required for transcription potential of the AR. In order to characterize the anti-androgen effects of cypermethrin involved in the N/C interaction of AR, the mammalian two-hybrid assay has been developed in the study. The fusion vectors pVP16-ARNTD, pM-ARLBD and the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The assay displayed appropriate response to the potent, classical AR agonist 5α-dihydrotestosterone (DHT) and known AR antagonist nilutamide. The N/C interaction was induced by DHT from 10 −11 M to 10 −5 M in a dose-dependent manner. Nilutamide did not activate N/C interaction, while inhibited DHT-induced AR N/C interaction at the concentrations from 10 −7 M to 10 −5 M. Treatment of CV-1 cells with cypermethrin alone did not activate the reporter CAT. Cypermethrin significantly decreased the DHT-induced reporter CAT expression at the higher concentration of 10 −5 M. The mammalian two-hybrid assay provides a promising tool both for defining mechanism involved in AR N/C interaction of EDCs and for screening of chemicals with androgen agonistic and antagonistic activities. Cypermethrin exhibits inhibitory effects on the DHT-induced AR N

  1. Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome

    NARCIS (Netherlands)

    L.A. Menke (Leonie); T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); G.R.J. Zandwijken (Gladys); M.A.J. de Ridder (Maria); R.J.H. Odink (Roelof); M. Jansen (Maarten); H.A. de Delemarre-van Waal (Henriëtte); W.H. Stokvis-Brantsma; J.J.J. Waelkens (Johan); C. Westerlaken (Ciska); H.M. Reeser (Maarten); A.S.P. van Trotsenburg (Paul); E.F. Gevers (Evelien); S. van Buuren (Stef); P.H. Dejonckere (Philippe); A.C.S. Hokken-Koelega (Anita); B.J. Otten (Barto); J.M. Wit (Jan)

    2010-01-01

    textabstractContext and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed

  2. Pure Androgen-Secreting Adrenal Adenoma Associated with Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2013-01-01

    Full Text Available Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed.

  3. Munitions having an insensitive detonator system for initiating large failure diameter explosives

    Science.gov (United States)

    Perry, III, William Leroy

    2015-08-04

    A munition according to a preferred embodiment can include a detonator system having a detonator that is selectively coupled to a microwave source that functions to selectively prime, activate, initiate, and/or sensitize an insensitive explosive material for detonation. The preferred detonator can include an explosive cavity having a barrier within which an insensitive explosive material is disposed and a waveguide coupled to the explosive cavity. The preferred system can further include a microwave source coupled to the waveguide such that microwaves enter the explosive cavity and impinge on the insensitive explosive material to sensitize the explosive material for detonation. In use the preferred embodiments permit the deployment and use of munitions that are maintained in an insensitive state until the actual time of use, thereby substantially preventing unauthorized or unintended detonation thereof.

  4. A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

    Science.gov (United States)

    Vehof, Jelle; Hysi, Pirro G; Hammond, Christopher J

    2017-04-01

    To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. Cross-sectional association study. A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5

  5. Does polycystic ovary syndrome affect cognition? : A functional magnetic resonance imaging study exploring working memory

    NARCIS (Netherlands)

    Soleman, Remi S; Kreukels, Baudewijntje P C; Veltman, Dick J; Cohen-Kettenis, Peggy T; Hompes, Peter G A; Drent, Madeleine L; Lambalk, Cornelis B

    OBJECTIVE: To study effects of overexposure to androgens and subsequent antiandrogenic treatment on brain activity during working memory processes in women with polycystic ovary syndrome (PCOS). DESIGN: In this longitudinal study, working memory function was evaluated with the use of functional

  6. Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Kornreich, L; Horev, G; Schwarz, M; Karmazyn, B; Laron, Z

    2002-04-01

    To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

  7. Photonic crystal based polarization insensitive flat lens

    International Nuclear Information System (INIS)

    Turduev, M; Bor, E; Kurt, H

    2017-01-01

    The paper proposes a new design of an inhomogeneous artificially created photonic crystal lens structure consisting of annular dielectric rods to efficiently focus both transverse electric and transverse magnetic polarizations of light into the same focal point. The locations of each individual cell that contains the annular dielectric rods are determined according to a nonlinear distribution function. The inner and outer radii of the annular photonic dielectric rods are optimized with respect to the polarization insensitive frequency response of the transmission spectrum of the lens structure. The physical background of the polarization insensitive focusing mechanism is investigated in both spatial and frequency domains. Moreover, polarization independent wavefront transformation/focusing has been explored in detail by investigating the dispersion relation of the structure. Corresponding phase index distribution of the lens is attained for polarization insensitive normalized frequency range of a / λ   =  0.280 and a / λ   =  0.300, where a denotes the lattice constant of the designed structure and λ denotes the wavelength of the incident light. We show the wave transformation performance and focal point movement dynamics for both polarizations of the lens structure by specially adjusting the length of the structure. The 3D finite-difference time domain numerical analysis is also performed to verifiy that the proposed design is able to focus the wave regardless of polarization into approximately the same focal point (difference between focal distances of both polarizations stays below 0.25 λ ) with an operating bandwidth of 4.30% between 1476 nm and 1541 nm at telecom wavelengths. The main superiorities of the proposed lens structure are being all dielectric and compact, and having flat front and back surfaces, rendering the proposed lens design more practical in the photonic integration process in various applications such as optical switch

  8. The Relationship between Androgenic Alopecia and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ghasem Rahmatpour Rokni

    2016-07-01

    Full Text Available Prostate cancer (PC and Androgenic Alopecia (AGA i are both common diseases in elder men. It seems that androgen plays a crucial role in the growth and development of prostate cancer. Therefore, the current study intended to investigate the relationship between androgenic alopecia and prostate cancer. The present study is a case-control study conducted on 75 patients with prostate cancer (case group referring to Imam Khomeini Hospital in Sari, Iran. The case group was compared with the control group (75 healthy individuals. The intended questionnaire of the study included information such as the age, sex, duration of disease, stage of disease, level of PSA, time diagnosis and time of interview for all the participants. The results of interview and clinical examination along with the patient’s information all were filled in the questionnaire and were statistically analyzed by SPSS after data collection. The mean age of PC group and healthy group was respectively 69.08 ± 8.97 and 68 .45 ± 10.16 years. The average level of PSA was 10.86 ± 11.7 and 2.66 ± 2.7 ng/ml in PC and healthy group in turn. The average duration of cancer was 12.63 ± 9.19 months in PC group. Furthermore, about 6.7% of cancer patients were in stage I, 48% were stage II, 29.3% were in stage III and 16% were in stage IV of prostate cancer. Besides, the number of cancer patients who had both frontal and vertex alopecia (baldness altogether exceeded healthy individuals (P=0.002. According to the results of the present study, there was a significant relationship between prostate cancer and androgenic alopecia which might have been caused by the effect of androgens on both diseases. Consequently, androgenic alopecia can be considered as one of the risk factors associated with prostate cancer.

  9. Gingival fibromatosis with hypertrichosis syndrome: Case series of rare syndrome

    Directory of Open Access Journals (Sweden)

    Preetha Balaji

    2017-01-01

    Full Text Available Gingival fibromatosis with hypertrichosis syndrome is an extremely rare genetic condition characterized by profound overgrowth of hair and gums, as well as other variable features. Gingival fibromatosis is characterized by a large increase in the gingival dimension which extends above the dental crowns, covering them partially or completely. They were found to have a genetic origin, may also occur in isolation or be part of a syndrome, or acquired origin, due to specific drugs administered systemically. Congenital generalized hypertrichosis is a heterogeneous group of diseases with continuing excessive growth of terminal hair without androgenic stimulation. It has informally been called werewolf syndrome because the appearance is similar to that of a werewolf. Various syndromes have been associated with these features such as epilepsy, mental retardation, cardiomegaly, or osteochondrodysplasia. As so far very few cases have been reported in literature, we are reporting a series of three cases with management of the same. The excess gingival tissues, in these cases, were removed by conventional gingivectomy under general anesthesia. The postoperative result was uneventful and the patient's appearance improved significantly. Good esthetic result was achieved to allow patient to practice oral hygiene measures. Though this is not a serious condition clinically, psychosocial trauma cannot be neglected owing to the cosmetic disfigurement it produces.

  10. Cardiotoxic effects of cocaine and anabolic-androgenic steroids in the athlete.

    Science.gov (United States)

    Welder, A A; Melchert, R B

    1993-04-01

    Cocaine and anabolic-androgenic steroid abuse have become major drug problems in the United States. Cocaine has been designated as "the drug of greatest national health concern" while as many as 1 million Americans have used or are currently using anabolic-androgenic steroids to promote athletic performance and/or improve physical appearance. Unfavorable cardiovascular events have been linked to both cocaine and anabolic-androgenic steroid abuse in healthy, physically active individuals. Deaths of several United States athletes in 1986 focused attention on the life-threatening cardiovascular consequences of cocaine abuse. Reports of myocardial injury with anabolic-androgenic steroid abuse are anecdotal. Nevertheless, case reports have illustrated the alarming cardiotoxic potential of these steroids in athletes. Anabolic-androgenic steroids were correlated to myocardial infarction in weight lifters and cardiomyopathy in a former professional football player. From the total emergency room episodes where cocaine was mentioned in 1990, approximately 66% of these episodes occurred in young individuals 18-29 years of age. Over 500,000 of the individuals currently taking anabolic-androgenic steroids for nonmedical purposes are high-school children. Because cocaine and anabolic-androgenic steroids are used improperly, more focus needs to be paid to the toxic mechanisms of their adverse effects. Therefore, the purpose of this review is to discuss mechanisms whereby exercise and/or exercise training may alter the cardiovascular responses to these drugs. Furthermore, we would like to illustrate that contrary to the popular belief, acute and chronic abuse of cocaine and anabolic-androgenic steroids have a negative impact on exercise performance.

  11. Efficacy and Safety of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome

    NARCIS (Netherlands)

    Menke, Leonie A.; Sas, Theo C. J.; de Muinck Keizer-Schrama, Sabine M. P. F.; Zandwijken, Gladys R. J.; de Ridder, Maria A. J.; Odink, Roelof J.; Jansen, Maarten; Delemarre-van de Waal, Henriëtte A.; Stokvis-Brantsma, Wilhelmina H.; Waelkens, Johan J.; Westerlaken, Ciska; Reeser, H. Maarten; Paul van Trotsenburg, A. S.; Gevers, Evelien F.; van Buuren, Stef; Dejonckere, Philippe H.; Hokken-Koelega, Anita C. S.; Otten, Barto J.; Wit, Jan M.

    2010-01-01

    Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10

  12. Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Muinck Keizer de - Schrama, S.M.P.F.; Zandwijken, G.R.J.; Ridder, M.A.J. de; Odink, R.J.; Jansen, M.; Delemarre de - Waal, H.A. van; Stokvis-Brantsma, W.H.; Waelkens, J.J.; Westerlaken, C.; Reeser, H.M.; Trotsenburg, A.S.P. van; Gevers, E.F.; Buuren, S. van; Dejonckere, P.H.; Hokken-Koelega, A.C.S.; Otten, B.J.; Wit, J.M.

    2010-01-01

    Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10

  13. Efficacy and Safety of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome

    NARCIS (Netherlands)

    Menke, Leonie A.; Sas, Theo C. J.; Keizer-Schrama, Sabine M. P. F. de Muinck; Zandwijken, Gladys R. J.; de Ridder, Maria A. J.; Odink, Roelof J.; Jansen, Maarten; Delemarre-van de Waal, Henriette A.; Stokvis-Brantsma, Wilhelmina H.; Waelkens, Johan J.; Westerlaken, Ciska; Reeser, H. Maarten; van Trotsenburg, A. S. Paul; Gevers, Evelien F.; van Buuren, Stef; DeJonckere, Philippe H.; Hokken-Koelega, Anita C. S.; Otten, Barto J.; Wit, Jan M.

    Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10

  14. Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome.

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Muinck Keizer-Schrama, S.M.P.F. de; Zandwijken, G.R.; Ridder, M.A. de; Odink, R.J.; Jansen, M.; Delemarre-van de Waal, H.A.; Stokvis-Brantsma, W.H.; Waelkens, J.J.; Westerlaken, C.; Reeser, H.M.; Trotsenburg, A.S. van; Gevers, E.F.; Buuren, S. van; Dejonckere, P.H.; Hokken-Koelega, A.C.S.; Otten, B.J.; Wit, J.M.

    2010-01-01

    Context and Objective: GH therapy increases growth and adult height in Turner syndrome (TS). The benefit to risk ratio of adding the weak androgen oxandrolone (Ox) to GH is unclear. Design and Participants: A randomized, placebo-controlled, double-blind, dose-response study was performed in 10

  15. ANDROGENS REGULATE T47D CELLS MOTILITY AND INVASION THROUGH ACTIN CYTOSKELETON REMODELLING

    Directory of Open Access Journals (Sweden)

    Maria Magdalena Montt-Guevara

    2016-09-01

    Full Text Available The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T, dihydrotestosterone (DHT and dehydroepiandrosterone (DHEA may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER, while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.

  16. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment.

    Science.gov (United States)

    Bachmann, Gloria; Bancroft, John; Braunstein, Glenn; Burger, Henry; Davis, Susan; Dennerstein, Lorraine; Goldstein, Irwin; Guay, Andre; Leiblum, Sandra; Lobo, Rogerio; Notelovitz, Morris; Rosen, Raymond; Sarrel, Philip; Sherwin, Barbara; Simon, James; Simpson, Evan; Shifren, Jan; Spark, Richard; Traish, Abdul

    2002-04-01

    To evaluate the evidence for and against androgen insufficiency as a cause of sexual and other health-related problems in women and to make recommendations regarding definition, diagnosis, and assessment of androgen deficiency states in women. Evaluation of peer-review literature and consensus conference of international experts. Multinational conference in the United States. Premenopausal and postmenopausal women with androgen deficiency. Evaluation of peer-review literature and development of consensus panel guidelines. The term "female androgen insufficiency" was defined as consisting of a pattern of clinical symptoms in the presence of decreased bioavailable T and normal estrogen status. Currently available assays were found to be lacking in sensitivity and reliability at the lower ranges, and the need for an equilibrium dialysis measure was strongly emphasized. Causes of androgen insufficiency in women were classified as ovarian, adrenal, hypothalamic-pituitary, drug-related, and idiopathic. A simplified management algorithm and clinical guidelines were proposed to assist clinicians in diagnosis and assessment. Androgen replacement is currently available in several forms, although none has been approved for treatment of sexual dysfunction or other common symptoms of female androgen insufficiency. Potential risks associated with treatment were identified, and the need for informed consent and careful monitoring was noted. Finally, the panel identified key goals and priorities for future research. A new definition of androgen insufficiency in women has been proposed along with consensus-based guidelines for clinical assessment and diagnosis. A simplified management algorithm for women with low androgen in the presence of clinical symptoms and normal estrogen status has also been proposed.

  17. Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

    Science.gov (United States)

    Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

    2017-12-01

    Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life?

    NARCIS (Netherlands)

    Gunning, M. N.; Fauser, B. C.J.M.

    2017-01-01

    To date, the world’s leading cause of death amongst women is cardiovascular disease. Polycystic ovary syndrome (PCOS) is associated with an unfavorable cardiometabolic profile in early life. Apart from dyslipidemia, obesity and onset of type 2 diabetes mellitus, androgens are thought to influence

  19. Androgen deficiency in the aging male and chronic prostatitis: clinical and diagnostic comparative analysis

    Directory of Open Access Journals (Sweden)

    Spirin Р.V.

    2013-03-01

    Full Text Available The research goal is to study probability, period of development and characteristics of a clinical course of chronic prostatitis against the background of androgen deficiency in the aging male. Materials and methods: The Aging Male Symptoms (AMS rating scale has been applied for androgen deficiency evaluation and the International Prostate Symptom Score (IPSS — for chronic prostatitis evaluation. 57 men with chronic prostatitis in combination with androgen deficiency in the aging male have been examined. Results: It has been concluded that the development of chronic prostatitis against the background of androgen deficiency in the aging male occurs in a shorter time period and about 1.5 times more frequently compared to androgen deficiency in the aging male at the background of chronic prostatitis. The analysis of time periods between the onset of chronic prostatitis symptoms against the background of androgen deficiency in the aging male and androgen deficiency in the aging male symptoms against the background of chronic prostatitis showed that androgen deficiency in the aging male symptoms have been revealed 1-2 years earlier than the onset of chronic prostatitis. The development of androgen deficiency in the aging male against the background of chronic prostatitis has showed a backward tendency. Signs of chronic prostatitis have been more frequently occurred in a period of four-five years earlier the androgen deficiency in the aging male development. Conclusion: The risk of development of chronic prostatitis against the background of androgen deficiency in the aging male during the next two years is actually four times higher in comparison with the development of androgen deficiency in the aging male against the background of chronic prostatitis. According to the International Prostate Symptom Score (IPSS, patients with chronic prostatitis in combination with androgen deficiency in the aging male showed higher degree of severity than

  20. Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome.

    Science.gov (United States)

    Lambrinoudaki, Irene

    2011-01-01

    Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders, affecting 5-10% of the female population of reproductive age. "Classic" PCOS is characterized by clinical or biochemical hyperandrogenism and oligo-ovulation. According to the 2003 Rotterdam criteria, two additional phenotypes are recognized: (1) the ovulatory patient with androgen excess and polycystic ovarian morphology and (2) the anovulatory patient with polycystic ovarian morphology without androgen excess. PCOS is associated with an adverse cardiometabolic profile, consisting of increased total or central adiposity, increased blood pressure, a pro-atherogenic lipid profile, increased inflammatory markers, insulin resistance and abnormal glucose metabolism. Furthermore, the incidence of overt or gestational diabetes mellitus, as well as of preeclampsia is significantly higher in PCOS patients. Among the various PCOS phenotypes, those with evidence of androgen excess have the highest burden of cardiovascular risk. Studies evaluating the incidence of cardiovascular disease in postmenopausal women with PCOS are extremely sparse. The available data so far indicate that coronary heart disease, as well as cerebrovascular disease is more common in postmenopausal PCOS patients. Persisting high androgen levels through the menopause, obesity and maturity onset diabetes mellitus are proposed as the main mechanisms accounting for the increased risk. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Androgen responsiveness of the new human endometrial cancer cell line MFE-296.

    Science.gov (United States)

    Hackenberg, R; Beck, S; Filmer, A; Hushmand Nia, A; Kunzmann, R; Koch, M; Slater, E P; Schulz, K D

    1994-04-01

    MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a moderately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were observed. DNA analyses confirmed the genetic identity of the cell line and the patient from whom the cell line was derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT was antagonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 binding sites per cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as demonstrated by transfection experiments with a reporter-gene construct, containing an androgen-responsive element. In MFE-296 cells the content of the androgen receptor was up-regulated by its own ligand.

  2. Blood androgen levels in male baboons throughout the year

    International Nuclear Information System (INIS)

    Taranov, A.G.; Goncharov, N.P.

    1986-01-01

    This paper describes a study of possible dependence of the androgen level in male baboons on the time of year. Plasma was obtained by centrifugation of the blood at 3000 rpm and the following androgens were determined by radioimmunoassay, using chromatographic separation of the steroids on columns with celite: testosterone, 5s-dihydrotestosterone, and dehydroepiandrosterone. Plasma steriod concentrations were calculated and the results were subjected to statistical analysis by Students test. Seasonal change in the concentration of steroids in the animals' blood plasma were discovered. The results of androgen assay throughout the year and determination of their mean annual concentrations are shown

  3. Clinical features and endocrine profile of Laron syndrome in Indian children

    OpenAIRE

    Supriya R Phanse-Gupte; Vaman V Khadilkar; Anuradha V Khadilkar

    2014-01-01

    Introduction: Patients with growth hormone (GH) insensitivity (also known as Laron syndome) have been reported from the Mediterranean region and Southern Eucador, with few case reports from India. We present here the clinical and endocrine profile of 9 children with Laron syndrome from India. Material and Methods: Nine children diagnosed with Laron syndrome based on clinical features of GH deficiency and biochemical profile suggestive of GH resistance were studied over a period of 5 years fro...

  4. Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Yukihiro Nishikawa

    Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

  5. Concept and viability of androgen annihilation for advanced prostate cancer.

    Science.gov (United States)

    Mohler, James L

    2014-09-01

    There remains no standard of care for patients with a rising prostate-specific antigen level after radical prostatectomy or radiotherapy but who have no radiographic metastases, even though this is the second largest group of patients with prostate cancer (CaP) in the United States. Androgen deprivation therapy (ADT) may cure some men with advanced CaP based on single-institution series and a randomized clinical trial of immediate versus delayed ADT for men found to have pelvic lymph node metastasis at the time of radical prostatectomy. ADT may be more effective when initiated for minimal disease burden, which can be detected using PSA after radical prostatectomy or radiotherapy, and if more complete disruption of the androgen axis using newer agents decreases the chance that androgen-sensitive cells survive to adapt to a low-androgen environment. Androgens may be "annihilated" simultaneously using a luteinizing hormone-releasing hormone antagonist or agonist to inhibit testicular production of testosterone, a P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α-reductase (SRD5A) inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer antiandrogen to compete better with DHT for the androgen receptor ligand-binding domain. Early initiation of androgen annihilation for induction as part of planned intermittent ADT should be safe, may reduce tumor burden below a threshold that allows eradication by the immune system, and may cure many men who have failed definitive local therapy. © 2014 American Cancer Society.

  6. Ekspresi Gen CYP19 Aromatase, Estrogen, Androgen pada penderita Periodontitis Agresif

    Directory of Open Access Journals (Sweden)

    Dahlia Herawati

    2016-11-01

    Full Text Available Kepadatan tulang tubuh ditentukan oleh gen CYP19 aromatase, hormon estrogen dan androgen. Pada periodontitis agresif terjadi perkembangan cepat kerusakan tulang alveolar, dan kerusakan tulang alveoler tersebut tidak diimbangioleh regenerasi tulang. Tujuan penelitian ini adalah menunjukkan ekspresi gen CYP19 aromatase, estrogen, androgen pada penderita periodontitis agresif agar dapat untuk menjadi pertimbangan pada saat melakukan perawatan periodontal. Metode penelitian, pemeriksaan ekspresi gen aromatse CYP19 berasal dari spesimen tulang alveolar menggunakan imunohistokimia, pengukuran hormon estrogen dan androgen dari serum menggunakan Vidas: Elfa. Hasil penelitian ekspresi gene CYP19 aromatase pada periodontitis agresif menunjukkan gambaran lebih rendah densitasnya dibandingkan pada nonperiodontitis. Estrogen dan androgen pad aperiodontitis agresif ada kecenderungan lebih rendah dibandingkan pada nonperiodontitis. Kesimpulan regenerasi tulang alveoler pad a periodontitis agresif terhambat karena sedikitnya gen CYP19 aromatase dan hormon estrogen dan androgen yang berperan pada pembentukan tulang alveoler kurang memadai.

  7. ARA24/Ran enhances the androgen-dependent NH2- and COOH-terminal interaction of the androgen receptor

    International Nuclear Information System (INIS)

    Harada, Naoki; Ohmori, Yuji; Yamaji, Ryoichi; Higashimura, Yasuki; Okamoto, Kazuki; Isohashi, Fumihide; Nakano, Yoshihisa; Inui, Hiroshi

    2008-01-01

    The androgen receptor (AR) acts as an androgen-dependent transcription factor controlling the development of prostate tissue. Upon binding to androgen, AR undergoes a dynamic structural change leading to interaction between the NH 2 - and COOH-terminal regions of AR (N-C interaction). ARA24/Ran, which is a small GTPase, functions as an AR coactivator. Here, we report that ARA24/Ran enhances the N-C interaction of AR. The constitutively GTP- or GDP-bound form of ARA24/Ran repressed the AR N-C interaction. ARA24/Ran did not enhance the transcriptional activities of AR mutants that disrupt the N-C interaction. ARA24/Ran formed an endogenous protein complex with nuclear AR, but not cytoplasmic AR. Unlike SRC-1 with the positive activity for AR N-C interaction, ARA24/Ran did not enhance the transcriptional activity of the COOH-terminal domain-deleted AR mutant that is constitutively localized in the nucleus. These data demonstrate that ARA24/Ran increases AR transactivation by enhancing the AR N-C interaction in the nucleus

  8. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2017-10-01

    resistant prostate cancer ; docetaxel; cabazitaxel; chemotherapy; androgen receptor splice variants; microtubule; ligand-binding domain; microtubule... receptor splice variants (AR-Vs) are associated with resistance to taxane chemotherapy in castration- resistant prostate cancer (CRPC). However, this...androgen receptor inhibitors in prostate cancer . Nat Rev Cancer . 2015;15:701–11.

  9. Nutritional support and dietary interventions for women with polycystic ovary syndrome

    OpenAIRE

    Papavasiliou,Kleopatra; Papakonstantinou,Emilia

    2017-01-01

    Kleopatra Papavasiliou, Emilia Papakonstantinou Unit of Human Nutrition, Department of Food Science and Human Nutrition, Agricultural University of Athens, Athens, Greece Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, which leads to reproductive, metabolic and hormonal abnormalities. Hyperinsulinemia, insulin resistance, androgen excess, ovulatory dysfunction, polycystic ovaries, gonadotropin abnormalities, obesity, adipose tissu...

  10. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

    Science.gov (United States)

    Hildebrandt, Tom; Heywood, Ashley; Wesley, Daniel; Schulz, Kurt

    2018-01-01

    Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  11. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

    Directory of Open Access Journals (Sweden)

    Tom Hildebrandt

    2018-03-01

    Full Text Available Synthetic androgens (i. e., anabolic-androgenic steroids are the primary component to the majority of problematic appearance and performance enhancing drug (APED use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc. via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  12. ANABOLIC ANDROGENIC STEROIDS AND ADVERSE EVENTS OF THEIR APPLICATION

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2011-08-01

    Full Text Available Anabolic androgenic steroids are synthetic compounds originating from testosterone. Their main effects are the control of development and expression of male secondary sexual characteristics, which are known as androgenic effects, and encourage muscle growth or anabolic effects. Anabolic androgenic steroids are most commonly used illegal substances. Besides these physiological effects, which are achieved using therapeutic doses of these preparations, higher doses than recommended, especially over the longer term, may be associated with the emergence of numerous adverse events. Adverse events may be registered in almost all organs and organ systems, but usually include changes in the reproductive system, skin, liver and cardiovascular system.

  13. Causes of amenorrhea in Korea: Experience of a single large center

    Science.gov (United States)

    Kwon, Su-Kyoung; Lee, Kyung-Hee; Kim, Sung-Hoon; Kim, Chung-Hoon; Kang, Byung-Moon

    2014-01-01

    Objective To investigate the causes of amenorrhea in Korean women. Methods Medical records from 1,212 women with amenorrhea who visited the Department of Obstetrics and Gynecology, Asan Medical Center, between January 1989 and December 2011 were retrospectively reviewed. Amenorrhea was categorized as either primary or secondary. Results Primary amenorrhea was identified in 132 of the patients (10.9%) and secondary amenorrhea in 1,080 (89.1%). The most frequent causes of primary amenorrhea were gonadal dysgenesis (28.0%, 37/132); Mayer-Rokitansky-Küster-Hauser syndrome (20.0%, 27/132); and constitutional delay and androgen insensitivity syndrome (8.3%, 11/132; 8.3%, 11/132, respectively). Secondary amenorrhea was due to polycystic ovary syndrome (48.4%, 523/1,080); premature ovarian insufficiency (14.0%, 151/1,080); and nutrition-related hypogonadotropic hypogonadism (8.3%, 90/1,080). Conclusion In this retrospective study, gonadal dysgenesis was the most common cause of primary amenorrhea and polycystic ovary syndrome was the most common cause of secondary amenorrhea in Korean women. PMID:24693495

  14. Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Morooka, Nobukatsu, E-mail: amorooka@gunma-u.ac.jp [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Ueguri, Kei [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Yee, Karen Kar Lye [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Human Resources Cultivation Center, Gunma University, 1-5-1 Tenjin-cho, Kiryushi, Gunma, 376-8515 (Japan); Yanase, Toshihiko [Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, 814-0180 (Japan); Sato, Takashi [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan)

    2016-09-02

    Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

  15. Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

    International Nuclear Information System (INIS)

    Morooka, Nobukatsu; Ueguri, Kei; Yee, Karen Kar Lye; Yanase, Toshihiko; Sato, Takashi

    2016-01-01

    Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

  16. Non-neural androgen receptors affect sexual differentiation of brain and behaviour.

    Science.gov (United States)

    Monks, D A; Swift-Gallant, A

    2018-02-01

    Although gonadal testosterone is the principal endocrine factor that promotes masculine traits in mammals, the development of a male phenotype requires local production of both androgenic and oestrogenic signals within target tissues. Much of our knowledge concerning androgenic components of testosterone signalling in sexual differentiation comes from studies of androgen receptor (Ar) loss of function mutants. Here, we review these studies of loss of Ar function and of AR overexpression either globally or selectively in the nervous system of mice. Global and neural mutations affect socio-sexual behaviour and the neuroanatomy of these mice in a sexually differentiated manner. Some masculine traits are affected by both global and neural mutation, indicative of neural mediation, whereas other masculine traits are affected only by global mutation, indicative of an obligatory non-neural androgen target. These results support a model in which multiple sites of androgen action coordinate to produce masculine phenotypes. Furthermore, AR overexpression does not always have a phenotype opposite to that of loss of Ar function mutants, indicative of a nonlinear relationship between androgen dose and masculine phenotype in some cases. Potential mechanisms of Ar gene function in non-neural targets in producing masculine phenotypes are discussed. © 2017 British Society for Neuroendocrinology.

  17. Super-Penetrant Androgen Receptor: Overcoming Enzalutamide Sensitivity in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2016-07-01

    Prostate Cancer Research Symposium- Prostate Cancer Epigenetic Reprogramming of the Androgen Receptor in Castration Resistant Prostate Cancer , May19... cancer cells rely critically on the androgen receptor (AR) for initiation, growth and progression to castration resistant prostate cancer (CRPC...Androgen receptor, castration resistant prostate cancer , Enzalutamide , kinases. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER

  18. ANDROGEN REPLACEMENT THERAPY IN POSTMENOPAUSE

    Directory of Open Access Journals (Sweden)

    Helena Meden Vrtovec

    2008-12-01

    Scientific studies and clinical experiences have not provided until now the answers to thequestion: »Whom to treat, when, why and for how long should androgens be used for HRTin postmenopausal women?«

  19. Nutritional Effect on Androgen-Response Gene Expression and Prostate Tumor Growth

    National Research Council Canada - National Science Library

    Wang, Zhou

    2001-01-01

    .... The dietary influence on ventral prostate weight does not seem to involve androgen action axis because dietary components did not influence the expression of several androgen-response genes, serum testosterone...

  20. Effect of Cuscuta reflexa Roxb on androgen-induced alopecia.

    Science.gov (United States)

    Pandit, Shweta; Chauhan, Nagendra Singh; Dixit, V K

    2008-09-01

    Alopecia is a psychologically distressing condition. Androgenetic alopecia, which affects millions of men and women, is an androgen-driven disorder. Here, Cuscuta reflexa Roxb is evaluated for hair growth activity in androgen-induced alopecia. Petroleum ether extract of C. reflexa was studied for its hair growth-promoting activity. Alopecia was induced in albino mice by testosterone administration for 20 days. Its inhibition by simultaneous administration of extract was evaluated using follicular density, anagen/telogen ratio, and microscopic observation of skin sections. To investigate the mechanism of observed activity, in vitro experiments were performed to study the effect of extract and its major component on activity of 5alpha-reductase enzyme. Petroleum ether extract of C. reflexa exhibited promising hair growth-promoting activity as reflected from follicular density, anagen/telogen ratio, and skin sections. Inhibition of 5alpha-reductase activity by extract and isolate suggest that the extract reversed androgen-induced alopecia by inhibiting conversion of testosterone to dihydrotestosterone. The petroleum ether extract of C. reflexa and its isolate is useful in treatment of androgen-induced alopecia by inhibiting the enzyme 5alpha-reductase.

  1. Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.

    Science.gov (United States)

    Faydaci, Gökhan; Bilal, Eryildirim; Necmettin, Penpegül; Fatih, Tarhan; Asuman, Orçun; Uğur, Kuyumcuoğlu

    2008-12-01

    We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classification was based on Norwood's classification and we categorised baldness as vertex and frontal baldness. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

  2. [Laron syndrome: Presentation, treatment and prognosis].

    Science.gov (United States)

    Latrech, Hanane; Polak, Michel

    2016-01-01

    Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men...... 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do...... not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial...

  4. Characterizations of Factors Affecting Androgen Receptor Transcriptional Regulation in Prostate Cancer

    National Research Council Canada - National Science Library

    Garabedian, Michael

    2003-01-01

    .... Expression of ART-27 in LNCaP cells, an androgen-dependent prostate cancer cell line, reduces androgen-mediated cellular proliferation, suggesting that ART-27 plays a role in suppressing cell growth...

  5. Androgen and androgen metabolite levels in serum and urine of East African chimpanzees (Pan troglodytes schweinfurthii): comparison of EIA and LC-MS analyses.

    Science.gov (United States)

    Preis, Anna; Mugisha, Lawrence; Hauser, Barbara; Weltring, Anja; Deschner, Tobias

    2011-12-01

    The primary male androgen testosterone (T) is often used as an endocrinological marker to investigate androgen-behaviour interactions in males. In chimpanzees and bonobos, studies investigating the relationship between T levels and dominance rank or aggressive behaviour have revealed contradictory results. The immunoassays used in these studies were originally developed for the measurement of steroids in serum. Their application to non-invasively collected samples, however, can lead to methodological problems due to cross-reacting metabolites, which might occur in urine or faeces but not in blood. The overall aim of this study, therefore, is to clarify whether a T enzyme immunoassay (EIA) is an applicable method to monitor testicular function in adult male chimpanzees. To estimate the impact of cross-reacting androgens on the used T EIA, we compared the results of an EIA measurement with a set of androgen metabolite levels measured by LC-MS. In urine from male chimpanzees, cross-reactivities appear to exist mainly with T and its exclusive metabolites, 5α-dihydrotestosterone (5α-DHT) and 5α-androstanediol (androstanediol). Both urinary and serum T levels of male chimpanzees were significantly higher than female T levels when measured with the T EIA, indicating a reliable measurement of testicular androgens and their exclusive metabolites with the used EIA. In urine from female chimpanzees, the comparison between LC-MS and T EIA results indicated a higher impact of cross-reactions with adrenal androgen metabolites. Therefore, the investigation of urinary T levels in female chimpanzees with a T EIA seems to be problematic. Overall our results show that a T EIA can be a reliable method to monitor testicular function in male chimpanzee urine and that LC-MS is a valuable tool for the validation of immunoassays. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Polarization Insensitive One-to-Six WDM Multicasting in a Silicon Nanowire

    DEFF Research Database (Denmark)

    Pu, Minhao; Hu, Hao; Peucheret, Christophe

    2012-01-01

    We present polarization insensitive one-to-six WDM multicasting based on nondegenerate four-wave mixing in a silicon nanowire with angled-pump scheme. Bit-error rate measurements are performed and error-free operation is achieved.......We present polarization insensitive one-to-six WDM multicasting based on nondegenerate four-wave mixing in a silicon nanowire with angled-pump scheme. Bit-error rate measurements are performed and error-free operation is achieved....

  7. Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with Turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Stijnen, T.; Zandwijken, G.R.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

    2011-01-01

    BACKGROUND: The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). METHODS: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose

  8. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

    Science.gov (United States)

    Rosenfield, Robert L; Ehrmann, David A

    2016-10-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity

  9. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited

    Science.gov (United States)

    Ehrmann, David A.

    2016-01-01

    Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989–1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired

  10. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics

    DEFF Research Database (Denmark)

    Jensen, Anne Skakkebæk; Bojesen, A; Kristensen, M. K.

    2014-01-01

    Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra......-inactivation, CAG repeat length and parent-of-origin have no impact on the neuropsychological phenotype in KS (http://www.clinicaltrials.gov (Clinical trial NCT00999310))....

  11. ASSESSMENT OF IN VITRO ANDROGENIC ACTIVITY IN KRAFT MILL EFFLUENT

    Science.gov (United States)

    Detection of In Vitro Androgenic Activity in Feedlot Effluent. Lambright, CS 1 , Guillette, LJ, Jr.2, Gray, LE, Jr.1 , 1USEPA, NHEERL, RTP, NC, 2 University of Florida, Dept. of Zoology, Gainesville FLRecent studies have shown the presence of androgenic activity in water...

  12. Estrogens and Androgens in Skeletal Physiology and Pathophysiology

    OpenAIRE

    Almeida, Maria; Laurent, Michaël R.; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A.; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C.

    2016-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably t...

  13. Androgenic anabolic steroid use among male adolescents in Falkenberg.

    Science.gov (United States)

    Nilsson, S

    1995-01-01

    Recent reports show that androgenic anabolic steroids are used by many teenagers, not as a deliberate attempt to give them strength, better athletic performance, etc., but to improve their looks. The so-called macho cult among young boys tempts them into using androgenic anabolic steroids to give them bigger muscles and a more powerful appearance. This study was undertaken to investigate the prevalence of androgenic anabolic steroid use among teenagers in a small town and to create a platform for future work with the aim of decreasing the misuse of these drugs. In Falkenberg, a town in the county of Halland in the west of Sweden, the pupils at two high schools were investigated by means of an anonymous multiple-choice questionnaire. A total of 1383 students (688 males and 695 females) aged 14-19 years participated in the study, giving a participation rate of 96%. The number of answers completed was 99%. The use of androgenic anabolic steroids is a reality among male teenagers in Falkenberg, with 5.8% of them using the drugs. Among 15- to 16-year-old boys misuse of these drugs is as high as 10%, and of these 50% (5.0% of total) also inject ampoules of the drugs. This prevalence is alarming since the adverse effects of androgenic anabolic steroids are more serious in teenagers. Serious action must be taken to inform teenagers of the consequences of misusing drugs.

  14. Evidence That Androgens Modulate Human Thymic T Cell Output

    Science.gov (United States)

    Olsen, Nancy J.; Kovacs, William J.

    2010-01-01

    Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

  15. Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

    Science.gov (United States)

    Segal, Scott; Narayanan, Ramesh; Dalton, James T

    2006-04-01

    Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

  16. NDIA 2018 IM and EM Technology Symposium: Innovative Insensitive Munition Solutions for Enhanced Warfighter Effectiveness

    Science.gov (United States)

    2018-04-26

    2018 IM & EM TECHNOLOGY SYMPOSIUM INNOVATIVE INSENSITIVE MUNITION SOLUTIONS FOR ENHANCED WARFIGHTER EFFECTIVENESS April 23 – 26, 2018 Doubletree by...IM & EM TECHNOLOGY SYMPOSIUM On behalf of the Insensitive Munitions and Energetic Materials Committee and our MSIAC partner, I would like to...welcome you to the 2018 Insensitive Munitions and Energetic Materials Technology Symposium. This international gathering of the top chemists, system

  17. Androgen levels in women with various forms of ovarian dysfunction : Associations with cardiometabolic features

    NARCIS (Netherlands)

    Daan, N. M P; Jaspers, L.; Koster, M. P H; Broekmans, F. J M; De Rijke, Y. B.; Franco, O. H.; Laven, J. S E; Kavousi, M.; Fauser, B. C J M

    2015-01-01

    STUDY QUESTION Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were

  18. Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.

    Science.gov (United States)

    Jahromi, Marziyeh Salehi; Tehrani, Fahimeh Ramezani; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

    2016-11-15

    It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; PPCOS. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice.

    Science.gov (United States)

    Chisamore, Michael J; Gentile, Michael A; Dillon, Gregory Michael; Baran, Matthew; Gambone, Carlo; Riley, Sean; Schmidt, Azriel; Flores, Osvaldo; Wilkinson, Hilary; Alves, Stephen E

    2016-10-01

    The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT

  20. Androgen receptor CAG repeat polymorphism and epigenetic influence among the south Indian women with Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Shilpi Dasgupta

    Full Text Available The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13 and controls (18.73±0.12. The obese PCOS women were significantly more frequent in the 20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p=0.001. Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p=0.33. CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women.

  1. Steroid Androgen Exposure during Development Has No Effect on Reproductive Physiology of Biomphalaria glabrata.

    Directory of Open Access Journals (Sweden)

    Satwant Kaur

    Full Text Available Gastropod mollusks have been proposed as alternative models for male reproductive toxicity testing, due to similarities in their reproductive anatomy compared to mammals, together with evidence that endocrine disrupting chemicals can cause effects in some mollusks analogous to those seen in mammals. To test this hypothesis, we used the freshwater pulmonate snail, Biomphalaria glabrata, for which various genetic tools and a draft genome have recently become available, to investigate the effects of two steroid androgens on the development of mollusk secondary sexual organs. Here we present the results of exposures to two potent androgens, the vertebrate steroid; 5α-dihydrotestosterone (DHT and the pharmaceutical anabolic steroid; 17α-methyltestosterone (MT, under continuous flow-through conditions throughout embryonic development and up to sexual maturity. Secondary sexual gland morphology, histopathology and differential gene expression analysis were used to determine whether steroid androgens stimulated or inhibited organ development. No significant differences between tissues from control and exposed snails were identified, suggesting that these androgens elicited no biologically detectable response normally associated with exposure to androgens in vertebrate model systems. Identifying no effect of androgens in this mollusk is significant, not only in the context of the suitability of mollusks as alternative model organisms for testing vertebrate androgen receptor agonists but also, if applicable to other similar mollusks, in terms of the likely impacts of androgens and anti-androgenic pollutants present in the aquatic environment.

  2. Polarization insensitive wavelength conversion in a dispersion-engineered silicon waveguide

    DEFF Research Database (Denmark)

    Pu, Minhao; Hu, Hao; Peucheret, Christophe

    2012-01-01

    We experimentally demonstrate polarization-insensitive all optical wavelength conversion of a 10-Gb/s DPSK data signal based on four-wave mixing in a silicon waveguide with an angled-pump scheme. Dispersion engineering is applied to the silicon waveguide to obtain similar four-wave mixing convers...... conversion performances for both the TE and TM modes. Bit-error rate measurements are performed and error-free operation is achieved. We also demonstrate polarization-insensitive wavelength conversion with a large separation between the idler and signal using a dual-pump configuration....

  3. Peripheral conversion and uptake of androgens in a XXY-man with Klinefelter's syndrome

    International Nuclear Information System (INIS)

    Sulcova, J.; Jirasek, J.E.; Neuwirth, J.; Raboch, J.; Starka, L.

    1978-01-01

    The conversion of 3 H-testosterone and the uptake of 3 H-testosterone and 3 H-5α-dihydrotestosterone were investigated in pubic skin and pubic hair follicles of a XXY-man with inadequate pubic hair. The uptake of both androgens was demonstrated in the skin as well as in the hair follicles. Similarly the activity of steroid 5α-reductase was present in both tissues. The total conversion of 3 H-testosterone was 2-3 times higher in the patient than in control persons. In the XXY-man the major metabolites were 5α- and 5β-androstanediols, whereas in the normal men 5α-dihydrotestosterone and 4-androstenedione were mainly formed from testosterone. An explanation of the inadequate growth of pubic hair in our patient seems to be related to a conversion of testosterone - at its low plasma level - to its relatively inactive metabolites. (author)

  4. O2-insensitive photosynthesis in C3 plants: its occurrence and a possible explanation

    International Nuclear Information System (INIS)

    Sharkey, T.D.

    1985-01-01

    Leaves of C 3 plants which exhibit a normal O 2 inhibition of CO 2 fixation at less than saturating light intensity were found to exhibit O 2 -insensitive photosynthesis at high light. This behavior was observed in Phaseolus vulgaris L., Xanthium strumarium L., and Scrophularia desertorum (Shaw.) Munz. O 2 -insensitive photosynthesis has been reported in nine other C 3 species and usually occurred when the intercellular CO 2 pressure was about double the normal pressure. A lack of O 2 inhibition of photosynthesis was always accompanied by a failure of increased CO 2 pressure to stimulate photosynthesis to the expected degree. O 2 -insensitive photosynthesis also occurred after plants had been water stressed. Under such conditions, however, photosynthesis became O 2 and CO 2 insensitive at physiological CO 2 pressures. Postillumination CO 2 exchange kinetics showed that O 2 and CO 2 insensitivity was not the result of elimination of photorespiration. It is proposed that O 2 and CO 2 insensitivity occurs when the concentration of phosphate in the chloroplast stroma cannot be both high enough to allow photophosphorylation and low enough to allow starch and sucrose synthesis at the rates required by the rest of the photosynthetic component processes. Under these conditions, the energy diverted to photorespiration does not adversely affect the potential for CO 2 assimilation

  5. Muscle Dysfunction in Androgen Deprivation: Role of Ryanodine Receptor

    Science.gov (United States)

    2016-11-01

    reversible pharmacological treatment is a key therapeutic goal in prostate cancer patients. This life prolonging treatment is accompanied by the adverse... reversible pharmacological treatment, is a key therapeutic goal of androgen deprivation therapies (ADT) used in patients with androgen-dependent...gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. Aug 2000;85(8):2839

  6. The Limitations to Delay-Insensitivity in Asynchronous Circuits

    National Research Council Canada - National Science Library

    Martin, Alain J

    1990-01-01

    ... produced are delay-insensitive (DI). A digital circuit is DI when its correct operation is independent of the delays in operators and in the wires connecting the operators, except that the delays are finite and positive...

  7. The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

    International Nuclear Information System (INIS)

    Chuu, Chih-pin; Chen, Rou-Yu; Hiipakka, Richard A.; Kokontis, John M.; Warner, Karen V.; Xiang, Jialing; Liao, Shutsung

    2007-01-01

    T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells

  8. The overlap between Binge Eating Behaviors and Polycystic Ovarian Syndrome: An etiological integrative model.

    Science.gov (United States)

    Paganini, Chiara; Peterson, Gregory; Stavropoulos, Vasilis; Krug, Isabel

    2017-12-04

    Studies indicate that Polycystic Ovarian Syndrome (PCOS) features (e.g. insulin instability, food cravings, overproduction of androgens and menstrual irregularities) associate with increased appetite, impaired impulse control and feelings of body dissatisfaction. Counter intuitively, binge eating behaviors have been shown to reinforce PCOS symptomatology, precipitating concurrently body dissatisfaction, weight gain, insulin instability and overproduction of androgens. The present systematic literature review aspires to investigate the relationship between binge eating, in the broader context of eating disorder behaviors, and Polycystic Ovarian Syndrome (PCOS), taking into account shared characteristics between EDs (Eating Disorders) and PCOS. To address this aim the PRISMA guidelines are adopted. A total of 21 studies, which investigated the presence of binge eating in PCOS population and the presence of PCOS in EDs population, were synthesized. Findings suggested that an increased prevalence of binge eating has been reported in women with Polycystic Ovarian Syndrome (PCOS); and that women suffering from BN (Bulimia Nervosa) and BED (Binge Eating Disorder) are more likely to display polycystic ovaries. Further research on their shared liability is required in order to inform more efficient prevention and treatment initiatives for populations presenting with comorbid features. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications.

    Science.gov (United States)

    Lucas-Herald, Angela K; Alves-Lopes, Rheure; Montezano, Augusto C; Ahmed, S Faisal; Touyz, Rhian M

    2017-07-01

    The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca 2+ mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  10. Chinese Herbal Medicine for the Optimal Management of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Ong, Madeleine; Peng, Jie; Jin, Xingliang; Qu, Xianqin

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.

  11. New Temperature-Insensitive Electronically-Tunable Grounded Capacitor Simulator

    OpenAIRE

    Abuelma'atti, Muhammad Taher; Khan, Muhammad Haroon

    1996-01-01

    A new circuit for simulating a grounded capacitor is presented. The circuit uses one operationalamplifier (OA), three operational-transconductance amplifiers (OTAs), and one capacitor. The realized capacitor is temperature-insensitive and electronically tunable. Experimental results are included.

  12. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring.

    Science.gov (United States)

    Abbott, David H; Bruns, Cristin R; Barnett, Deborah K; Dunaif, Andrea; Goodfriend, Theodore L; Dumesic, Daniel A; Tarantal, Alice F

    2010-11-01

    Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155-175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in

  13. Broadband temperature-insensitivity of dispersion-engineered waveguides and resonators

    Science.gov (United States)

    Xu, Lijuan; He, Liuqing; Guo, Yuhao; Li, Guifang; Zhang, Lin

    2018-02-01

    Photonic circuits suffer from thermal drift of device performance, which is a key obstacle to the development of commercial optoelectronic products. Temperature-insensitive integrated waveguides and resonators have been demonstrated by using materials with a negative TOC at a single wavelength, which are not suitable for WDM devices and wideband nonlinear devices. Here, we propose a waveguide structure with temperature-insensitivity over a bandwidth of 780 nm (1280 to 2060 nm) with an ultra-small effective TOC within +/-1×10-6/K. Uniquely, the waveguide has small anomalous dispersion (from 66 to 329 ps/nm/km) over the same band and is suitable for frequency comb generation without being affected by intra-cavity thermal dynamics.

  14. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kim, Joonyoung; Jones, Lynne A.; Mercer, Nicole M.; Engelbach, John A.; Sharp, Terry L.; Welch, Michael J. E-mail: welchm@mir.wustl.edu

    2002-11-01

    PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, {sup 18}F-FDG and {sup 11}C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 {mu}g dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, n = 18), Group B (DES, no-DHT, n = 18) and Group C (DES, DHT, n = 18). In each group, 10 animals received {sup 18}F-FDG, whereas the remaining eight animals were administered {sup 11}C-acetate. Rats were sacrificed at 120 min post-injection of {sup 18}F-FDG or 30 min post-injection of {sup 11}C-acetate. Pretreatment of the mouse model using DHT (200 {mu}g of DHT in 0.1 mL of sunflower seed oil) or DES (200 {mu}g of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in {sup 18}F-FDG study, while there was no significant difference in {sup 11}C-acetate uptake. These results indicate that changes in serum testosterone levels influence {sup 18}F-FDG uptake in the prostate gland, which is closely tied to glucose

  15. Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters ZIP14 and ZNT1 in Obesity and Polycystic Ovary Syndrome

    DEFF Research Database (Denmark)

    Maxel, Trine; Svendsen, Pernille Fog; Smidt, Kamille

    2017-01-01

    Polycystic ovary syndrome (PCOS) is associated with infertility, increased androgen levels, and insulin resistance. In adipose tissue, zinc facilitates insulin signaling. Circulating zinc levels are altered in obesity, diabetes, and PCOS; and zinc supplementation can ameliorate metabolic...

  16. A comparative study on androgen metabolism in three invertebrate species.

    Science.gov (United States)

    Janer, G; LeBlanc, G A; Porte, C

    2005-09-15

    A comparative approach was taken in this study to evaluate androgen (androstenedione and testosterone) metabolism in three invertebrate species: the gastropod Marisa cornuarietis, the amphipod Hyalella azteca, and the echinoderm Paracentrotus lividus. The existence of 17beta/3beta-hydroxysteroid dehydrogenase (HSD) and 5alpha-reductase catalyzed reactions was demonstrated in all three species. Androstenedione was primarily converted to 5alpha-androstanedione in M. cornuarietis, while it was primarily metabolized to testosterone in P. lividus and H. azteca. In addition, and consistent with vertebrate findings, tissue specific pathways and sexual dimorphism in androgen metabolism were observed. Namely, testosterone was metabolized to dihydrotestosterone in P. lividus gonads (via 5alpha-reductase), and metabolized to 4-androstene-3beta,17beta-diol in the digestive tube (via 3beta-hydroxysteroid dehydrogenase). Furthermore, the synthesis of 17beta-reduced metabolites of androstenedione (testosterone and dihydrotestosterone) was 3- to 4-fold higher in males of M. cornuarietis than in females. Organotin compounds, which have been shown to interfere with some aspects of androgen metabolism, had no major effect on testosterone metabolism in any of the three species. Fenarimol enhanced 5alpha-reductase-mediated catalysis in gonads of P. lividus. Overall, results demonstrate the ubiquity of some androgen biotransformation processes in invertebrates and reveals interphyla differences in androgen metabolic pathways, and different sensitivity of these pathways to some xenobiotics.

  17. Enzalutamide inhibits androgen receptor-positive bladder cancer cell growth.

    Science.gov (United States)

    Kawahara, Takashi; Ide, Hiroki; Kashiwagi, Eiji; El-Shishtawy, Kareem A; Li, Yi; Reis, Leonardo O; Zheng, Yichun; Miyamoto, Hiroshi

    2016-10-01

    Emerging preclinical evidence suggests that androgen-mediated androgen receptor (AR) signals promote bladder cancer progression. However, little is known about the efficacy of an AR signaling inhibitor, enzalutamide, in the growth of bladder cancer cells. In this study, we compared the effects of enzalutamide and 2 other classic antiandrogens, flutamide and bicalutamide, on androgen-induced bladder cancer cell proliferation, migration, and invasion as well as tumor growth in vivo. Thiazolyl blue cell viability assay, flow cytometry, scratch wound-healing assay, transwell invasion assay, real-time polymerase chain reaction, and reporter gene assay were performed in AR-positive (e.g., UMUC3, TCCSUP, and 647V-AR) and AR-negative (e.g., UMUC3-AR-short hairpin RNA [shRNA], TCCSUP-AR-shRNA, 647V) bladder cancer lines treated with dihydrotestosterone and each AR antagonist. We also used a mouse xenograft model for bladder cancer. Dihydrotestosterone increased bladder cancer cell proliferation, migration, and invasion indicating that endogenous or exogenous AR was functional. Enzalutamide, hydroxyflutamide, and bicalutamide showed similar inhibitory effects, without significant agonist activity, on androgen-mediated cell viability/apoptosis, cell migration, and cell invasion in AR-positive lines. No significant effects of dihydrotestosterone as well as AR antagonists on the growth of AR-negative cells were seen. Correspondingly, in UMUC3 cells, these AR antagonists down-regulated androgen-induced expression of AR, matrix metalloproteinase-2, and interleukin-6. Androgen-enhanced AR-mediated transcriptional activity was also blocked by each AR antagonist exhibiting insignificant agonist activity. In UMUC3 xenograft-bearing mice, oral gavage treatment with each antiandrogen retarded tumor growth, and only enzalutamide demonstrated a statistically significant suppression compared with mock treatment. Our current data support recent observations indicating the involvement of

  18. Androgen Ablation Augments Prostate Cancer Vaccine Immunogenicity Only When Applied After Immunization

    Science.gov (United States)

    Koh, Yi T.; Gray, Andrew; Higgins, Sean A.; Hubby, Bolyn; Kast, W. Martin

    2009-01-01

    Background Androgen ablation (AA) causes apoptosis of normal and neoplastic prostate cells. It is a standard treatment for advanced prostate cancer. Androgen ablation-mediated immunological effects include bone marrow hyperplasia, thymic regeneration, T and B cell lymphopoeisis and restoration of age-related peripheral T cell dysfunction. Androgens also regulate the transcription of several cytokines. Dendritic cells (DC) are the most potent antigen presenting cells that can activate antigen-specific naïve T cells. Despite myriad clinical trials involving DC-based prostate cancer immunotherapies, the effects of AA on DC function remain largely uncharacterized. Therefore, we investigated the effects of AA on DC and whether it could improve the efficacy of prostate cancer immunotherapy. Methods Cytokine expression changes due to AA were quantified by multiplex ELISA. Flow cytometry was used to assess AA-mediated effects on DC maturation and expression of costimulatory markers. Mixed leukocyte reactions and cell-mediated lysis assays elucidated the role of androgens in DC function. The effect of AA on the efficacy of vaccination against a prostate tumor-associated antigen was tested using Elispot assays. Results Androgen ablation increased dendritic cell maturation and costimulatory marker expression, but had no effect on DC costimulatory function. However, DC isolated from castrated mice increased the expression of key cytokines by antigen-experienced T cells while decreasing their expression in naïve cells. Finally, androgen ablation improved immune responses to vaccination only when applied after immunization. Conclusion Androgen ablation causes differential effects of DC on primary and secondary T cell responses, thus augmenting vaccine immunogenicity only when applied after immunization. PMID:19143030

  19. Prevalent flucocorticoid and androgen activity in US water sources

    Science.gov (United States)

    Stavreva, Diana A.; George, Anuja A.; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C.; Schiltz, R. Louis; Blazer, Vicki; Iwanowiczl, Luke R.; Hager, Gordon L.

    2012-01-01

    Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

  20. Prevalent glucocorticoid and androgen activity in US water sources.

    Science.gov (United States)

    Stavreva, Diana A; George, Anuja A; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C; Schiltz, R Louis; Blazer, Vicki S; Iwanowicz, Luke R; Hager, Gordon L

    2012-01-01

    Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

  1. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  2. Network analysis of an in vitro model of androgen-resistance in prostate cancer

    International Nuclear Information System (INIS)

    Detchokul, Sujitra; Elangovan, Aparna; Crampin, Edmund J.; Davis, Melissa J.; Frauman, Albert G.

    2015-01-01

    The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer). We established an androgen-independent subline from LNCaP cells by prolonged exposure to androgen-deprivation. We examined phenotypic profiles and performed RNA-sequencing. The reads generated were compared to human clinical samples and were analysed using differential expression, pathway analysis and protein-protein interaction networks. After 24 weeks of androgen-deprivation, LNCaP cells had increased proliferative and invasive behaviour compared to parental LNCaP, and its growth was no longer responsive to androgen. We identified key genes and pathways that overlap between our cell line and clinical RNA sequencing datasets and analysed the overlapping protein-protein interaction network that shared the same pattern of behaviour in both datasets. Mechanisms bypassing androgen receptor signalling pathways are significantly enriched. Several steroid hormone receptors are differentially expressed in both datasets. In particular, the progesterone receptor is significantly differentially expressed and is part of the interaction network disrupted in both datasets. Other signalling pathways commonly altered in prostate cancer, MAPK and PI3K-Akt pathways, are significantly enriched in both datasets. The overlap between the human and cell-line differential expression profiles and protein networks was statistically significant showing that the cell-line model reproduces molecular patterns observed in

  3. Congenital insensitivity to pain: Case report of a rare entity

    Directory of Open Access Journals (Sweden)

    Swati Dahiya

    2018-01-01

    Full Text Available Hereditary sensory and autonomic neuropathies (HSANs are a group of disorders characterized by insensitivity to noxious stimuli and autonomic dysfunction, associated with pathological abnormalities of the peripheral nerves. Five types of HSAN have been reported in literature, out of which Type V known as congenital insensitivity to pain (CIP is a rare autosomal recessive condition. Self-mutilation is an invariable feature of this disorder, involving the teeth and orofacial structures. This case report describes a case of a 6-year-old girl with CIP brought by her parents for prostheses to replace her self-extracted primary teeth.

  4. Aging and Immunopathology in Primary Sjögren's Syndrome.

    Science.gov (United States)

    Bouma, Hjalmar R; Bootsma, Hendrika; van Nimwegen, Jolien F; Haacke, Erlin A; Spijkervet, Fred K; Vissink, Arjan; Kroese, Frans G M

    2015-01-01

    Sicca complaints (sensation of dry mouth and/or eyes) are present in about a quarter of the individuals above the age of 65 years old and are mainly due to medication. However, physiological changes that occur during aging might also lead to a diminished glandular function. These age-related changes are, at least in part, to be the consequence of decreased androgen levels. In addition to these physiological effects that occur during normal aging, sicca complaints can also be caused by Sjögren's syndrome (SS): a systemic auto-inflammatory disorder mainly affecting exocrine glands. Genetic factors, lowered levels of gonadal hormones and (viral) infections appear to contribute to the etiology of the syndrome. The incidence of SS is higher among aged individuals, which might be due to earlier diagnosis, as the onset of SS in an individual with age-related exocrine gland dysfunction lowers the threshold for sicca complaints. On the other hand, physiological aging might be considered as a risk factor for development of SS, resulting in a faster development of the syndrome. Differentiating physiological sicca complaints from SS in the elderly can be challenging, since apparently healthy individuals might present with auto-antibodies and lymphocytic infiltrates in salivary glands might be present as well. The drop in the level of androgens and estrogens upon aging, immunosenescence and pro-inflammatory features of the aging immune system may all contribute to the etiology of pSS in the elderly. In this review, we describe the physiological effects of aging and the influence of SS on exocrine gland morphology and function.

  5. Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life?

    Science.gov (United States)

    Gunning, M N; Fauser, B C J M

    2017-06-01

    To date, the world's leading cause of death amongst women is cardiovascular disease. Polycystic ovary syndrome (PCOS) is associated with an unfavorable cardiometabolic profile in early life. Apart from dyslipidemia, obesity and onset of type 2 diabetes mellitus, androgens are thought to influence cardiovascular health. The question rises whether women with PCOS are truly at risk for cardiovascular disease in later life. In this review paper, we aim to reflect on this assumed relation based on studies in different stages of life in women with PCOS. Cardiovascular risk factors (type 2 diabetes mellitus, obesity and metabolic syndrome), surrogate outcomes (flow-mediated dilation, carotid intima-media thickness and coronary artery calcium) and clinical long-term outcomes (cardiovascular disease and mortality) will be summarized. Data on cardiovascular disease and mortality in peri- and postmenopausal women with PCOS appear to be controversial. Whether androgens have a protective or unfavorable influence on the manifestation of cardiovascular disease remains uncertain. The need for large, prospective, well-phenotyped cohort studies of women with PCOS is high. Only then will we be able to answer this research question.

  6. Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

    Science.gov (United States)

    Ramalingam, Sundhar; Eisenberg, Adva; Foo, Wen Chi; Freedman, Jennifer; Armstrong, Andrew J; Moss, Larry G; Harrison, Michael R

    2016-12-01

    Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome. © 2016 The Japanese Urological Association.

  7. Changes in microfilament and focal adhesion distribution with loss of androgen responsiveness in cultured mammary tumor cells

    DEFF Research Database (Denmark)

    Couchman, J R; Yates, J; King, R J

    1981-01-01

    of the cells to grow in suspension culture. All these parameters were documented for androgen-responsive and -unresponsive cells grown in culture, as well as the transition of androgen-responsive to -unresponsive cells when deprived of androgen. The androgen-unresponsive cells had extensive and prominent...... microfilament bundles together with focal adhesions on the lower cell surface and also showed strict anchorage dependence for growth. In contrast, microfilament bundles and focal adhesions were absent from androgen-responsive cells, which furthermore had the ability to grow in suspension culture. Differences......, characteristics of both cell types were visible in the cell populations. However, at the stage where all androgen-responsive characteristics were lost, the cells were no longer androgen sensitive. The loss of androgen responsiveness in Shionogi 115 mouse mammary tumor cells is correlated with changes at the cell...

  8. Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems.

    Directory of Open Access Journals (Sweden)

    Ryan Tasseff

    Full Text Available Androgen ablation therapy is currently the primary treatment for metastatic prostate cancer. Unfortunately, in nearly all cases, androgen ablation fails to permanently arrest cancer progression. As androgens like testosterone are withdrawn, prostate cancer cells lose their androgen sensitivity and begin to proliferate without hormone growth factors. In this study, we constructed and analyzed a mathematical model of the integration between hormone growth factor signaling, androgen receptor activation, and the expression of cyclin D and Prostate-Specific Antigen in human LNCaP prostate adenocarcinoma cells. The objective of the study was to investigate which signaling systems were important in the loss of androgen dependence. The model was formulated as a set of ordinary differential equations which described 212 species and 384 interactions, including both the mRNA and protein levels for key species. An ensemble approach was chosen to constrain model parameters and to estimate the impact of parametric uncertainty on model predictions. Model parameters were identified using 14 steady-state and dynamic LNCaP data sets taken from literature sources. Alterations in the rate of Prostatic Acid Phosphatase expression was sufficient to capture varying levels of androgen dependence. Analysis of the model provided insight into the importance of network components as a function of androgen dependence. The importance of androgen receptor availability and the MAPK/Akt signaling axes was independent of androgen status. Interestingly, androgen receptor availability was important even in androgen-independent LNCaP cells. Translation became progressively more important in androgen-independent LNCaP cells. Further analysis suggested a positive synergy between the MAPK and Akt signaling axes and the translation of key proliferative markers like cyclin D in androgen-independent cells. Taken together, the results support the targeting of both the Akt and MAPK

  9. Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Rosenberg JE

    2012-01-01

    Full Text Available Yasser Rehman1, Jonathan E Rosenberg21Division of Hospital Medicine, UMass Memorial Healthcare, Worcester, MA, USA; 2Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC, which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17. This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.Keywords: CRPC, abiraterone, CYP17, inhibitors, androgens, castration resistant prostate cancer

  10. Etiology of homosexuality.

    Science.gov (United States)

    Headings, V E

    1980-08-01

    The range of expression of homosexuality and its association with certain cultural, environmental, and genetic factors are most consistent with the concept of a multifactorial trait. Additionally, genetic heterogeneity in this phenotype (alternative mutants corresponding to a single phenotype) is highly probable. In certain nonhuman and presumably in human species the normal sexual development of the hypothalamus is guided by an appropriate exposure to androgen at a critical early stage, and this in turn presumably contributes to sociopsychologic sex development. Particularly instructive in this regard have been the monogenic experiments of nature in man--XY females with insensitivity to androgens, congenital adrenal hyperplasia, and male pseudohermaphrodites (5-alpha-reductase deficiency). Additionally, in the human, sociopsychologic sex also appears to be molded by sex assigned at birth and sex of rearing. Several of the intersexuality syndromes and psychoses are accompanied by increased homosexuality, but a majority of homosexuals are not in these categories. A limited number of family studies, including twins, tentatively suggests a heritable risk, at least in some families.

  11. Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

    2018-04-25

    Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing

  12. Identification of a novel androgen receptor agonist (or “androgen mimic”) of environmental concern: spironolactone

    Science.gov (United States)

    Spironolactone is a pharmaceutical that acts as an androgen receptor (AR) antagonist in humans to treat certain conditions such as hirsutism, various dermatologic afflictions, and female pattern hair loss. The drug is also used to treat hypertension as a diuretic. With this commo...

  13. The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Jafari-Sfidvajani, S; Ahangari, R; Hozoori, M; Mozaffari-Khosravi, H; Fallahzadeh, H; Nadjarzadeh, A

    2018-05-01

    Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this studywas to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women. In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or (2) weight-loss intervention + placebo. At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups. After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75-20) ng/ml to 42.69 (34-53.25) ng/ml in vitamin D group compared to placebo group (p weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups. In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved. IRCT2016062710826N19.

  14. Establishment of a novel immortalized human prostatic epithelial cell line stably expressing androgen receptor and its application for the functional screening of androgen receptor modulators

    International Nuclear Information System (INIS)

    Yu, Shan; Wang, Ming-Wei; Yao, Xiaoqiang; Chan, F.L.

    2009-01-01

    In this study, we developed a human prostatic epithelial cell line BPH-1-AR stably expressing AR by lentiviral transduction. Characterization by immunoblot and RT-PCR showed that AR was stably expressed in all representative BPH-1-AR clones. Androgen treatment induced a secretory differentiation phenotype in BPH-1-AR cells but suppressed their cell proliferation. Treatments with AR agonists induced transactivation of a transfected PSA-gene promoter reporter in BPH-1-AR cells, whereas this transactivation was suppressed by an AR antagonist flutamide, indicating that the transduced AR in BPH-1-AR cells was functional. Finally, we utilized BPH-1-AR cells to evaluate the androgenic activities and growth effects of five newly developed non-steroidal compounds. Results showed that these compounds showed androgenic activities and growth-inhibitory effects on BPH-1-AR cells. Our results showed that BPH-1-AR cell line would be a valuable in vitro model for the study of androgen-regulated processes in prostatic epithelial cells and identification of compounds with AR-modulating activities.

  15. Epidemiology, diagnosis, and management of polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Sirmans SM

    2013-12-01

    Full Text Available Susan M Sirmans, Kristen A PateDepartment of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USAAbstract: Polycystic ovary syndrome (PCOS is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.Keywords: polycystic ovary syndrome

  16. Delinquency, androgens, and the family: a test of evolutionary neuroandrogenic theory.

    Science.gov (United States)

    Ellis, Lee; Das, Shyamal

    2013-08-01

    There is little doubt that family factors can influence involvement in delinquency, although the full nature and extent of their influences remain unclear. In recent decades, testosterone has been increasingly implicated as a contributor to adolescent offending. The present study sought to determine whether two important types of familial factors--parental socioeconomic status and amicable parent-child relationships--are interacting with testosterone (and possibly other androgens) to affect delinquency. A large sample of North American college students self-reported their involvement in eight categories of delinquency along with self-ratings of various androgen-promoted traits (e.g., muscularity and low-deep voice), parental social status, and the quality of the relationships they had with parents. In both sexes, parent-child relationships and androgens were significantly associated with delinquency but parental social status was not. Factor analysis revealed that the authors' measures of all four categories of variables exhibited strong loadings onto their respective factors. Androgens and amicable parent-child relationships were associated with delinquency but parental social status was not. About one third of the influence of parent-child relationships on delinquency appeared to be attributable to androgens. Findings are discussed from the perspective of the evolutionary neuroandrogenic theory of delinquent and criminal behavior.

  17. Targeting the androgen receptor in triple-negative breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Mina A

    2017-09-01

    Full Text Available Alain Mina,1 Rachel Yoder,2 Priyanka Sharma1 1Division of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, 2University of Kansas Cancer Center, Kansas City, KS, USA Abstract: Triple-negative breast cancer (TNBC is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition. Keywords: triple-negative breast cancer, androgen signaling, targeted therapy, biomarkers, prognosis 

  18. PCOS Forum: research in polycystic ovary syndrome today and tomorrow.

    Science.gov (United States)

    Pasquali, Renato; Stener-Victorin, Elisabet; Yildiz, Bulent O; Duleba, Antoni J; Hoeger, Kathleen; Mason, Helen; Homburg, Roy; Hickey, Theresa; Franks, Steve; Tapanainen, Juha S; Balen, Adam; Abbott, David H; Diamanti-Kandarakis, Evanthia; Legro, Richard S

    2011-04-01

    To summarize promising areas of investigation into polycystic ovary syndrome (PCOS) and to stimulate further research in this area. Summary of a conference held by international researchers in the field of polycystic ovary syndrome. Potential areas of further research activity include the analysis of predisposing conditions that increase the risk of PCOS, particularly genetic background and environmental factors, such as endocrine disruptors and lifestyle. The concept that androgen excess may contribute to insulin resistance needs to be re-examined from a developmental perspective, since animal studies have supported the hypothesis that early exposure to modest androgen excess is associated with insulin resistance. Defining alterations of steroidogenesis in PCOS should quantify ovarian, adrenal and extraglandular contribution, as well as clearly define blood reference levels by some universal standard. Intraovarian regulation of follicle development and mechanisms of follicle arrest should be further elucidated. Finally, PCOS status is expected to have long-term consequences in women, specifically the development of type 2 diabetes, cardiovascular diseases and hormone dependent cancers. Identifying susceptible individuals through genomic and proteomic approaches would help to individualize therapy and prevention. There are several intriguing areas for future research in PCOS. A potential limitation of our review is that we focused selectively on areas we viewed as the most controversial. © 2011 Blackwell Publishing Ltd.

  19. The effect of oxandrolone on body proportions and body composition in growth hormone-treated girls with Turner syndrome.

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Zandwijken, G.R.; Ridder, M.A. de; Stijnen, T.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

    2010-01-01

    OBJECTIVE: Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone

  20. Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

    Science.gov (United States)

    Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

    2014-02-07

    Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

  1. Androgen effects on skeletal muscle: implications for the development and management of frailty

    Directory of Open Access Journals (Sweden)

    Matthew DL O'Connell

    2014-04-01

    Full Text Available Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.

  2. Stromal Androgen Receptor in Prostate Cancer Development and Progression

    Science.gov (United States)

    Leach, Damien A.; Buchanan, Grant

    2017-01-01

    Prostate cancer development and progression is the result of complex interactions between epithelia cells and fibroblasts/myofibroblasts, in a series of dynamic process amenable to regulation by hormones. Whilst androgen action through the androgen receptor (AR) is a well-established component of prostate cancer biology, it has been becoming increasingly apparent that changes in AR signalling in the surrounding stroma can dramatically influence tumour cell behavior. This is reflected in the consistent finding of a strong association between stromal AR expression and patient outcomes. In this review, we explore the relationship between AR signalling in fibroblasts/myofibroblasts and prostate cancer cells in the primary site, and detail the known functions, actions, and mechanisms of fibroblast AR signaling. We conclude with an evidence-based summary of how androgen action in stroma dramatically influences disease progression. PMID:28117763

  3. TREATMENT OF METABOLIC ALTERATIONS IN POLYCYSTIC OVARY SYNDROME.

    Science.gov (United States)

    Păvăleanu, Ioana; Gafiţanu, D; Popovici, Diana; Duceac, Letiţia Doina; Păvăleanu, Maricica

    2016-01-01

    Polycystic ovary syndrome is a common endocrinopathy characterized by oligo ovulation or anovulation, signs of androgen excess and multiple small ovarian cysts. It includes various metabolic abnormalities: insulin resistance, hyperinsulinemia, impaired glucose tolerance, visceral obesity, inflammation and endothelial dysfunction, hypertension and dyslipidemia. All these metabolic abnormalities have long-term implications. Treatment should be individualized and must not address a single sign or symptom. Studies are still needed to determine the benefits and the associated risks of the medication now available to practitioners.

  4. Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

    Science.gov (United States)

    Izumi, Kouji; Li, Lei; Chang, Chawnshang

    2014-01-01

    Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

  5. Effects of triazole fungicides on androgenic disruption and CYP3A4 enzyme activity.

    Science.gov (United States)

    Lv, Xuan; Pan, Liumeng; Wang, Jiaying; Lu, Liping; Yan, Weilin; Zhu, Yanye; Xu, Yiwen; Guo, Ming; Zhuang, Shulin

    2017-03-01

    Triazole fungicides are widely used as broad-spectrum fungicides, non-steroidal antiestrogens and for various industrial applications. Their residues have been frequently detected in multiple environmental and human matrices. The increasingly reported toxicity incidents have led triazole fungicides as emerging contaminants of environmental and public health concern. However, whether triazole fungicides behave as endocrine disruptors by directly mimicking environmental androgens/antiandrogens or exerting potential androgenic disruption indirectly through the inhibition of cytochrome P450 (CYP450) enzyme activity is yet an unresolved question. We herein evaluated five commonly used triazole fungicides including bitertanol, hexaconazole, penconazole, tebuconazole and uniconazole for the androgenic and anti-androgenic activity using two-hybrid recombinant human androgen receptor (AR) yeast bioassay and comparatively evaluated their effects on enzymatic activity of CYP3A4 by P450-Glo™ CYP3A4 bioassay. All five fungicides showed moderate anti-androgenic activity toward human AR with the IC 50 ranging from 9.34 μM to 79.85 μM. The anti-androgenic activity remained no significant change after the metabolism mediated by human liver microsomes. These fungicides significantly inhibited the activity of CYP3A4 at the environmental relevant concentrations and the potency ranks as tebuconazole > uniconazole > hexaconazole > penconazole > bitertanol with the corresponding IC 50 of 0.81 μM, 0.93 μM, 1.27 μM, 2.22 μM, and 2.74 μM, respectively. We found that their anti-androgenic activity and the inhibition potency toward CYP3A4 inhibition was significantly correlated (R 2 between 0.83 and 0.97, p pesticides and structurally similar chemicals should fully consider potential androgenic disrupting effects and the influences on the activity of CYP450s. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  7. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Science.gov (United States)

    Dowling, Abigail R; Nedorezov, Laura B; Qiu, Xiaoliang; Marino, Joseph S; Hill, Jennifer W

    2013-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  8. CYP19 gene expression in subcutaneous adipose tissue is associated with blood pressure in women with polycystic ovary syndrome.

    Science.gov (United States)

    Lecke, Sheila B; Morsch, Débora M; Spritzer, Poli M

    2011-11-01

    In polycystic ovary syndrome (PCOS), hypertension has been linked to androgen excess and insulin resistance. Aromatase, an enzyme encoded by the CYP19 gene, affects androgen metabolism and estrogen synthesis, influencing the androgen to estrogen balance. We characterized CYP19 gene expression in subcutaneous adipose tissue of women with PCOS and normal controls and evaluated the association between subcutaneous fat CYP19 mRNA, circulating hormone levels, and blood pressure. This case-control study was carried out with 31 PCOS patients and 27 BMI-matched normotensive non-hirsute women with regular cycles. Participants underwent anthropometric measurements, collection of blood samples, and adipose tissue biopsy (28 PCOS and 19 controls). Hypertension was defined as systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg. PCOS patients were divided into normotensive and hypertensive. Main outcome measures were serum estrogen and androgen levels, estrogen-to-androgen ratio, and CYP19 gene expression in subcutaneous fat. Subcutaneous CYP19 mRNA was higher in hypertensive PCOS than in control and normotensive PCOS women (p = 0.014). Estrogen-to-androgen ratio was lower in hypertensive PCOS than controls (p androgen ratio ≤ 0.06 (median for the three groups) was observed in 91% of hypertensive PCOS women, vs. 37% and 61% in the control and normotensive PCOS groups (p = 0.011). CYP19 gene expression in subcutaneous fat of PCOS patient correlated positively with systolic (p = 0.006) and diastolic blood pressure (p = 0.009). Androgen excess and hyperinsulinemia may play a role in the molecular mechanisms that activate aromatase mRNA transcription in abdominal fat tissue. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Zebrafish (Danio rerio) androgen receptor: sequence homology and up-regulation by the fungicide vinclozolin.

    Science.gov (United States)

    Smolinsky, Amanda N; Doughman, Jennifer M; Kratzke, Liên-Thành C; Lassiter, Christopher S

    2010-03-01

    Steroid hormones regulate gene expression in organisms by binding to receptor proteins. These hormones include the androgens, which signal through androgen receptors (ARs). Endocrine disrupters (EDCs) are chemicals in the environment that adversely affect organisms by binding to nuclear receptors, including ARs. Vinclozolin, a fungicide used on fruit and vegetable crops, is a known anti-androgen, a type of EDC that blocks signals from testosterone and its derivatives. In order to better understand the effects of EDCs, further research on androgen receptors and other hormone signaling pathways is necessary. In this study, we demonstrate the evolutionary conservation between the genomic structure of the human and zebrafish ar genes and find that ar mRNA expression increases in zebrafish embryos exposed to vinclozolin, which may be evolutionarily conserved as well. At 48 and 72 h post-fertilization, vinclozolin-treated embryos express ar mRNA 8-fold higher than the control level. These findings suggest that zebrafish embryos attempt to compensate for the presence of an anti-androgen by increasing the number of androgen receptors available.

  10. Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2013-06-01

    Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

  11. LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ali Zhang

    2015-10-01

    Full Text Available Understanding the mechanisms of androgen receptor (AR activation in the milieu of low androgen is critical to effective treatment of castration-resistant prostate cancer (CRPC. Here, we report HOTAIR as an androgen-repressed lncRNA, and, as such, it is markedly upregulated following androgen deprivation therapies and in CRPC. We further demonstrate a distinct mode of lncRNA-mediated gene regulation, wherein HOTAIR binds to the AR protein to block its interaction with the E3 ubiquitin ligase MDM2, thereby preventing AR ubiquitination and protein degradation. Consequently, HOTAIR expression is sufficient to induce androgen-independent AR activation and drive the AR-mediated transcriptional program in the absence of androgen. Functionally, HOTAIR overexpression increases, whereas HOTAIR knockdown decreases, prostate cancer cell growth and invasion. Taken together, our results provide compelling evidence of lncRNAs as drivers of androgen-independent AR activity and CRPC progression, and they support the potential of lncRNAs as therapeutic targets.

  12. Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

    Science.gov (United States)

    Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

    2014-09-05

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Leuprolide acetate-stimulated androgen response during female puberty.

    Science.gov (United States)

    Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

    2015-08-01

    A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with

  14. Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

    Science.gov (United States)

    Samino, Sara; Vinaixa, Maria; Díaz, Marta; Beltran, Antoni; Rodríguez, Miguel A; Mallol, Roger; Heras, Mercedes; Cabre, Anna; Garcia, Lorena; Canela, Nuria; de Zegher, Francis; Correig, Xavier; Ibáñez, Lourdes; Yanes, Oscar

    2015-06-23

    Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide.

  15. Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Antoine D Rolland

    Full Text Available The capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion.

  16. Prevalence of Polycystic Ovary Syndrome Phenotypes Using Updated Criteria for Polycystic Ovarian Morphology: An Assessment of Over 100 Consecutive Women Self-reporting Features of Polycystic Ovary Syndrome

    OpenAIRE

    Clark, Nina M.; Podolski, Amanda J.; Brooks, Eric D.; Chizen, Donna R.; Pierson, Roger A.; Lehotay, Denis C.; Lujan, Marla E.

    2014-01-01

    The prevalence of polycystic ovary syndrome (PCOS) and its distinct clinical phenotypes were assessed using 3 sets of international diagnostic criteria in women self-reporting concerns over outward features of PCOS. Revised ultrasonographic criteria for polycystic ovaries (PCO) based on modern ultrasound technology were used. Of the participants, 53%, 62%, and 70% were diagnosed with PCOS using National Institutes of Health, Androgen Excess and PCOS Society, and Rotterdam criteria, respective...

  17. Effects of fenoterol on the skeletal system depend on the androgen level.

    Science.gov (United States)

    Śliwiński, Leszek; Cegieła, Urszula; Pytlik, Maria; Folwarczna, Joanna; Janas, Aleksandra; Zbrojkiewicz, Małgorzata

    2017-04-01

    The role of sympathetic nervous system in the osseous tissue remodeling is not clear enough. The effects of fenoterol, a selective β 2 -adrenomimetic drug, on the skeletal system of normal and androgen deficient (orchidectomized) rats were studied in vivo. Osteoclastogenesis and mRNA expression in osteoblasts were investigated in vitro in mouse cell cultures. Fenoterol administered to animals with physiological androgen level unfavorably affected the skeletal system, damaging the bone microarchitecture. Androgen deficiency induced osteoporotic changes, and fenoterol protected the osseous tissue from consequences of androgen deficiency. The results of in vitro studies correlated with the in vivo observations. A significantly increased number of osteoclasts in bone marrow cell cultures to which testosterone and fenoterol were added simultaneously was demonstrated. In cultures without the addition of testosterone, fenoterol significantly inhibited osteoclastogenesis in comparison with control cultures. The results indicate the favorable action of fenoterol in conditions of testosterone deficiency, and its destructive influence upon the skeleton in the presence of androgens. The results confirm the key role of sympathetic nervous system in the regulation of bone remodeling. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  18. Long-term effects of oxandrolone treatment in childhood on neurocognition, wellbeing and social-emotional functioning in young adults with Turner syndrome

    NARCIS (Netherlands)

    Freriks, K.; Verhaak, C.M.; Sas, T.C.J.; Menke, L.A.; Wit, J.M.; Otten, B.J.; Muinck Keizer-Schrama, S.M.P.F. de; Smeets, D.F.C.M.; Netea-Maier, R.T.; Hermus, A.R.M.M.; Kessels, R.P.C.; Timmers, H.J.L.M.

    2015-01-01

    Turner syndrome (TS) is the result of (partial) absence of one X-chromosome. Besides short stature, gonadal dysgenesis and other physical aspects, TS women have typical psychological features. Since psychological effects of androgen exposure in childhood probably are long-lasting, we explored

  19. Environmental effects on hormonal regulation of testicular descent

    DEFF Research Database (Denmark)

    Toppari, J; Virtanen, H E; Skakkebaek, N E

    2006-01-01

    cause some cases of undescended testis. Similarly, androgen insensitivity or androgen deficiency can cause cryptorchidism. Estrogens have been shown to down regulate INSL3 and thereby cause maldescent. Thus, a reduced androgen-estrogen ratio may disturb testicular descent. Environmental effects changing......Regulation of testicular descent is hormonally regulated, but the reasons for maldescent remain unknown in most cases. The main regulatory hormones are Leydig cell-derived testosterone and insulin-like factor 3 (INSL3). Luteinizing hormone (LH) stimulates the secretion of these hormones...... hypothesize that an exposure to a mixture of chemicals with anti-androgenic or estrogenic properties (either their own activity or their effect on androgen-estrogen ratio) may be involved in cryptorchidism....

  20. Androgenic signaling systems and their role in behavioral evolution.

    Science.gov (United States)

    Fuxjager, Matthew J; Schuppe, Eric R

    2018-06-05

    Sex steroids mediate the organization and activation of masculine reproductive phenotypes in diverse vertebrate taxa. However, the effects of sex steroid action in this context vary tremendously, in that steroid action influences reproductive physiology and behavior in markedly different ways (even among closely related species). This leads to the idea that the mechanisms underlying sex steroid action similarly differ across vertebrates in a manner that supports diversification of important sexual traits. Here, we highlight the Evolutionary Potential Hypothesis as a framework for understanding how androgen-dependent reproductive behavior evolves. This idea posits that the cellular mechanisms underlying androgenic action can independently evolve within a given target tissue to adjust the hormone's functional effects. The result is a seemingly endless number of permutations in androgenic signaling pathways that can be mapped onto the incredible diversity of reproductive phenotypes. One reason this hypothesis is important is because it shifts current thinking about the evolution of steroid-dependent traits away from an emphasis on circulating steroid levels and toward a focus on molecular mechanisms of hormone action. To this end, we also provide new empirical data suggesting that certain cellular modulators of androgen action-namely, the co-factors that dynamically adjust transcritpional effects of steroid action either up or down-are also substrates on which evolution can act. We then close the review with a detailed look at a case study in the golden-collared manakin (Manacus vitellinus). Work in this tropical bird shows how androgenic signaling systems are modified in specific parts of the skeletal muscle system to enhance motor performance necessary to produce acrobatic courtship displays. Altogether, this paper seeks to develop a platform to better understand how steroid action influences the evolution of complex animal behavior. Copyright © 2018 Elsevier Ltd

  1. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation.

    Science.gov (United States)

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B; He, Yali; Siddam, Anjaiah; Miller, Duane D; Dalton, James T

    2010-08-01

    Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in our laboratories have shown the beneficial effects of selective androgen receptor modulators (SARMs) in the treatment of osteoporosis and muscle wasting in animal models. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-trifluoromethyl-phenyl)-propionamide analogs was synthesized to evaluate the effects of B-ring substitutions on in vitro and in vivo pharmacologic activity, especially female sexual motivation. The androgen receptor (AR) relative binding affinities ranged from 0.1 to 26.5% (relative to dihydrotestosterone) and demonstrated a range of agonist activity at 100 nM. In vivo pharmacologic activity was first assessed by using male rats. Structural modifications to the B-ring significantly affected the selectivity of the SARMs, demonstrating that single-atom substitutions can dramatically and unexpectedly influence activity in androgenic (i.e., prostate) and anabolic (i.e., muscle) tissues. (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro,4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) displayed full agonist activity in androgenic and anabolic tissues; however, the remaining SARMs were more prostate-sparing, selectively maintaining the size of the levator ani muscle in castrated rats. The partner-preference paradigm was used to evaluate the effects of SARMs on female sexual motivation. With the exception of two four-halo substituted analogs, the SARMs increased sexual motivation in ovariectomized rats, with potency and efficacy comparable with testosterone propionate. These results indicate that the AR is important in regulating female libido given the nonaromatizable nature of SARMs and it could be a superior alternative to steroidal testosterone preparations in the treatment of hypoactive sexual desire disorder.

  2. Androgen metabolism in invertebrates and its modulation by xenoandrogens: a comparative study.

    Science.gov (United States)

    Janer, G; Leblanc, G A; Porte, C

    2005-04-01

    Marisa cornuarietis (Mollusc), Hyalella azteca (Crustacean), and Paracentrotus lividus (Echinoderm) demonstrated the ability to metabolize androgens through different pathways catalyzed by 5alpha-reductases (5alpha-R), hydroxysteroid dehydrogenases (HSD), hydroxylases, sulfotransferases (SULT), and fatty-acid acyl-CoA acyltransferases (ATAT). Interspecies differences and tissue-specific distribution of those enzymatic activities were observed. Xenobiotics, such as triphenyltin, tributyltin, and fenarimol, interfered with some of the pathways studied, namely, testosterone sulfation, testosterone esterification, and 5alpha-R activity. The work evidenced different sensitivity of those pathways to androgenic compounds, together with interphyla differences in androgen metabolism.

  3. Prevalence of metabolic syndrome in polycystic ovarian syndrome women in a hospital of Tehran

    Directory of Open Access Journals (Sweden)

    Ashraf Moini

    2012-01-01

    Full Text Available Background: Polycystic ovarian syndrome (PCOS is a condition associated with chronic anovulation, insulin resistance and androgen excess. Women with this syndrome are at increased risk of metabolic syndrome. Objective: The aim of the present study was to determine the prevalence of metabolic syndrome (MBS in women with PCOS referred to Arash Hospital in different ages and body mass index (BMI. Materials and Methods: A cross-sectional study was conducted in Gynecologic Clinic at Arash Hospital affiliated with Tehran University. A total of 282 women with PCOS ages between 15-40 years were included. The prevalence of Metabolic Syndrome and its components in this population were the main outcomes. Height, weight, waist circumference, blood pressure and laboratory tests (FBS, TSH, HDL-C, serum prolactin, triglycerides and total cholesterol were measured in this population. Results: The prevalence of MBS in PCOS women was 22.7% (64 cases. The rate of central obesity, FBS more than 110 mg/dl, triglycerides more than 150 mg/dl, high-density lipoprotein cholesterol levels (HDL-C less than 50 mg/dl, and blood pressure ≥130/85 mmHg in PCOS women was 31% (87, 3.2% (9, 33% (93, 68.8% (194, and 10.6% (30, respectively. The risk of MBS was increased in older and the obese women (BMI ≥30 kg/m2. Conclusion: The present sample showed women with PCOS have a high prevalence of MBS and its individual components, particularly decreased HDL-C.

  4. Critical androgen-sensitive periods of rat penis and clitoris development.

    Science.gov (United States)

    Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

    2010-02-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its

  5. Metabolic Syndrome: Polycystic Ovary Syndrome.

    Science.gov (United States)

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  6. Minoxidil may suppress androgen receptor-related functions.

    Science.gov (United States)

    Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

    2014-04-30

    Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a K(d) value of 2.6 µM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

  7. Polarization-insensitive quantum-dot coupled quantum-well semiconductor optical amplifier

    International Nuclear Information System (INIS)

    Huang Lirong; Yu Yi; Tian Peng; Huang Dexiu

    2009-01-01

    The optical gain of a quantum-dot semiconductor optical amplifier is usually seriously dependent on polarization; we propose a quantum-dot coupled tensile-strained quantum-well structure to obtain polarization insensitivity. The tensile-strained quantum well not only serves as a carrier injection layer of quantum dots but also offers gain to the transverse-magnetic mode. Based on the polarization-dependent coupled carrier rate-equation model, we study carrier competition among quantum well and quantum dots, and study the polarization dependence of the quantum-dot coupled quantum-well semiconductor optical amplifier. We also analyze polarization-dependent photon-mediated carrier distribution among quantum well and quantum dots. It is shown that polarization-insensitive gain can be realized by optimal design

  8. Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals

    DEFF Research Database (Denmark)

    Körner, Wolfgang; Vinggaard, Anne; Terouanne, B.

    2004-01-01

    steroidal androgens, two antiandrogens, an androgenic control, 5alpha-dihydrotestosterone (DHT), and an antiandrogenic control, bicalutamide (ICI 176,334). All laboratories correctly detected the androgenic activity of 4-androsten-3,17-dione and 17alpha-methyl-testosterone. For both compounds...

  9. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    International Nuclear Information System (INIS)

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125 I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125 I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

  10. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaini, Ramesh R. [Department of Biochemistry and Molecular Biology and UNM Cancer and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM (United States); Hu, Chien-An A., E-mail: AHu@salud.unm.edu [Department of Biochemistry and Molecular Biology and UNM Cancer and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. Black-Right-Pointing-Pointer Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. Black-Right-Pointing-Pointer Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. Black-Right-Pointing-Pointer Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showed that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.

  11. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

    International Nuclear Information System (INIS)

    Kaini, Ramesh R.; Hu, Chien-An A.

    2012-01-01

    Highlights: ► Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. ► Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. ► Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. ► Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showed that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.

  12. Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

    Science.gov (United States)

    Dulka, Eden A; Moenter, Suzanne M

    2017-11-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

  13. Effects of combined exposure to anti-androgens on development and sexual dimorphic behaviour in rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    Summary Background: Androgens are key regulators of male sexual differentiation during the in utero and early postnatal development. Exposure to endocrine disrupting chemicals (EDCs) that counteract androgen action at some stage in these periods can permanently demasculinise male foetuses and lead......?  Is sexually dimorphic behaviour in rats affected at lower dose levels of anti-androgens and thereby a more sensitive endpoint than morphological effects on the male external reproductive organs? The thesis is based on the results of in vivo studies where mated female Wistar rats were exposed to anti......-androgens either alone or in mixtures during pregnancy and lactation. The endpoints examined for anti-androgenic effects in the offspring were: Anogenital distance (AGD), nipple retention (NR), and external (morphological) malformations in pups and sexually mature male rats. Furthermore, the effects of the anti...

  14. Is foetal hyperexposure to androgens a cause of PCOS?

    Science.gov (United States)

    Filippou, Panagiota; Homburg, Roy

    2017-07-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence. They are also thought to re-programme the female reproductive axis to induce the features of PCOS in later life: oligo/anovulation, polycystic ovaries, hyperandrogenism and insulin resistance (IR). Support for this developmental theory for the aetiology of PCOS is gathering momentum, following results from first animal studies and now human data, which lend credence to many aspects of this hypothesis. In this review the recent available evidence is presented to support the hypothesis that hyperandrogenic changes in the intra-uterine environment could play a major part in the aetiological basis of PCOS. An extensive PubMED and MEDline database search was conducted. Relevant studies were identified using a combination of search terms: 'polycystic ovary syndrome', 'PCOS', 'aetiology', 'anti-Mullerian hormone', 'AMH', 'pathogenesis', 'kisspeptin', 'hyperandrogenism', 'insulin resistance', 'metabolic factors', 'placenta', 'developmental hypothesis', 'genetic and epigenetic origins'. A total of 82 studies were finally included in this review. There is robust evidence that a hyperandrogenic intra-uterine environment 'programmes' the genes concerned with ovarian steroidogenesis, insulin metabolism, gonadotrophin secretion and ovarian follicle development resulting in the development of PCOS in adult life. Once the evidence supporting this hypothesis has been expanded by additional studies, the door would be open to

  15. Features of Polycystic Ovary Syndrome in adolescence.

    Science.gov (United States)

    Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, G F

    2015-01-01

    To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman's life. To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. PCOS = Polycystic Ovary Syndrome.

  16. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Harold D Love

    2009-12-01

    Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  17. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

    Science.gov (United States)

    Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

    2015-05-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  18. The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-01-01

    Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

  19. Illicit Anabolic-Androgenic Steroid Use

    Science.gov (United States)

    Kanayama, Gen; Hudson, James I.; Pope, Harrison G.

    2009-01-01

    The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body-image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years, but remains little studied. PMID:19769977

  20. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    Science.gov (United States)

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. © 2016 The Author(s).

  1. Polarization Insensitive Wavelength Conversion Based on Four-Wave Mixing in a Silicon Nanowire

    DEFF Research Database (Denmark)

    Pu, Minhao; Hu, Hao; Peucheret, Christophe

    2012-01-01

    We experimentally demonstrate, for the first time, polarization-insensitive wavelength conversion of a 10 Gb/s NRZ-OOK data signal based on four-wave mixing in a silicon nanowire with bit-error rate measurements.......We experimentally demonstrate, for the first time, polarization-insensitive wavelength conversion of a 10 Gb/s NRZ-OOK data signal based on four-wave mixing in a silicon nanowire with bit-error rate measurements....

  2. Epidemiology, diagnosis, and management of polycystic ovary syndrome

    Science.gov (United States)

    Sirmans, Susan M; Pate, Kristen A

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications. PMID:24379699

  3. Epidemiology, diagnosis, and management of polycystic ovary syndrome.

    Science.gov (United States)

    Sirmans, Susan M; Pate, Kristen A

    2013-12-18

    Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

  4. Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Z

    2001-01-01

    The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

  5. Long-term effects of oxandrolone treatment in childhood on neurocognition, quality of life and social-emotional functioning in young adults with Turner syndrome

    NARCIS (Netherlands)

    Freriks, K.; Verhaak, C.M.; Sas, T.C.; Menke, L.A.; Wit, J.M.; Otten, B.J.; Keizer-Schrama, S.M.; Smeets, D.F.C.M.; Netea-Maier, R.T.; Hermus, A.R.M.M.; Kessels, R.P.C.; Timmers, H.J.L.M.

    2015-01-01

    Turner syndrome (TS) is the result of (partial) absence of one X-chromosome. Besides short stature, gonadal dysgenesis and other physical aspects, TS women have typical psychological features. Since psychological effects of androgen exposure in childhood probably are long-lasting, we explored

  6. Load Insensitive, Low Voltage Quadrature Oscillator Using Single Active Element

    Directory of Open Access Journals (Sweden)

    Jitendra Mohan

    2017-01-01

    Full Text Available In this paper, a load insensitive quadrature oscillator using single differential voltage dual-X second generation current conveyor operated at low voltage is proposed. The proposed circuit employs single active element, three grounded resistors and two grounded capacitors. The proposed oscillator offers two load insensitive quadrature current outputs and three quadrature voltage outputs simultaneously. Effects of non-idealities along with the effects of parasitic are further studied. The proposed circuit enjoys the feature of low active and passive sensitivities. Additionally, a resistorless realization of the proposed quadrature oscillator is also explored. Simulation results using PSPICE program on cadence tool using 90 nm Complementary Metal Oxide Semiconductor (CMOS process parameters confirm the validity and practical utility of the proposed circuit.

  7. Expression of androgen receptor target genes in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kesha Rana

    2014-10-01

    Full Text Available We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 Kip2, Igf2 and calcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all but p57 Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  8. Cytogenetic Analysis for Research and Services

    Directory of Open Access Journals (Sweden)

    Sultana MH Faradz

    2017-02-01

    Full Text Available Abstract That the correct chromosome number in man is 46 was first recognized by Tjio and Levan in 1956. Perhaps few Indonesians know that Tjio was an Indonesian scientist studying in Sweden and then living in the US. Cytogenetic analyses are commonly performed to determine both structural and numerical chromosome aberration, whilst changes in chromosomes can lead to birth defects, syndromes, or even cancer.  Several chromosomal aneuploidy syndromes were identified after the establishment of various chromosome banding techniques in late 1960’s.  Specific cell culture media was found to express fragile site in the beginning of 1970’s and since then, inherited Fragile X Mental Retardation syndrome could be diagnosed.  However, some female permutation cases have been often misdiagnosed. Further molecular analysis has resolved this problem by revealing more CGG repeats in the promoter region FMR1 gene, which is related to the expression of fragile site and the severity of the diseases. In Disorder of Sex Development (DSD, early gender assignment and reconstruction surgery has been challenged because of the dilemma of gender identity development in later life. Cytogenetic analysis for the first-line gender assignment is important in newborn with DSD. Proper diagnosis with hormonal and mutation analysis should be elucidated to avoid medical, psychological, and social aspect in adult life. The most frequent genetic cases in our clinical experiences have been Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia. Female Complete Androgen Insensitivity Syndrome (CAIS with main symptom primary amenorrhea without cytogenetic analysis has often been diagnosed as inguinal hernia because of testicle location and size. Diagnosis and treatment of several leukemias and lymphomas, as well as some solid tumors, depend on cytogenetic analyses to demonstrate consistent, specific chromosomal aberrations. Chromosome analysis in hematologic

  9. Contributions of sex, testosterone, and androgen receptor CAG repeat number to virtual Morris water maze performance.

    Science.gov (United States)

    Nowak, Nicole T; Diamond, Michael P; Land, Susan J; Moffat, Scott D

    2014-03-01

    The possibility that androgens contribute to the male advantage typically found on measures of spatial cognition has been investigated using a variety of approaches. To date, evidence to support the notion that androgens affect spatial cognition in healthy young adults is somewhat equivocal. The present study sought to clarify the association between testosterone (T) and spatial performance by extending measurements of androgenicity to include both measures of circulating T as well as an androgen receptor-specific genetic marker. The aims of this study were to assess the contributions of sex, T, and androgen receptor CAG repeat number (CAGr) on virtual Morris water task (vMWT) performance in a group of healthy young men and women. The hypothesis that men would outperform women on vMWT outcomes was supported. Results indicate that CAGr may interact with T to impact navigation performance and suggest that consideration of androgen receptor sensitivity is an important consideration in evaluating hormone-behavior relationships. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.

    Science.gov (United States)

    Boer, Hink; Westerink, Nico-Derk L; Altena, Renske; Nuver, Janine; Dijck-Brouwer, D A Janneke; van Faassen, Martijn; Klont, Frank; Kema, Ido P; Lefrandt, Joop D; Zwart, Nynke; Boezen, H Marike; Smit, Andries J; Meijer, Coby; Gietema, Jourik A

    2016-02-01

    Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors. In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2. The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The Androgen Receptor Gene Mutations Database.

    Science.gov (United States)

    Gottlieb, B; Lehvaslaiho, H; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

    1998-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1; (iii) by adding information on large gene deletions; (iv) by providing a direct link with a completely searchable database (courtesy EMBL-European Bioinformatics Institute). The addition of the exon 1 polymorphisms is discussed in light of their possible relevance as markers for predisposition to prostate or breast cancer. The database is also available on the internet (http://www.mcgill. ca/androgendb/ ), from EMBL-European Bioinformatics Institute (ftp. ebi.ac.uk/pub/databases/androgen ), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca).

  12. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

    Science.gov (United States)

    Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

    2007-04-01

    Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether

  13. The Central Effects of Androgenic-anabolic Steroid Use.

    Science.gov (United States)

    Mędraś, Marek; Brona, Anna; Jóźków, Paweł

    : Millions of men use androgenic-anabolic steroids (AAS) to stimulate muscle growth and improve physical appearance. Although 1 out of 3 people who uses androgenic-anabolic steroids develops a steroid use disorder, the effects of the drugs on the central nervous system and the psyche are still not well understood. Although most addictive substances improve mood immediately after administration, AAS exert less pronounced euphoric effects. Instead, they are primarily taken for the delayed gratification of increased muscle mass. Withdrawal from AAS may lead to a range of somatic and psychiatric symptoms, and, in many cases, comprehensive treatment supervised by an endocrinologist and a psychiatrist is required.

  14. On the proluminal movement of 3H-androgens across the rat epididymal epithelium

    International Nuclear Information System (INIS)

    Turner, T.T.; Jones, C.E.; Roddy, M.S.

    1989-01-01

    3H-Androgens in rat epididymal interstitium have previously been shown to move into the epididymal lumen against a concentration gradient. This is true especially in the caput epididymidis. The present investigation used the technique of in vivo epididymal perifusion and tubule micropuncture to demonstrate that the proluminal movement of 3H-androgens is subject to competitive inhibition (unlabeled testosterone in the perifusion fluid at 10 times and 100 times the concentration of 3H-testosterone significantly reduced proluminal movement of isotope) and is not energy-dependent (1 mM 2,4-dinitrophenol in perifusion fluid did not reduce the proluminal movement of isotope). Additionally, dry-mount autoradiography demonstrated high intraluminal concentrations of isotope relative to interstitial concentrations after caput tubule incubation in 3H-dihydrotestosterone (3H-DHT), and showed that the high intraluminal concentrations of isotope were not dependent on the presence of spermatozoa, i.e. proluminal movement of 3H-androgens was not due to binding to intraluminal spermatozoa. Isolation of caput epididymidal sperm on filters followed by 3H-DHT binding experiments also failed to demonstrate the presence of specific binding of this androgen to spermatozoa. Finally, it was confirmed that electrophoresed epididymal lumen fluid contains a single 3H-DHT binding peak that is at its highest concentration in the caput epididymal fluid. These data are consistent with the conclusion that intraluminal androgen-binding protein is an important factor in transepithelial androgen movement

  15. Delay Insensitive Ternary CMOS Logic for Secure Hardware

    Directory of Open Access Journals (Sweden)

    Ravi S. P. Nair

    2015-09-01

    Full Text Available As digital circuit design continues to evolve due to progress of semiconductor processes well into the sub 100 nm range, clocked architectures face limitations in a number of cases where clockless asynchronous architectures generate less noise and produce less electro-magnetic interference (EMI. This paper develops the Delay-Insensitive Ternary Logic (DITL asynchronous design paradigm that combines design aspects of similar dual-rail asynchronous paradigms and Boolean logic to create a single wire per bit, three voltage signaling and logic scheme. DITL is compared with other delay insensitive paradigms, such as Pre-Charge Half-Buffers (PCHB and NULL Convention Logic (NCL on which it is based. An application of DITL is discussed in designing secure digital circuits resistant to side channel attacks based on measurement of timing, power, and EMI signatures. A Secure DITL Adder circuit is designed at the transistor level, and several variance parameters are measured to validate the efficiency of DITL in resisting side channel attacks. The DITL design methodology is then applied to design a secure 8051 ALU.

  16. Identification, cloning and characterization of sis7 and sis10 sugar-insensitive mutants of Arabidopsis

    Directory of Open Access Journals (Sweden)

    Biddle Kelly D

    2008-10-01

    Full Text Available Abstract Background The levels of soluble sugars, such as glucose and sucrose, help regulate many plant metabolic, physiological and developmental processes. Genetic screens are helping identify some of the loci involved in plant sugar response and reveal extensive cross-talk between sugar and phytohormone response pathways. Results A forward genetic screen was performed to identify mutants with increased resistance to the inhibitory effects of high levels of exogenous sugars on early Arabidopsis seedling development. The positional cloning and characterization of two of these sugar insensitive (sis mutants, both of which are also involved in abscisic acid (ABA biosynthesis or response, are reported. Plants carrying mutations in SIS7/NCED3/STO1 or SIS10/ABI3 are resistant to the inhibitory effects of high levels of exogenous Glc and Suc. Quantitative RT-PCR analyses indicate transcriptional upregulation of ABA biosynthesis genes by high concentrations of Glc in wild-type germinating seeds. Gene expression profiling revealed that a significant number of genes that are expressed at lower levels in germinating sis7-1/nced3-4/sto1-4 seeds than in wild-type seeds are implicated in auxin biosynthesis or transport, suggesting cross-talk between ABA and auxin response pathways. The degree of sugar insensitivity of different sis10/abi3 mutant seedlings shows a strong positive correlation with their level of ABA insensitivity during seed germination. Conclusion Mutations in the SIS7/NCED3/STO1 gene, which is primarily required for ABA biosynthesis under drought conditions, confer a sugar-insensitive phenotype, indicating that a constitutive role in ABA biosynthesis is not necessary to confer sugar insensitivity. Findings presented here clearly demonstrate that mutations in ABI3 can confer a sugar-insensitive phenotype and help explain previous, mixed reports on this topic by showing that ABA and sugar insensitivity exhibit a strong positive correlation in

  17. Evolving perspectives of the role of novel agents in androgen-independent prostate cancer

    Directory of Open Access Journals (Sweden)

    Sujith Kalmadi

    2008-01-01

    Full Text Available Metastatic androgen-independent prostate cancer presents an intriguing clinical challenge, with a subtle interaction between hormone-responsive and refractory tumor cell elements. The treatment of advanced prostate carcinoma, which had remained stagnant for several decades following the understanding of the link between androgenic stimulation and carcinogenesis, has now started to make steady headway with chemotherapy and targeted approaches. Metastatic prostate cancer is almost always treated with initial androgen deprivation, in various forms. However, despite such treatment androgen-independent prostate cancer cells eventually emerge and progress to threaten life. The therapeutic objectives for treatment of metastatic prostate cancer are to maintain the quality of life and prolong survival. The out-dated nihilistic dogma of deferring chemotherapy until the most advanced stages in advanced prostate cancer is now falling by the wayside with the development of newer effective, tolerable agents.

  18. Prenatal testosterone and theory of mind development: Findings from disorders of sex development.

    Science.gov (United States)

    Khorashad, Behzad S; Khazai, Behnaz; Roshan, Ghasem M; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; van de Grift, Tim C

    2018-03-01

    Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Flexible manipulation of terahertz wave reflection using polarization insensitive coding metasurfaces.

    Science.gov (United States)

    Jiu-Sheng, Li; Ze-Jiang, Zhao; Jian-Quan, Yao

    2017-11-27

    In order to extend to 3-bit encoding, we propose notched-wheel structures as polarization insensitive coding metasurfaces to control terahertz wave reflection and suppress backward scattering. By using a coding sequence of "00110011…" along x-axis direction and 16 × 16 random coding sequence, we investigate the polarization insensitive properties of the coding metasurfaces. By designing the coding sequences of the basic coding elements, the terahertz wave reflection can be flexibly manipulated. Additionally, radar cross section (RCS) reduction in the backward direction is less than -10dB in a wide band. The present approach can offer application for novel terahertz manipulation devices.

  20. Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate

    Directory of Open Access Journals (Sweden)

    Anna Hejmej

    2013-01-01

    Full Text Available To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR and connexin 43 (Cx43 in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20, neonatal (PD2, and prepubertal (PD90 exposure to an antiandrogen flutamide (50 mg/kg bw. In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.