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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. 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: ...

  5. 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, ...

  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. Complete Androgen Insensitivity Syndrome in Three Sisters

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    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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

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

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    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.

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

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    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.

  1. 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.

  2. 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.

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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.

  8. 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.

  9. 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 ...

  10. 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...

  11. 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...

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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 ...

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  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. 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 + ...

  15. 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.

  16. 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.

  17. 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 ...

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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

  13. 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.

  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. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  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. 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.

  5. 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.

  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. 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.

  8. 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.

  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; 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. Abnormalities of the axial and proximal appendicular skeleton in adults with Laron syndrome (growth hormone insensitivity).

    Science.gov (United States)

    Kornreich, L; Konen, O; Schwarz, M; Siegel, Y; Horev, G; Hershkovitz, I; Laron, Z

    2008-02-01

    To investigate abnormalities in the skeleton (with the exclusion of the skull, cervical spine, hands and feet) in patients with Laron syndrome, who have an inborn growth hormone resistance and congenital insulin-like growth factor-1 (IGF-1) deficiency. The study group was composed of 15 untreated patients with Laron syndrome (seven male and eight female) aged 21-68 years. Plain films of the axial and appendicular skeleton were evaluated retrospectively for abnormalities in structure and shape. The cortical width of the long bones was evaluated qualitatively and quantitatively (in the upper humerus and mid-femur), and the cortical index was calculated and compared with published references. Measurements were taken of the mid-anteroposterior and cranio-caudal diameters of the vertebral body and spinous process at L3, the interpedicular distance at L1 and L5, and the sacral slope. Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. The skeleton appeared small in all patients. No signs of osteopenia were visible. The cortex of the long bones appeared thick in the upper limbs in 11 patients and in the lower limbs in four. Compared with the reference values, the cortical width was thicker than average in the humerus and thinner in the femur. The vertebral diameters at L3 and the interpedicular distances at L1 and L5 were significantly smaller in the patients than in the control subjects (PLaron syndrome may be related to a marked retroversion of the humeral head.

  20. 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.

  1. 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

  2. Abnormalities of the axial and proximal appendicular skeleton in adults with Laron syndrome (growth hormone insensitivity)

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L.; Konen, O.; Schwarz, M.; Horev, G. [Schneider Children' s Medical Center of Israel, Imaging Department, Petah Tiqwa (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Siegel, Y. [Rabin Medical Center, Imaging Department, Petah Tiqwa (Israel); Jackson Memorial Hospital, Department of Radiology, Thoracic Section, Miami, FL (United States); Hershkovitz, I. [Tel Aviv University, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv (Israel); Laron, Z. [Schneider Children' s Medical Center of Israel, Endocrinology and Diabetes Research Unit, Petah Tiqwa (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel)

    2008-02-15

    To investigate abnormalities in the skeleton (with the exclusion of the skull, cervical spine, hands and feet) in patients with Laron syndrome, who have an inborn growth hormone resistance and congenital insulin-like growth factor-1 (IGF-1) deficiency. The study group was composed of 15 untreated patients with Laron syndrome (seven male and eight female) aged 21-68 years. Plain films of the axial and appendicular skeleton were evaluated retrospectively for abnormalities in structure and shape. The cortical width of the long bones was evaluated qualitatively and quantitatively (in the upper humerus and mid-femur), and the cortical index was calculated and compared with published references. Measurements were taken of the mid-anteroposterior and cranio-caudal diameters of the vertebral body and spinous process at L3, the interpedicular distance at L1 and L5, and the sacral slope. Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. The skeleton appeared small in all patients. No signs of osteopenia were visible. The cortex of the long bones appeared thick in the upper limbs in 11 patients and in the lower limbs in four. Compared with the reference values, the cortical width was thicker than average in the humerus and thinner in the femur. The vertebral diameters at L3 and the interpedicular distances at L1 and L5 were significantly smaller in the patients than in the control subjects (P < 0.001); however, at L5 the canal was wider, relative to the vertebral body. The study group had a higher rate of anterior osteophytes in the lumbar spine than the controls had, and their osteophytes were also significantly larger. In the six patients for whom radiographs of the upper extremity in its entirety were available on one film, the ulna appeared to be rotated. In one 22-year-old man, multiple epiphyses were still open. Congenital IGF-1 deficiency leads to skeletal abnormalities

  3. Abnormalities of the axial and proximal appendicular skeleton in adults with Laron syndrome (growth hormone insensitivity)

    International Nuclear Information System (INIS)

    Kornreich, L.; Konen, O.; Schwarz, M.; Horev, G.; Siegel, Y.; Hershkovitz, I.; Laron, Z.

    2008-01-01

    To investigate abnormalities in the skeleton (with the exclusion of the skull, cervical spine, hands and feet) in patients with Laron syndrome, who have an inborn growth hormone resistance and congenital insulin-like growth factor-1 (IGF-1) deficiency. The study group was composed of 15 untreated patients with Laron syndrome (seven male and eight female) aged 21-68 years. Plain films of the axial and appendicular skeleton were evaluated retrospectively for abnormalities in structure and shape. The cortical width of the long bones was evaluated qualitatively and quantitatively (in the upper humerus and mid-femur), and the cortical index was calculated and compared with published references. Measurements were taken of the mid-anteroposterior and cranio-caudal diameters of the vertebral body and spinous process at L3, the interpedicular distance at L1 and L5, and the sacral slope. Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. The skeleton appeared small in all patients. No signs of osteopenia were visible. The cortex of the long bones appeared thick in the upper limbs in 11 patients and in the lower limbs in four. Compared with the reference values, the cortical width was thicker than average in the humerus and thinner in the femur. The vertebral diameters at L3 and the interpedicular distances at L1 and L5 were significantly smaller in the patients than in the control subjects (P < 0.001); however, at L5 the canal was wider, relative to the vertebral body. The study group had a higher rate of anterior osteophytes in the lumbar spine than the controls had, and their osteophytes were also significantly larger. In the six patients for whom radiographs of the upper extremity in its entirety were available on one film, the ulna appeared to be rotated. In one 22-year-old man, multiple epiphyses were still open. Congenital IGF-1 deficiency leads to skeletal abnormalities

  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. 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. 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

  7. 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 ...

  8. 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.

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

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    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.

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

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    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. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

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    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.

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

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    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

  18. 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

  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. 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.

  1. 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 ...

  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. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Effect of alendronate on bone mineral density in adult patients with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Eshed, Varda; Benbassat, Carlos A; Laron, Zvi

    2006-04-01

    Severe short stature resulting from a deficiency in insulin-like growth factor-I (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain. The aim of this study was to investigate the action of alendronate on the IGF-I-deficient bones of adult patients with LS and osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5 women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD) 0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11 g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70 mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine, but the difference was not statistically significant (2.3%, p=0.34). Mean total alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007). Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3 nM/mMcre), showed a nonsignificant change during treatment. Our study suggests that treatment with alendronate may have positive effects in patients with LS and low BMD on dual X-ray absorptiometry.

  18. 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)

  19. 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.

  20. Quality of life is reduced in patients with Klinefelter syndrome on androgen replacement therapy

    NARCIS (Netherlands)

    de Ronde, Willem; de Haan, Anne; Drent, Madeleine L

    CONTEXT: Klinefelter syndrome (KS) is a genetic disorder, characterized by an XXY karyotype, hypergonadotrophic hypogonadism and infertility, which affects approximately 1 in 700 men. KS has also been associated with neuropsychological alterations. OBJECTIVE: To investigate whether quality of life

  1. 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.

  2. 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.

  3. 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....

  4. 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.

  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. 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...

  7. 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.

  8. Adrenal androgen excess and body mass index in polycystic ovary syndrome.

    Science.gov (United States)

    Moran, Carlos; Arriaga, Monica; Arechavaleta-Velasco, Fabian; Moran, Segundo

    2015-03-01

    Adrenal hyperandrogenism affects approximately 25% of polycystic ovary syndrome (PCOS) patients but its relation to obesity is not totally understood. This study aimed to assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels in relation to body mass index (BMI) in PCOS. This was a prospective observational study at an institutional practice at an obstetrics/gynecology hospital. The study included 136 PCOS patients, 20-35 years old, and 42 age-matched control women. The participants were classified with the BMI cutoff value of 27 kg/m(2) as follows: 1) high-BMI PCOS patients; 2) low-BMI PCOS patients; 3) high-BMI control women; and 4) low-BMI control women. The data were reanalyzed with the BMI cutoff value of 30 kg/m(2) to corroborate the findings in obese and nonobese patients. Blood samples were taken and LH, FSH, insulin, T, androstenedione (A4), DHEA, DHEAS, and glucose levels were determined. Homeostatic model assessment was calculated. Pelvic and abdominal ultrasound for ovarian morphology and adipose tissue, respectively, were performed. Obese PCOS patients presented significantly more insulin resistance than nonobese PCOS patients. The LH levels and LH/FSH ratio were significantly higher in low-BMI than in high-BMI PCOS patients. The A4 and DHEAS levels were significantly higher in nonobese than in obese PCOS patients. A significant correlation between LH and A4 in nonobese PCOS patients was observed. The frequency of hyperandrogenism by increased A4, and DHEA along with DHEAS was significantly higher in low-BMI PCOS patients compared with high-BMI PCOS patients. Some findings observed with the BMI cutoff value of 27 kg/m(2) changed with the cutoff value of 30 kg/m(2). Low BMI more so than high BMI is associated with increased LH, high A4, DHEA, and DHEAS levels in PCOS patients. The BMI cutoff value of 27 kg/m(2) classified better than 30 kg/m(2) for hormonal and metabolic characteristics.

  9. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society.

    Science.gov (United States)

    Dewailly, Didier; Lujan, Marla E; Carmina, Enrico; Cedars, Marcelle I; Laven, Joop; Norman, Robert J; Escobar-Morreale, Héctor F

    2014-01-01

    BACKGROUND The diagnosis of polycystic ovary syndrome (PCOS) relies on clinical, biological and morphological criteria. With the advent of ultrasonography, follicle excess has become the main aspect of polycystic ovarian morphology (PCOM). Since 2003, most investigators have used a threshold of 12 follicles (measuring 2-9 mm in diameter) per whole ovary, but that now seems obsolete. An increase in ovarian volume (OV) and/or area may also be considered accurate markers of PCOM, yet their utility compared with follicle excess remains unclear. METHODS Published peer-reviewed medical literature about PCOM was searched using PubMed.gov online facilities and was submitted to critical assessment by a panel of experts. Studies reporting antral follicle counts (AFC) or follicle number per ovary (FNPO) using transvaginal ultrasonography in healthy women of reproductive age were also included. Only studies that reported the mean or median AFC or FNPO of follicles measuring 2-9 mm, 2-10 mm or definitions of PCOM among studies, this question cannot be answered with absolute certainty. CONCLUSIONS The Task Force recommends using FNPO for the definition of PCOM setting the threshold at ≥25, but only when using newer technology that affords maximal resolution of ovarian follicles (i.e. transducer frequency ≥8 MHz). If such technology is not available, we recommend using OV rather than FNPO for the diagnosis of PCOM for routine daily practice but not for research studies that require the precise full characterization of patients. The Task Force recognizes the still unmet need for standardization of the follicle counting technique and the need for regularly updating the thresholds used to define follicle excess, particularly in diverse populations. Serum AMH concentration generated great expectations as a surrogate marker for the follicle excess of PCOM, but full standardization of AMH assays is needed before they can be routinely used for clinical practice and research. Finally

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Dietary cranberry, blueberry, and black raspberry affects the development of dyslipidemia and insulin insensitivity associated with metabolic syndrome in high fructose fed rats

    Science.gov (United States)

    Effects of feeding cranberry, blueberry, and black raspberry powder on selected parameters of metabolic syndrome were investigated in 40 growing male Sprague Dawley rats. Animals were divided into five dietary treatments of 1) control AIN93G diet, 2) high fructose (65% by weight, HF) diet, and 3-5) ...

  18. 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.

  19. Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Anastasia, Karela; Koika, Vasiliki; Roupas, Nikolaos D; Armeni, Anastasia; Marioli, Dimitra; Panidis, Dimitrios; George, Adonakis; Georgopoulos, Neoklis A

    2015-01-01

    To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

  20. Effects of insulin-like growth factor-I deficiency and replacement therapy on the hematopoietic system in patients with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Sivan, Bezalel; Lilos, Pearl; Laron, Zvi

    2003-01-01

    Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in Laron syndrome (LS), are a unique model in man to study the consequences resulting from defects in growth hormone (GH) signal transmission. To assess retrospectively the effect of IGF-I deficiency and its therapy on the various cells of the hematopoietic system as reflected by peripheral blood counts. Two groups of patients were studied. The first group consisted of 11 untreated patients with LS, seven males and four females, who were followed from childhood into adult age. Average age at the time of data analysis was 45.4 +/- 9.6 years. The second group included ten children with LS, six males and four females, who received IGF-I replacement therapy for an average period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or more were included in the analysis. Data on blood counts were collected from the patients' charts. Blood samples were drawn at baseline, weekly during the first month, once a month during the first year, and once every 3 months thereafter. Statistical analysis of the change over time was performed using repeated measures ANOVA. Children with LS had red cell indices in the lower normal range and an elevated monocyte count. A statistically significant rise in red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl to 13.01 g/dl (p syndrome, confirms that IGF-I has a strong stimulatory effect on erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and platelets, an effect not previously described. The mechanism by which IGF-I mediates these effects needs further elucidation.

  1. Immunoexpression of androgen receptor and nine markers of maturation in the testes of adolescent boys with Klinefelter syndrome

    DEFF Research Database (Denmark)

    Wikström, Anne M; Hoei-Hansen, Christina E; Dunkel, Leo

    2007-01-01

    CONTEXT: The pathogenesis and mechanisms behind the degeneration of the seminiferous tubules in testes of subjects with Klinefelter syndrome (KS) are yet unknown. OBJECTIVE: The objective of this prospective clinical study was to characterize the testicular degeneration process during puberty in ...

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

    OpenAIRE

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

    2016-01-01

    Abstract 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 ...

  3. 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.

  4. 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.

  5. 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 ...

  6. 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.

  7. Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

    Science.gov (United States)

    Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

    2017-12-01

    Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

  8. 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 ...

  9. 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.

  10. Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

    Science.gov (United States)

    Dawson, Jacqueline K; Dorff, Tanya B; Todd Schroeder, E; Lane, Christianne J; Gross, Mitchell E; Dieli-Conwright, Christina M

    2018-04-03

    Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day - 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m 2 ), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and

  11. Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial.

    Science.gov (United States)

    Azadi-Yazdi, M; Karimi-Zarchi, M; Salehi-Abargouei, A; Fallahzadeh, H; Nadjarzadeh, A

    2017-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m -2 versus -1.69 (0.20) kg m -2 , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL -1 versus -1.02 (0.72) ng mL -1 , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L -1 , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG. © 2016 The British Dietetic Association Ltd.

  12. 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

  13. 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

  14. Androgen Excess- Polycystic Ovary Syndrome Society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome.

    Science.gov (United States)

    Dokras, Anuja; Stener-Victorin, Elisabeth; Yildiz, Bulent O; Li, Rong; Ottey, Sasha; Shah, Duru; Epperson, Neill; Teede, Helena

    2018-05-01

    To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with polycystic ovary syndrome (PCOS) and review prevalence based on phenotypes and ethnicity, changes over time, etiology, and impact of treatment. Systematic reviews and preparation of position statement. Not applicable. Women with PCOS and controls screened using validated tools. None. Depressive symptoms, anxiety symptoms, disordered eating, and HRQoL scores. Several studies demonstrate that women with PCOS have an increased prevalence of higher depression and anxiety scores and higher odds of moderate and severe depressive and anxiety symptoms compared with controls. Obesity, hyperandrogenism, and fertility have a weak association with these symptoms. HRQoL scores are consistently reduced in PCOS, with infertility and weight concerns having the most significant impact. Some studies suggest an increased prevalence of disordered eating in women with PCOS compared with controls. The few studies that have evaluated the impact of PCOS-related treatments (lifestyle interventions and pharmacotherapy) show no detrimental effect or some improvement in depressive and anxiety symptoms and HRQoL scores. In women with PCOS, screening for depressive and anxiety symptoms should be offered at the time of diagnosis and screening for disordered eating should be considered. Further research is required across PCOS phenotypes, in longitudinal cohorts and on impact of therapy on depressive and anxiety syptoms, HRQOL, and disordered eating. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. 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

  16. 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

  17. [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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. The Pragmatics of Insensitive Assessments

    Directory of Open Access Journals (Sweden)

    Alexander Almér

    2010-12-01

    Full Text Available In assessing the veridicality of utterances, we normally seem to assess the satisfaction of conditions that the speaker had been concerned to get right in making the utterance. However, the debate about assessor-relativism about epistemic modals, predicates of taste, gradable adjectives and conditionals has been largely driven by cases in which seemingly felicitous assessments of utterances are insensitive to aspects of the context of utterance that were highly relevant to the speaker’s choice of words.In this paper, we offer an explanation of why certain locutions invite insensitive assessments, focusing primarily on ’tasty’ and ’might’. We spell out some reasons why felicitous insensitive assessments are puzzling and argue briefly that recent attempts to accommodate such assessments (including attempts by John MacFarlane, Kai von Fintel and Anthony Gillies all fail to provide more than hints at a solution to the puzzle. In the main part of the paper, we develop an account of felicitous insensitive assessments by identifying a number of pragmatic factors that influence the felicity of assessments. Before closing, we argue that the role of these factors extends beyond cases considered in the debate about assessor-relativism and fits comfortably with standard contextualist analyses of the relevant locutions.ReferencesAlmér, A. & Björnsson, G. 2009. ‘Relativism, Contextualism and Insensitive Assessments’. Logique et Analyse 52: 363–372.Bach, K. 2011. ‘Perspectives on possibilities: Contextualism, Relativism, or what?’Bennett, J. 2003. A Philosophical Guide to Conditionals. Oxford U. P.http://dx.doi.org/10.1093/0199258872.001.0001Björnsson, G. 2011. ‘Towards a Radically Pragmatic Theory of If-Conditionals’. Forthcoming in Making Semantics Pragmatic, (ed Ken Turner, in Current Research in the Semantics/Pragmatics Interface, Vol 24, Emerald.Björnsson, G. ms. ‘Do “Objectivist” Features of Moral Discourse and Thinking

  7. 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

  8. 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.

  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. 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.

  11. Anti-androgenic activity of Nardostachys jatamansi DC and Tribulus terrestris L. and their beneficial effects on polycystic ovary syndrome-induced rat models

    NARCIS (Netherlands)

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

    2015-01-01

    Background: 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

  12. A functional anti-müllerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients

    NARCIS (Netherlands)

    M.E. Kevenaar (Marlies); J.S.E. Laven (Joop); S. Lie Fong (Sharon); A.G. Uitterlinden (André); F.H. de Jong (Frank); A.P.N. Themmen (Axel); J.A. Visser (Jenny)

    2008-01-01

    textabstractContext: The common characteristic of polycystic ovary syndrome (PCOS) is a disturbance in the selection of the dominant follicle, resulting in anovulation. In PCOS women, serum anti-Müllerian hormone (AMH) levels are elevated. Because AMH decreases FSH sensitivity in mice, the elevated

  13. 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.

  14. 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.

  15. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.

    Science.gov (United States)

    Panidis, Dimitrios; Farmakiotis, Dimitrios; Rousso, David; Kourtis, Anargyros; Katsikis, Ilias; Krassas, Gerassimos

    2008-04-01

    To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. Prospective clinical study. Department of obstetrics and gynecology in a major university in Greece. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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…

  2. Síndrome de insuficiência androgênica: critérios diagnósticos e terapêuticos Androgen insufficiency syndrome: diagnostic and therapeutic criteria

    Directory of Open Access Journals (Sweden)

    César Eduardo Fernandes

    2006-01-01

    Full Text Available A síndrome da insuficiência androgênica na mulher (SIA desperta, mesmo nos dias atuais, muitas discussões e encerra muitas controvérsias. Sabe-se, no entanto, que os níveis plasmáticos de testosterona declinam progressivamente ao longo do período reprodutivo. Conceitua-se a SIA como o conjunto de sintomas clínicos, a presença de biodisponibilidade diminuída de testosterona e os níveis normais de estrogênios. Entre os principais sintomas, citam-se o comprometimento do bem-estar, o humor disfórico, a fadiga sem causa aparente, o comprometimento do desejo sexual, o emagrecimento e a instabilidade vasomotora em mulheres pós-menopáusicas sob terapêutica estrogênica. Esses sintomas, no entanto, são potencialmente atribuíveis a diferentes etiologias e dificultam o correto diagnóstico na maioria dos casos, ainda que ele seja lembrado com freqüência em pacientes que se submetem à ooforectomia bilateral. O diagnóstico da SIA parece ser essencialmente clínico, não havendo a necessidade das dosagens laboratoriais para a sua comprovação. Não se deve indicar a terapêutica androgênica (TA em pacientes que não estejam adequadamente estrogenizadas. Considera-se a testosterona o hormônio ideal para a TA. As pacientes com sintomas sugestivos de SIA, excluídas outras causas identificáveis, especialmente se pós-menopáusicas, são candidatas à TA. Não existem dados de segurança sobre a TA em usuárias em longo prazo. A via transdérmica - através de adesivos, cremes e gel - parece ser preferível à oral.The women’s androgen insufficiency syndrome (AIS arises, even nowadays, many debates and clears a lot of controversies. It is known, however, that the plasmatic levels of testosterone gradually decline through the reproductive period. AIS is appraised as a set of clinical symptoms, bioavailability presence diminished of testosterone and normal levels of estrogen. Among the main symptoms that remind the diagnosis are the

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. 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?«

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. Anaesthesia and familial dysautonomia with congenital insensitivity ...

    African Journals Online (AJOL)

    Adele

    the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital ... sion, and excessive vagal reflexes. Central ... His skin was mottled, dry and pale. ... Eye protection is important since affected individuals lack tears,.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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 2.

    Science.gov (United States)

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

    2015-12-01

    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 and the Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014. Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which insulin resistance or insulin give rise to oligomenorrhea and hyperandrogenemia, however, is unclear. Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of insulin resistance. Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis. Given the association with insulin resistance, all women with PCOS require evaluation for the risk of metabolic syndrome (MetS) and its components, including type 2 diabetes, hypertension, hyperlipidemia, and the possible risk of clinical events, including acute myocardial infarction and stroke. Obese women with PCOS are at increased risk for MetS with impaired glucose tolerance (IGT; 31 to 35%) and type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years. Data suggest the need for baseline oral glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT. Compared with BMI- and age-matched controls, young, lean PCOS women have lower high-density lipoprotein (HDL) size, higher very-low-density lipoprotein particle number, higher low-density lipoprotein (LDL) particle number, and borderline lower LDL size. Statins have been shown to lower testosterone levels either alone or in combination with oral

  1. 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.

  2. Motion-insensitive rapid configuration relaxometry.

    Science.gov (United States)

    Nguyen, Damien; Bieri, Oliver

    2017-08-01

    Triple echo steady state (TESS) uses the lowest steady state configuration modes for rapid relaxometry. Due to its unbalanced gradient scheme, however, TESS is inherently motion-sensitive. The purpose of this work is to merge TESS with a balanced acquisition scheme for motion-insensitive rapid configuration relaxometry, termed MIRACLE. The lowest order steady state free precession (SSFP) configurations are retrieved by Fourier transformation of the frequency response of N frequency-shifted balanced SSFP (bSSFP) scans and subsequently processed for relaxometry, as proposed with TESS. Accuracy of MIRACLE is evaluated from simulations, phantom studies as well as in vivo brain and cartilage imaging at 3T. Simulations and phantom results revealed no conceptual flaw, and artifact-free configuration imaging was achieved in vivo. Overall, relaxometry results were accurate in phantoms and in good agreement for cartilage and for T2 in the brain, but apparent low T1 values were observed for brain white matter; reflecting asymmetries in the bSSFP profile. Rapid T1 and T2 mapping with MIRACLE offers analogous properties as TESS while successfully mitigating its motion-sensitivity. As a result of the Fourier transformation, relaxometry becomes sensitive to the voxel frequency distribution, which may contain useful physiologic information, such as structural brain integrity. © 2016 International Society for Magnetic Resonance in Medicine. Magn Reson Med 78:518-526, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  3. 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

  4. 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.

  5. Growth hormone insensitivity: Mexican case report

    Science.gov (United States)

    De Ita, J R; Aguirre, G A; García–Magariño, M; Martín-Estal, I; Lara-Diaz, V J; Elizondo, M I

    2017-01-01

    Herein, we present a 14-year-old patient with short stature (134 cm) referred from Paediatrics to our department for complementary evaluation since growth hormone (GH) treatment failed to show any improvement. He was born premature and small for gestational age. Genital examination classified the patient as Tanner I–II with small penis and testicular size for his age. Biochemical analyses revealed normal GH levels with low serum insulin-like growth factor-1 (IGF-1). Molecular diagnosis confirmed several mutations in IGF1R and IGFALS, and so he was diagnosed with Laron Syndrome or GH insensibility and treated with IGF-1 substitutive therapy. Learning points: Evaluation of the GH/IGF-1 axis when short stature does not respond to conservative treatment must be included in the ordinary practice. Laron Syndrome real incidence should be calculated once undiagnosed cases arise, as treatment, due to lack of market, is unaffordable. Even when adulthood is reached, and no longitudinal growth can be achieved, still IGF-1 treatment in Laron Syndrome patients should be pursued as metabolic and protective derangements could arise. PMID:29147569

  6. 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.

  7. 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.

  8. 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.

  9. Growth hormone insensitivity: Mexican case report

    Directory of Open Access Journals (Sweden)

    I Castilla-Cortazar

    2017-11-01

    Full Text Available Herein, we present a 14-year-old patient with short stature (134 cm referred from Paediatrics to our department for complementary evaluation since growth hormone (GH treatment failed to show any improvement. He was born premature and small for gestational age. Genital examination classified the patient as Tanner I–II with small penis and testicular size for his age. Biochemical analyses revealed normal GH levels with low serum insulin-like growth factor-1 (IGF-1. Molecular diagnosis confirmed several mutations in IGF1R and IGFALS, and so he was diagnosed with Laron Syndrome or GH insensibility and treated with IGF-1 substitutive therapy.

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. 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

  20. 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

  1. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term...... '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...

  2. 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.

  3. 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

  4. 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.

  5. 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...

  6. Recent developments in bend-insensitive and ultra-bend-insensitive fibers

    Science.gov (United States)

    Boivin, David; de Montmorillon, Louis-Anne; Provost, Lionel; Montaigne, Nelly; Gooijer, Frans; Aldea, Eugen; Jensma, Jaap; Sillard, Pierre

    2010-02-01

    Designed to overcome the limitations in case of extreme bending conditions, Bend- and Ultra-Bend-Insensitive Fibers (BIFs and UBIFs) appear as ideal solutions for use in FTTH networks and in components, pigtails or patch-cords for ever demanding applications such as military or sensing. Recently, however, questions have been raised concerning the Multi-Path-Interference (MPI) levels in these fibers. Indeed, they are potentially subject to interferences between the fundamental mode and the higher-order mode that is also bend resistant. This MPI is generated because of discrete discontinuities such as staples, bends and splices/connections that occur on distance scales that become comparable to the laser coherent length. In this paper, we will demonstrate the high MPI tolerance of all-solid single-trench-assisted BIFs and UBIFs. We will present the first comprehensive study combining theoretical and experimental points of view to quantify the impact of fusion splices on coherent MPI. To be complete, results for mechanical splices will also be reported. Finally, we will show how the single-trench- assisted concept combined with the versatile PCVD process allows to tightly control the distributions of fibers characteristics. Such controls are needed to massively produce BIFs and to meet the more stringent specifications of the UBIFs.

  7. 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.

  8. 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.

  9. Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines.

    Science.gov (United States)

    Shaikhibrahim, Zaki; Lindstrot, Andreas; Ochsenfahrt, Jacqueline; Fuchs, Kerstin; Wernert, Nicolas

    2013-01-01

    Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. ABUSE OF ANABOLIC ANDROGENIC STEROIDS

    Directory of Open Access Journals (Sweden)

    Abbas Yavari

    2009-09-01

    Full Text Available According to the International Olympic Committee, the abuse of anabolic androgenic steroids (AASS is found in over 50% of positive doping tests. AASS abuse is not restricted to the organized sports andwidespread use. It remains as an unsolved public-health problem.Lower black market price, easier access to AASS, bodybuilding clubs and internet advertising are factors of this increasingly misuse. There is not real data about the prevalence of AASS abuse in various populations or countries, because most of athletes or students, due to their prohibition or ethical aspects do not admit to AASS abuse. Often they are aware of the risks of their choice and yet, are eager to put themselves at risk without deeper consideration. The abusers use them to improve their physical fitness and appearance.Present article has been collected to elucidate the risks and adverse effects of AASS and explanation of mechanisms of these events.

  3. 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.

  4. 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

  5. Design of delay insensitive circuits using multi-ring structures

    DEFF Research Database (Denmark)

    Sparsø, Jens; Staunstrup, Jørgen; Dantzer-Sørensen, Michael

    1992-01-01

    The design and VLSI implementation of a delay insensitive circuit that computes the inner product of two vec·tors is described. The circuit is based on an iterative serial-parallel multiplication algorithm. The design is based on a data flow approach using pipelines and rings that are combined...

  6. Gender insensitivity and male bias in local advertising | Mate ...

    African Journals Online (AJOL)

    Gender insensitivity and male bias in local advertising. Rekopantswe Mate. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/safere.v3i1.23952 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  7. A Novel Mechanism of Androgen Receptor Action

    National Research Council Canada - National Science Library

    Roberts, Jr, Charles T

    2006-01-01

    .... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

  8. 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.

  9. 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.

  10. Participação dos androgênios adrenais na síndrome dos ovários policísticos Adrenal androgen participation in the polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Angelo Barrionuevo Gil Junior

    2010-11-01

    thyroxine, insulin, total testosterone, SHBG, and free androgen index were measured. Insulin resistance was considered to be present with a homeostatic model assessment index >2.8. The adrenal response to cortrosyn was assessed by the hormonal rise observed at 60 minutes, and by the area under the response curve. RESULTS: biochemical hyperandrogenism was found in 43 of 53 eligible patients (81.1%. Thirty-three women had adrenal hyperandrogenism (62.2%. The weight of these 33 women, aging 25.1±5.0 years, was 74.9±14.9 kg, BMI was 28.8±6.0 and the waist/hip ratio was 0.8±0.1. DHEAS was >6.7 nmol/L in 13 (39.4% and androstenendione was >8.7 nmol/L in 31 (93.9%. The increments in 17-OHP4, cortisol, A, and progesterone were 163%, 153%, 32%, and 79%, respectively. The homeostatic insulin resistance model was >2.8 in 14 (42.4%. Insulin and estradiol were not correlated with cortisol or androgens. CONCLUSIONS: the use of multiple endocrine parameters showed a high prevalence of biochemical hyperandrogenism in patients with PCOS. Two thirds of the patients had adrenal hyperandrogenism, and estradiol and insulin did not influence adrenal secretion.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. Evidence of auditory insensitivity to vocalization frequencies in two frogs

    DEFF Research Database (Denmark)

    Goutte, Sandra; Mason, Matthew J; Christensen-Dalsgaard, Jakob

    2017-01-01

    discrimination from background noise and heterospecific calls. However, we present here evidence that two anurans, Brachycephalus ephippium and B. pitanga, are insensitive to the sound of their own calls. Both species produce advertisement calls outside their hearing sensitivity range and their inner ears...... by their high toxicity might help to explain why calling has not yet disappeared, and that visual communication may have replaced auditory in these colourful, diurnal frogs....

  18. Androgen receptor drives cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yelena Mirochnik

    Full Text Available The accepted androgen receptor (AR role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

  19. 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....

  20. 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.

  1. 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.

  2. 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.

  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. 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

  5. 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...

  6. 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.

  7. 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.

  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. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Temperature-insensitive laser frequency locking near absorption lines

    International Nuclear Information System (INIS)

    Kostinski, Natalie; Olsen, Ben A.; Marsland, Robert III; McGuyer, Bart H.; Happer, William

    2011-01-01

    Combined magnetically induced circular dichroism and Faraday rotation of an atomic vapor are used to develop a variant of the dichroic atomic vapor laser lock that eliminates lock sensitivity to temperature fluctuations of the cell. Operating conditions that eliminate first-order sensitivity to temperature fluctuations can be determined by low-frequency temperature modulation. This temperature-insensitive gyrotropic laser lock can be accurately understood with a simple model, that is in excellent agreement with observations in potassium vapor at laser frequencies in a 2 GHz range about the 770.1 nm absorption line. The methods can be readily adapted for other absorption lines.

  17. 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...

  18. 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.

  19. 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

  20. 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.

  1. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela

    2003-01-01

    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  2. Therapeutic Use of Androgens in Women

    Science.gov (United States)

    ... in men, the same is not true for women. Media stories about how testosterone increases libido (sexual desire) ... medications, do have lower androgen levels than healthy women. In addition, despite claims in the popular media that getting testosterone levels checked is “a small ...

  3. 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.

  4. 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.

  5. [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.

  6. 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

  7. 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.

  8. 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

  9. Humidity insensitive TOPAS polymer fiber Bragg grating sensor

    DEFF Research Database (Denmark)

    Yuan, Scott Wu; Khan, Lutul; Webb, David J.

    2011-01-01

    We report the first experimental demonstration of a humidity insensitive polymer optical fiber Bragg grating (FBG), as well as the first FBG recorded in a TOPAS polymer optical fiber in the important low loss 850nm spectral region. For the demonstration we have fabricated FBGs with resonance...... wavelength around 850 nm and 1550 nm in single-mode microstructured polymer optical fibers made of TOPAS and the conventional poly (methyl methacrylate) (PMMA). Characterization of the FBGs shows that the TOPAS FBG is more than 50 times less sensitive to humidity than the conventional PMMA FBG in both...... wavelength regimes. This makes the TOPAS FBG very appealing for sensing applications as it appears to solve the humidity sensitivity problem suffered by the PMMA FBG....

  10. Temperature-insensitive fiber Bragg grating dynamic pressure sensing system.

    Science.gov (United States)

    Guo, Tuan; Zhao, Qida; Zhang, Hao; Zhang, Chunshu; Huang, Guiling; Xue, Lifang; Dong, Xiaoyi

    2006-08-01

    Temperature-insensitive dynamic pressure measurement using a single fiber Bragg grating (FBG) based on reflection spectrum bandwidth modulation and optical power detection is proposed. A specifically designed double-hole cantilever beam is used to provide a pressure-induced axial strain gradient along the sensing FBG and is also used to modulate the reflection bandwidth of the grating. The bandwidth modulation is immune to spatially uniform temperature effects, and the pressure can be unambiguously determined by measuring the reflected optical power, avoiding the complex wavelength interrogation system. The system acquisition time is up to 85 Hz for dynamic pressure measurement, and the thermal fluctuation is kept less than 1.2% full-scale for a temperature range of -10 degrees C to 80 degrees C.

  11. 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.

  12. 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).

  13. 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

  14. 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

  15. 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.

  16. 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

  17. The Role of (BETA)-Catenin in Androgen Receptor Signaling

    National Research Council Canada - National Science Library

    Bhowmick, Neil A

    2006-01-01

    .... Our preliminary data seem indicate stromally derived paracrine Wnt family members activate theepithelial frizzled receptor to enable prostate epithelial survival in an androgen deficient environment...

  18. 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.

  19. 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

  20. 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...

  1. 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...

  2. 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

  3. 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

  4. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigaby, James

    2003-01-01

    The purpose of this project is to examine the nature and severity of cognitive impairments experienced by men undergoing continuous androgen deprivation or intermittent androgen deprivation treatment...

  5. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigsby, James

    2004-01-01

    The purpose of this project is to examine the nature and severity of cognitive impairments experienced by men undergoing continuous androgen deprivation or intermittent androgen deprivation treatment...

  6. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigsby, James P; Brega, Angela G

    2006-01-01

    The purpose of this project was to examine the nature and severity of cognitive impairments experienced by men undergoing continuous androgen deprivation or intermittent androgen deprivation treatment (ADT...

  7. 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.

  8. 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.

  9. Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Geel, Tessa M. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Meiss, Gregor [Institute of Biochemistry, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Gun, Bernardina T. van der; Kroesen, Bart Jan; Leij, Lou F. de [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Zaremba, Mindaugas; Silanskas, Arunas [Institute of Biotechnology, Vilnius LT-02241 (Lithuania); Kokkinidis, Michael [IMBB/FORTH and University of Crete/Department of Biology, GR-71409 Heraklion/Crete (Greece); Pingoud, Alfred [Institute of Biochemistry, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Ruiters, Marcel H. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Synvolux therapeutics, Groningen (Netherlands); McLaughlin, Pamela M. [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands); Rots, Marianne G., E-mail: m.g.rots@med.umcg.nl [Department of Pathology and Medical Biology, Groningen University Institute for Drug Exploration (GUIDE), University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen (Netherlands)

    2009-09-10

    TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restriction endonucleases to directly digest DNA in vivo, thereby circumventing the caspase cascade. For this purpose, we delivered enzymatically active endonucleases via the cationic amphiphilic lipid SAINT-18{sup Registered-Sign }:DOPE to both TRAIL-sensitive and insensitive ovarian carcinoma cells (OVCAR and SKOV-3, respectively). Functional nuclear localization after delivery of various endonucleases (BfiI, PvuII and NucA) was indicated by confocal microscopy and genomic cleavage analysis. For PvuII, analysis of mitochondrial damage demonstrated extensive apoptosis both in SKOV-3 and OVCAR. This study clearly demonstrates that cellular delivery of restriction endonucleases holds promise to serve as a novel therapeutic tool for the treatment of resistant ovarian carcinomas.

  10. 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.

  11. 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.

  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. 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.

  14. 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...

  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. 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.

  17. 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 ...

  18. Myocardial infarction, androgen and the skin.

    Science.gov (United States)

    Halim, M M; Meyrick, G; Jeans, W D; Murphy, D; Burton, J L

    1978-01-01

    Various indices of masculinity were compared in 48 men who had recovered from myocardial infarction and in their age-matched controls. We found little evidence to support the idea that myocardial infarction is related to increased androgenic stimulation. The patients with myocardial infarction had no increase in plasma testosterone, muscle thickness, sebum excretion rate, maximal sweat secretion rate, male pattern alopecia or density of terminal body hair, but as a group they had a slight increase in skin and bone thickness compared with the controls.

  19. Embodied masculinity and androgen deprivation therapy.

    Science.gov (United States)

    Oliffe, John

    2006-05-01

    This paper describes the findings from an ethnographic study of 16 Anglo-Australian men treated with androgen deprivation therapy (ADT) for advanced prostate cancer. Utilising a social constructionist gendered analysis, participants' experiences, particularly in relation to embodied masculinity, are described in the context of reduced testosterone that accompany ADT. The findings indicated that participants reformulated many ideals of hegemonic masculinity in response to functional body changes. However, hegemonic masculinity strongly influenced participants' philosophical resolve to "fight" prostate cancer. The findings are considered in broader ongoing debates about essentialist sex and the social construction of gender.

  20. 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.

  1. 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

  2. Effects of androgenic-anabolic steroids in athletes.

    Science.gov (United States)

    Hartgens, Fred; Kuipers, Harm

    2004-01-01

    . Generally, AAS seem to induce increments of aggression and hostility. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose and drug dependent. AAS dependence or withdrawal effects (such as depression) seem to occur only in a small number of AAS users. Dissatisfaction with the body and low self-esteem may lead to the so-called 'reverse anorexia syndrome' that predisposes to the start of AAS use. Many other adverse effects have been associated with AAS misuse, including disturbance of endocrine and immune function, alterations of sebaceous system and skin, changes of haemostatic system and urogenital tract. One has to keep in mind that the scientific data may underestimate the actual untoward effects because of the relatively low doses administered in those studies, since they do not approximate doses used by illicit steroid users. The mechanism of action of AAS may differ between compounds because of variations in the steroid molecule and affinity to androgen receptors. Several pathways of action have been recognised. The enzyme 5-alpha-reductase seems to play an important role by converting AAS into dihydrotestosterone (androstanolone) that acts in the cell nucleus of target organs, such as male accessory glands, skin and prostate. Other mechanisms comprises mediation by the enzyme aromatase that converts AAS in female sex hormones (estradiol and estrone), antagonistic action to estrogens and a competitive antagonism to the glucocorticoid receptors. Furthermore, AAS stimulate erythropoietin synthesis and red cell production as well as bone formation but counteract bone breakdown. The effects on the cardiovascular system are proposed to be mediated by the occurrence of AAS-induced atherosclerosis (due to unfavourable influence on serum lipids and lipoproteins), thrombosis, vasospasm or direct injury to vessel walls, or may be ascribed to a combination of the different mechanisms. AAS-induced increment of muscle tissue can be attributed

  3. 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.

  4. 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

  5. Androgens and estrogens in skeletal sexual dimorphism

    Directory of Open Access Journals (Sweden)

    Michaël Laurent

    2014-04-01

    Full Text Available Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T to estradiol (E2 by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis.

  6. Androgens and estrogens in skeletal sexual dimorphism

    Science.gov (United States)

    Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

    2014-01-01

    Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

  7. 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...

  8. [Syndrome X vs metabolic syndrome].

    Science.gov (United States)

    Morales Villegas, Enrique

    2006-01-01

    Himsworth in 1939 postulated that Diabetes Mellitus type 2 (DM2) was not only an insulin deficiency state but also a cellular insulin insensitivity disease. Thirty years later, DeFronzo and Reaven demonstrated that insulin resistance (IR) preceded and predisposed for DM2 and atherosclerotic-cardiovascular-disease (ACVD). Reaven was the first to point out the relationship between IR and with hyperglycemia, dyslipidosis, and hypertension as mediators for ACVD, creating the concept of Syndrome X (SX) in 1988. WHO and, thereafter, other medical societies and medical groups, mainly ATP-III, in 2002, based on the difficulty of diagnosing IR in a simple, reliable, and inexpensive way, proposed and published the Metabolic Syndrome (MS) concept, as a group of five variables, i.e., obesity, hyperglycemia, hypertriglyceridemia, low HDL, and hypertension, as an easy clinical approximation to suspect and treat an increased cardiometabolic risk. Nowadays, there are deep and extensive controversies on this issue; however, these controversies do not really exist since all discordant points of view are rather quantitative and not qualitative in nature. This article is aimed at differentiating and harmonizing the complementary concepts of SX and MS, at analyzing why MS is a good "clinical window" to look for IR and its underlying manifestations, and finally to accept that the MS concept complements, but does not substitute or antagonize, traditional scales used to asses cardiovascular risk, such as the Framingham scale.

  9. Heating-insensitive scale increase caused by convective precipitation

    Science.gov (United States)

    Haerter, Jan; Moseley, Christopher; Berg, Peter

    2017-04-01

    The origin of intense convective extremes and their unusual temperature dependence has recently challenged traditional thermodynamic arguments, based on the Clausius-Clapeyron relation. In a sequence of studies (Lenderink and v. Mejgaard, Nat Geosc, 2008; Berg, Haerter, Moseley, Nat Geosc, 2013; and Moseley, Hohenegger, Berg, Haerter, Nat Geosc, 2016) the argument of convective-type precipitation overcoming the 7%/K increase in extremes by dynamical, rather than thermodynamic, processes has been promoted. How can the role of dynamical processes be approached for precipitating convective cloud? One-phase, non-precipitating Rayleigh-Bénard convection is a classical problem in complex systems science. When a fluid between two horizontal plates is sufficiently heated from below, convective rolls spontaneously form. In shallow, non-precipitating atmospheric convection, rolls are also known to form under specific conditions, with horizontal scales roughly proportional to the boundary layer height. Here we explore within idealized large-eddy simulations, how the scale of convection is modified, when precipitation sets in and intensifies in the course of diurnal solar heating. Before onset of precipitation, Bénard cells with relatively constant diameter form, roughly on the scale of the atmospheric boundary layer. We find that the onset of precipitation then signals an approximately linear (in time) increase in horizontal scale. This scale increase progresses at a speed which is rather insensitive to changes in surface temperature or changes in the rate at which boundary conditions change, hinting at spatial characteristics, rather than temperature, as a possible control on spatial scales of convection. When exploring the depth of spatial correlations, we find that precipitation onset causes a sudden disruption of order and a subsequent complete disintegration of organization —until precipitation eventually ceases. Returning to the initial question of convective

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  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. 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.

  17. 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.

  18. Early androgen exposure and human gender development.

    Science.gov (United States)

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  19. 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.

  20. 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....

  1. 40 Gbit/s NRZ Packet-Length Insensitive Header Extraction for Optical Label Switching Networks

    DEFF Research Database (Denmark)

    Seoane, Jorge; Kehayas, E; Avramopoulos, H.

    2006-01-01

    A simple method for 40 Gbit/s NRZ header extraction based on envelope detection for optical label switching networks is presented. The scheme is insensitive to packet length and spacing and can be single-chip integrated cost-effectively......A simple method for 40 Gbit/s NRZ header extraction based on envelope detection for optical label switching networks is presented. The scheme is insensitive to packet length and spacing and can be single-chip integrated cost-effectively...

  2. 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....

  3. 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

  4. 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.

  5. Steroidogenic alterations and adrenal androgen excess in PCOS.

    Science.gov (United States)

    Doi, Suhail A R; Al-Zaid, Mona; Towers, Philip A; Scott, Christopher J; Al-Shoumer, Kamal A S

    2006-09-01

    This cross-sectional study was undertaken to improve our understanding of the steroidogenic alterations leading to adrenal hyperandrogenism in polycystic ovarian syndrome (PCOS). Two-hundred and thirty-four women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. We used the androstenedione/DHEAS ratio as a surrogate for the level of ovarian 3betaHSD activity. We then selected the 90th percentile for the ratio in those with elevated DHEAS (>9 micromol/l) as the cut-off level beyond which excess DHEAS production will be minimized by excess ovarian 3betaHSD activity. This cut-off level was at a ratio of 1.5 and all PCOS women were then divided into two groups, the higher (>1.5) being the group with excess ovarian 3betaHSD activity. We hypothesized that women with a high ratio would be unlikely to have DHEAS excess due to the rapid conversion of DHEA to androstenedione. Those with a low ratio (concordant ovarian and adrenal steroidogenesis) could then either have high DHEAS or normal DHEAS, depending on whether CYP17 activity was higher or lower respectively. Insulin resistance was found to be associated with decreased CYP17 activity while irregular cycles and neuroendocrine dysfunction were determined to be associated with higher ovarian 3betaHSD activity. Adrenal androgen excess in PCOS seems to be related to insulin sensitivity as well as decreased activity of 3betaHSD, the latter being preferentially present in those women with regular cycles or without neuroendocrine dysfunction.

  6. 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

  7. 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

  8. Androgenic alopecia in women: an Indian perspective.

    Science.gov (United States)

    Sehgal, Virendra N; Srivastava, Govind; Aggarwal, Ashok K; Midha, Reshmi

    2013-01-01

    The authors sought to investigate androgenic alopecia (AA) utilizing clinical and investigative procedures to establish the pattern of AA in the Indian subcontinent. A total of 35 consecutive women presenting with AA were included. After obtaining informed consent, a detailed history/examination, hair pull test, trichogram, and a scalp biopsy were performed in patients. AA classification was attempted across Ludwig and Norwood guidelines. Of 35 women, 16 had grade I, 10 had grade II, and 1 had grade III Ludwig classification. In addition, 6 other women had Christmas tree baldness: 1 each of fronto-parietal and male pattern baldness. Several investigations including hormonal profile were inconclusive; however, hair pull test and trichogram may be helpful in understanding the sequence in AA in women. AA has infrequently been reported, particularly India and in Asia in general.

  9. Multiple arterial thromboses associated with anabolic androgenic steroids.

    Science.gov (United States)

    McCulloch, Neil Arthur; Abbas, Jonathan Raihan; Simms, Malcolm Harold

    2014-03-01

    The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.

  10. Plasma androgen concentrations in initial samples from spotted ...

    African Journals Online (AJOL)

    1990-01-31

    Jan 31, 1990 ... initial samples, the immobilization stress response and the response to exogenous GnRH administration, for ... the sex-specific differences in plasma androgens is confounded by other variables such as the reproductive.

  11. 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.

  12. 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.

  13. 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....

  14. 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

  15. 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...

  16. Hapalindole H Induces Apoptosis as an Inhibitor of NF-ĸB and Affects the Intrinsic Mitochondrial Pathway in PC-3 Androgen-insensitive Prostate Cancer Cells.

    Science.gov (United States)

    Acuña, Ulyana Muñoz; Mo, Shunyan; Zi, Jiachen; Orjala, Jimmy; DE Blanco, Esperanza J Carcache

    2018-06-01

    Prostate cancer presents the highest incidence rates among all cancers in men. Hapalindole H (Hap H), isolated from Fischerella muscicola (UTEX strain number LB1829) as part of our natural product anticancer drug discovery program, was found to be significantly active against prostate cancer cells. In this study, Hap H was tested for nuclear factor-kappa B (NF-ĸB) inhibition and selective cytotoxic activity against different cancer cell lines. The apoptotic effect was assessed on PC-3 prostate cancer cells by fluorescence-activated cell sorting analysis. The underlying mechanism that induced apoptosis was studied and the effect of Hap H on mitochondria was evaluated and characterized using western blot and flow cytometric analysis. Hap H was identified as a potent NF-ĸB inhibitor (0.76 μM) with selective cytotoxicity against the PC-3 prostate cancer cell line (0.02 μM). The apoptotic effect was studied on PC-3 cells. The results showed that treatment of PC-3 cells with Hap H reduced the formation of NAD(P)H, suggesting that the function of the outer mitochondrial membrane was negatively affected. Thus, the mitochondrial transmembrane potential was assessed in Hap H treated cells. The results showed that the outer mitochondrial membrane was disrupted as an increased amount of JC-1 monomers were detected in treated cells (78.3%) when compared to untreated cells (10.1%), also suggesting that a large number of treated cells went into an apoptotic state. Hap H was found to have potent NF-ĸB p65-inhibitory activity and induced apoptosis through the intrinsic mitochondrial pathway in hormone-independent PC-3 prostate cancer cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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 ...

  3. 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.

  4. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  5. 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.

  6. Pseudohypopituitary syndromes.

    Science.gov (United States)

    Heinze, E; Holl, R W

    1992-07-01

    In a child with short stature, the finding of normal or elevated GH levels in the presence of low concentrations of IGF-I raises the following possibilities. (1) A modification of the GH molecule, which is still detected by RIA, but inactive biologically. Therefore, an RRA or bioassay for hGH should result in considerably lower GH measurements compared with RIA determinations in the same sample. As both bioassays as well as RRAs are not widely available and are hampered by several difficulties, few children with this presumptive diagnosis have been described. So far, it has not been possible to define a specific molecular defect in one of these patients. (2) Abnormalities of the GH receptor or postreceptor mechanisms lead to a GH insensitivity syndrome. Laron-type dwarfism is usually due to a deletion in the gene for hepatic GH receptors: the serum binding protein for GH is absent. In three additional populations, the Pygmies of Zaire, the little women of Loja in Ecuador and the Mountain Ok people in Papua New Guinea, alterations of GH receptor function have been described. Finally, some reports describe patients with normal or elevated serum levels of both growth hormone and IGF-I in whom resistance to IGF has been implied in the pathogenesis of small stature.

  7. 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.

  8. 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...

  9. Hematopoiesis-activating effects of androgen (fluoxymesterone)

    International Nuclear Information System (INIS)

    Shirakura, Takuo; Inoue, Tatsu; Maekawa, Tadashi.

    1978-01-01

    Hematopoiesis-activating effect of fluoxymesterone (FMT) (androgen preparation) on hematopoietic hematoblast was evaluated. The results were as follows. (1) To C 3 H/He strain male mice, 2 mg/day of FMT was injected into each femoral muscle alternatively. On the 5th day of the first injection, radioactive iron was injected intraperitoneally; after 48 hrs, blood was collected for examining the incorporation rate of 59 Fe. The results showed significant increase. (2) After 4 mg of FMT was injected once into the femoral muscle, spleen colony-forming cells (CFU-S) of the mouse femur were examined. Calculation of either of surface colonies and microscopic colonies showed absolute increase of the number of CFU-S in the femoral marrow. The microscopic colonies were classified into three colony types of erythrocytes, granulocytes, and megakaryocytes on the basis of histology of the cellular component; and changes were evaluated in each type of the colonies. This evaluation clarified that an increase in colonies which appeared 24 hrs after the injection of the hormon was due to an increase in the erythrocyte and megakaryocyte colonies and that which appeared 48 hrs after the injection was due to an increase in granulocyte colonies. (Ueda, J.)

  10. Mass spectrometry of selective androgen receptor modulators.

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2008-07-01

    Nonsteroidal selective androgen receptor modulators (SARMs) are an emerging class of drugs for treatment of various diseases including osteoporosis and muscle wasting as well as the correction of age-related functional decline such as muscle strength and power. Several SARMs, which have advanced to preclinical and clinical trials, are composed of diverse chemical structures including arylpropionamide-, bicyclic hydantoin-, quinoline-, and tetrahydroquinoline-derived nuclei. Since January 2008, SARMs have been categorized as anabolic agents and prohibited by the World Anti-Doping Agency (WADA). Suitable detection methods for these low-molecular weight drugs were based on mass spectrometric approaches, which necessitated the elucidation of dissociation pathways in order to characterize and identify the target analytes in doping control samples as well as potential metabolic products and synthetic analogs. Fragmentation patterns of representatives of each category of SARMs after electrospray ionization (ESI) and collision-induced dissociation (CID) as well as electron ionization (EI) are summarized. The complexity and structural heterogeneity of these drugs is a daunting challenge for detection methods. Copyright 2008 John Wiley & Sons, Ltd.

  11. Predictors of future anabolic androgenic steroid use.

    Science.gov (United States)

    Wichstrøm, Lars

    2006-09-01

    To prospectively study the stability of anabolic androgenic steroid (AAS) use and predictors of AAS use, and to investigate whether AAS use alters the risk of later emotional and behavioral problems. Survey of a national sample of Norwegian high school students (age 15-19) in 1994 followed up in 1999 (N = 2924). Measures of frequent alcohol intoxication (50+ times per 12 months), cannabis use (12 months), hard drug use (12 months), being offered cannabis, eating problems, conduct problems, sexual debut before age 15, BMI, involvement in power sports, perceived physical appearance, and satisfaction with body parts were obtained. Life-time prevalence of AAS use were 1.9 and 0.8% in the follow-up period. Multivariate logistic regression revealed that future AAS use was predicted by young age, male gender, previous AAS use, involvement in power sports, and frequent alcohol intoxication. AAS use did not predict future emotional or behavioral problems other than reducing the risk of future frequent alcohol intoxication. Frequent alcohol intoxication and involvement in power sports appear to predict future AAS use. At the population level there was little stability in individual AAS use from adolescence to early adulthood. No detrimental effects of AAS use could be detected in this study, but low statistical power limits this conclusion.

  12. Review of Androgenic Anabolic Steroid Use

    Energy Technology Data Exchange (ETDEWEB)

    T. Borges; G. Eisele; C. Byrd

    2001-07-31

    An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).

  13. Impact of a program to diminish gender insensitivity and sexual harassment at a medical school.

    Science.gov (United States)

    Jacobs, C D; Bergen, M R; Korn, D

    2000-05-01

    To measure the effect of an intervention to reduce gender insensitivity and sexual harassment at one medical school. Stanford University School of Medicine undertook a multifaceted program to educate faculty and students regarding gender issues and to diminish sexual harassment. The authors developed a survey instrument to assess the faculty's perceptions regarding environment (five scales) and incidences of sexual harassment. Faculty were surveyed twice during the interventions (1994 and 1995). Between the two years, the authors measured significant improvements in mean ratings for positive climate (p = .004) and cohesion (p = .006) and decreases in the faculty's perceptions of sexual harassment (p = 0006), gender insensitivity (p = .001), and gender discrimination (p = .004). The faculty also reported fewer observations of harassing behavior during the study period. An intervention program to diminish gender insensitivity and sexual harassment can measurably improve a medical school's environment.

  14. 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.

  15. Specific interaction of radioactive anti-androgen TSAA-291 with androgen receptor in rat prostates

    International Nuclear Information System (INIS)

    Sudo, K.; Yoshida, K.; Nakayama, R.

    1982-01-01

    A steroidal anti-androgen TSSA-291 (16β-ethyl-17β-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (Kdsub(d) = 5.0 x 10 -9 M) and in a saturable manner. The number of binding sites was comparable to that for 5α-dihydrotestosterone (5α-DHT). [ 3 H]TSAA-291 binding was effectively displaced by unlabelled 5α-DHT, 19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficient of the [ 3 H]-TSAA-291-macromolecule complex was 3-4.5 S. However, when the unlabelled cytosol was fractionated by glycerol density-gradient centrifugation before the binding of [ 3 H]TSAA-291 was examined, specific binding of [ 3 H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [ 3 H]TSAA-291-macromolecules comples to prostatic nuclei and DNA-cellulose was considerably less than binding by the [ 3 H]5α-DHT-macromolecule complex. Instability of the TSAA-291 binding coponent on heat treatment before and after complex formation was also revealed and the results are discussed in terms of the anti-androgenic activity of TSAA-291. (author)

  16. The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer

    NARCIS (Netherlands)

    Jongen, V. H. W. M.; Sluijmer, A. V.; Heineman, M. J.

    2002-01-01

    Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen

  17. Interaction Between a Novel p21 Activated Kinase (PAK6) and Androgen Receptor in Prostate Cancer

    National Research Council Canada - National Science Library

    Sun, Zijie

    2005-01-01

    The effects of androgens are mediated by the androgen receptor (AR), which plays a critical role in inducing normal differentiation of tissues of the reproductive organs and in the development and progression of prostate cancer...

  18. 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...

  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. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigsby, James

    2004-01-01

    .... Our major hypothesis is the patients undergoing androgen deprivation therapy will experience impairments in those cognitive abilities reported in the research literature to be related to androgen levels (e.g...

  1. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigaby, James

    2003-01-01

    .... Our major hypothesis is that patients undergoing androgen deprivation therapy will experience impairments in those cognitive abilities reported in the research literature to be related to androgen levels (e.g...

  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. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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...

  10. 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...

  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. Beals Syndrome

    Science.gov (United States)

    ... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of the ... bone) and aortic enlargement problems as people with Marfan syndrome, and treatments for these problems are the same. ...

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Switching an O2 sensitive glucose oxidase bioelectrode into an almost insensitive one by cofactor redesign.

    Science.gov (United States)

    Tremey, Emilie; Suraniti, Emmanuel; Courjean, Olivier; Gounel, Sébastien; Stines-Chaumeil, Claire; Louerat, Frédéric; Mano, Nicolas

    2014-06-04

    In the 5-8 mM glucose concentration range, of particular interest for diabetes management, glucose oxidase bioelectrodes are O2 dependent, which decrease their efficiencies. By replacing the natural cofactor of glucose oxidase, we succeeded in turning an O2 sensitive bioelectrode into an almost insensitive one.

  4. Can Parents' Involvement in Children's Education Offset the Effects of Early Insensitivity on Academic Functioning?

    Science.gov (United States)

    Monti, Jennifer D.; Pomerantz, Eva M.; Roisman, Glenn I.

    2014-01-01

    Data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,312) were analyzed to examine whether the adverse effects of early insensitive parenting on children's academic functioning can be offset by parents' later involvement in children's education. Observations of mothers' early…

  5. A Chroma-based Tempo-insensitive Distance Measure for Cover Song Identification

    DEFF Research Database (Denmark)

    Jensen, Jesper Højvang; Ellis, Dan P. W.; Christensen, Mads Græsbøll

    In the context of music, a cover version is a remake of a song, often with significant stylistic variation. In this paper we describe a distance measure between sampled audio files that is designed to be insensitive to instrumentation, time shift, temporal scaling and transpositions. The algorithm...

  6. DEFECTS IN INSULIN-SECRETION IN NIDDM - B-CELL GLUCOSE INSENSITIVITY OR GLUCOSE TOXICITY

    NARCIS (Netherlands)

    VANHAEFTEN, TW

    In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is ''blind'' for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This

  7. Using metrics for proof rules for recursively defined delay-insensitive specifications

    NARCIS (Netherlands)

    Mallon, WC; Udding, JT

    1997-01-01

    An advantage of algebraic specifications of delay insensitive asynchronous processes over most other formalisms is that it allows the recursive definition of processes, and correctness proofs of an implementation through fixpoint induction. On the other hand, proofs by fixpoint induction are

  8. Progressing Insensitive Munitions: Benefits and Techniques for Proactively Addressing Environmental Regulations

    Science.gov (United States)

    2012-05-01

    X Worm Tubifex tubifex X X X Black worm Lumbriculus X Asiatic clam Corbicula fluminea X Estuarine/marine water column Mysid shrimp Americamysis...Objective: Characterize traditional and insensitive munitions (IMs) impacts on amphibian larvae to manage a candidate for T&E status that inhabit

  9. 320 Gb/s Nyquist OTDM received by polarization-insensitive time-domain OFT

    DEFF Research Database (Denmark)

    Hu, Hao; Kong, Deming; Palushani, Evarist

    2014-01-01

    We have demonstrated the generation of a 320 Gb/s Nyquist-OTDM signal by rectangular filtering on an RZ-OTDM signal with the filter bandwidth (320 GHz) equal to the baud rate (320 Gbaud) and the reception of such a Nyquist-OTDM signal using polarization-insensitive time-domain optical Fourier tra...

  10. 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.

  11. 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

  12. Loss of peroxisomes causes oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity to detect cancer cells

    NARCIS (Netherlands)

    Frederiks, Wilma M.; Vreeling-Sindelárová, Heleen; van Noorden, Cornelis J. F.

    2007-01-01

    Oxygen insensitivity of carcinoma cells and oxygen sensitivity of non-cancer cells in the histochemical assay of glucose-6-phosphate dehydrogenase (G6PD) enables detection of carcinoma cells in unfixed cell smears or cryostat sections of biopsies. The metabolic background of oxygen insensitivity is

  13. Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

    Science.gov (United States)

    Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong; Liu, Wei

    2017-03-01

    Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. Copyright © 2017 by the Endocrine Society

  14. 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.

  15. 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.

  16. 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

  17. Role of Hsp90 in Androgen-Refractory Prostate Cancer

    Science.gov (United States)

    2010-03-01

    designed siRNA sequence using Intergrated DNA Technologies RNAi online software tool (IDT, Coralville, IA). The sequence of siRNA specific for...proliferation and production of prostate-specific antigen in androgen-sensitive pros- tatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136

  18. Prevalence and awareness of anabolic androgenic steroid use ...

    African Journals Online (AJOL)

    Purpose: To examine the prevalence and awareness of anabolic-androgenic steroid (AAS) use among male bodybuilders visiting gyms in Jazan region, Saudi Arabia. Methods: A cross-sectional survey was conducted among 500 male bodybuilders visiting gyms in the Jazan region of Saudi Arabia. Information on ...

  19. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    Science.gov (United States)

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  20. Psychological and Behavioral Effects of Anabolic-Androgenic Steroids.

    Science.gov (United States)

    Bahrke, Michael S.

    This review of the literature on the psychological and behavioral effects of anabolic-androgenic steroids (AS) first looks at aspects of the history and prevalence of AS use in competitive sports. Research suggests that one-quarter to one-half million adolescents in the United States have used, or are currently using AS. Some effects of androgens…

  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. 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.

  3. Procoagulant State in Current and Former Anabolic Androgenic Steroid Abusers

    DEFF Research Database (Denmark)

    Chang, Simon; Rasmussen, Jon J; Frandsen, Mikkel N

    2018-01-01

    BACKGROUND:  Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS:  Men 18 to 50 years of age were included...

  4. Expression of androgen and estrogen receptors in the testicular ...

    African Journals Online (AJOL)

    enoh

    2012-04-10

    Apr 10, 2012 ... 66: 1161-1168. Oliveira CA, Mahecha GA, Carnes K, Prins GS, Saunders PT, Franca. LR, Hess RA (2004). Differential hormonal regulation of estrogen receptors ERα and ER and androgen receptor expression in rat efferent ductules. Reproduction, 128(1): 73-86. O'Shaughnessy PJ, Johnston H, Willerton L ...

  5. Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Hnida, Christina; Larsen, John Christian

    2000-01-01

    Nine structurally different polycyclic aromatic hydrocarbons (PAHs) were tested for their ability to either agonize or antagonize the human androgen receptor (hAR) in a sensitive reporter gene assay based on CHO cells transiently cotransfected with a hAR vector and an MMTV-LUC vector. Benz...

  6. 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.

  7. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2010-01-01

    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  8. Reduced fetal androgen exposure compromises Leydig cell function in adulthood

    NARCIS (Netherlands)

    Teerds, K.J.; Keijer, J.

    2015-01-01

    Disruption of normal fetal development can influence functioning of organs and cells in adulthood. Circumstantial evidence suggests that subtle reductions in fetal androgen production may be the cause of adult male reproductive disorders due to reduced testosterone production. The mechanisms through

  9. Unique Approaches to Androgen Effects on Prostate Cancer

    National Research Council Canada - National Science Library

    Rosner, W; Kahn, S. M

    2007-01-01

    Sex hormone-binding globulin (SHBG) is a plasma protein that binds andrngens and it acts as a transducer of androgen signaling at the plasma membrane of prostate cancer cells The human prostate cancer cell line LNCaP in addition...

  10. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... Cushing syndrome . Prednisone, dexamethasone, and prednisolone ...

  11. LEOPARD syndrome

    Science.gov (United States)

    Multiple lentigines syndrome; Noonan syndrome with multiple lentigines ... Genetics Home Reference -- ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines National Organization for Rare Disorders -- ...

  12. Neural androgen receptors modulate gene expression and social recognition but not social investigation

    Directory of Open Access Journals (Sweden)

    Sara A Karlsson

    2016-03-01

    Full Text Available The role of sex and androgen receptors (ARs for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR-independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest towards male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDel males recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esr1, Cyp19a1, Ucn3, Crh and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation towards both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William’s syndrome.

  13. Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2014-07-01

    In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5α-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. © 2014 Society for Endocrinology.

  14. 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...

  15. 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

  16. 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

  17. 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.

  18. 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 ...

  19. 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

  20. 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.

  1. Polycystic Ovary Syndrome

    Science.gov (United States)

    ... suggests that certain genes might be linked to PCOS. Excess androgen. The ovaries produce abnormally high levels of androgen, resulting in hirsutism and acne. Complications Complications of PCOS can include: Infertility Gestational diabetes or pregnancy-induced ...

  2. Tolerance of photoperiod insensitive mutant of Sesbania rostrata to salinity and pH

    International Nuclear Information System (INIS)

    Ramani, Saradha; Joshua, D.C.; Shaikh, M.S.; Athalye, V.V.

    1998-01-01

    The photoperiod insensitive mutant, TSR-1 of Sesbania rostrata was compared with the parent variety for its response to soil salinity and different levels of pH in hydroponics. The plant growth and stem nodulation were not significantly affected by salinity. However, salinity in soil without farmyard manure stimulated plant growth. Radiotracer studies showed that the translocation of Na to stem and leaves was much less compared to uptake in both parent and mutant. The growth of TSR-1 was comparable to or marginally better than that of the parent variety in the pH range of 3.5-8.0. Root nodulation was less with low pH. The nitrogen content was not adversely affected by pH, but it was reduced with 200 mM NaCl. This mutant in addition to being short-day insensitive, is tolerant to low to moderate salinity levels and pH like its parent. (author)

  3. Optimal Design of an Achromatic Angle-Insensitive Phase Retarder Used in MWIR Imaging Polarimetry

    International Nuclear Information System (INIS)

    Guo-Guo, Kang; Qiao-Feng, Tan; Guo-Fan, Jin

    2009-01-01

    Dielectric gratings with period in the range from λ/10 to λ/4 with λ being the illumination wavelength not only exclude higher order diffractions but also exhibit strong dispersion of effective indices which are proportional to the wavelength. Moreover, they are insensitive to the incident angle of the illumination wave. With these features, we can design a true zero-order achromatic and angle-insensitive phase retarder which can be used as the polarization state analyzer in middle wave infrared (MWIR) imaging polarimetry. A design method using effective medium theory is described, and the performance of the designed phase retarder is evaluated by rigorous coupled wave analysis theory. The calculation results demonstrate that the retardance deviates from 45° by < ±1.6° within a field of view ±10° over the MWIR bandwidth (3–5 μm). (fundamental areas of phenomenology (including applications))

  4. 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.

  5. A natural frameshift mutation in Campanula EIL2 correlates with ethylene insensitivity in flowers

    DEFF Research Database (Denmark)

    Jensen, Line; Hegelund, Josefine Nymark; Olsen, Andreas

    2016-01-01

    BACKGROUND: The phytohormone ethylene plays a central role in development and senescence of climacteric flowers. In ornamental plant production, ethylene sensitive plants are usually protected against negative effects of ethylene by application of chemical inhibitors. In Campanula, flowers...... are sensitive to even minute concentrations of ethylene. RESULTS: Monitoring flower longevity in three Campanula species revealed C. portenschlagiana (Cp) as ethylene sensitive, C. formanekiana (Cf) with intermediate sensitivity and C. medium (Cm) as ethylene insensitive. We identified key elements in ethylene...... signal transduction, specifically in Ethylene Response Sensor 2 (ERS2), Constitutive Triple Response 1 (CTR1) and Ethylene Insensitive 3- Like 1 and 2 (EIL1 and EIL2) homologous. Transcripts of ERS2, CTR1 and EIL1 were constitutively expressed in all species both throughout flower development...

  6. 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

  7. The molecular basis of acid insensitivity in the African naked mole-rat.

    Science.gov (United States)

    Smith, Ewan St John; Omerbašić, Damir; Lechner, Stefan G; Anirudhan, Gireesh; Lapatsina, Liudmila; Lewin, Gary R

    2011-12-16

    Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.

  8. Wafer defect detection by a polarization-insensitive external differential interference contrast module.

    Science.gov (United States)

    Nativ, Amit; Feldman, Haim; Shaked, Natan T

    2018-05-01

    We present a system that is based on a new external, polarization-insensitive differential interference contrast (DIC) module specifically adapted for detecting defects in semiconductor wafers. We obtained defect signal enhancement relative to the surrounding wafer pattern when compared with bright-field imaging. The new DIC module proposed is based on a shearing interferometer that connects externally at the output port of an optical microscope and enables imaging thin samples, such as wafer defects. This module does not require polarization optics (such as Wollaston or Nomarski prisms) and is insensitive to polarization, unlike traditional DIC techniques. In addition, it provides full control of the DIC shear and orientation, which allows obtaining a differential phase image directly on the camera (with no further digital processing) while enhancing defect detection capabilities, even if the size of the defect is smaller than the resolution limit. Our technique has the potential of future integration into semiconductor production lines.

  9. Polarization insensitive metamaterial absorber based on E-shaped all-dielectric structure

    Directory of Open Access Journals (Sweden)

    Liyang Li

    2015-03-01

    Full Text Available In this paper, we designed a metamaterial absorber performed in microwave frequency band. This absorber is composed of E-shaped dielectrics which are arranged along different directions. The E-shaped all-dielectric structure is made of microwave ceramics with high permittivity and low loss. Within about 1 GHz frequency band, more than 86% absorption efficiency was observed for this metamaterial absorber. This absorber is polarization insensitive and is stable for incident angles. It is figured out that the polarization insensitive absorption is caused by the nearly located varied resonant modes which are excited by the E-shaped all-dielectric resonators with the same size but in the different direction. The E-shaped dielectric absorber contains intensive resonant points. Our research work paves a way for designing all-dielectric absorber.

  10. Dye and pigment-free structural colors and angle-insensitive spectrum filters

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lingjie Jay; Hollowell, Andrew E.; Wu, Yi-Kuei

    2017-01-17

    Optical spectrum filtering devices displaying minimal angle dependence or angle insensitivity are provided. The filter comprises a localized plasmonic nanoresonator assembly having a metal material layer defining at least one nanogroove and a dielectric material disposed adjacent to the metal material layer. The dielectric material is disposed within the nanogroove(s). The localized plasmonic nanoresonator assembly is configured to funnel and absorb a portion of an electromagnetic spectrum in the at least one nanogroove via localized plasmonic resonance to generate a filtered output having a predetermined range of wavelengths that displays angle insensitivity. Thus, flexible, high efficiency angle independent color filters having very small diffraction limits are provided that are particularly suitable for use as pixels for various display devices or for use in anti-counterfeiting and cryptography applications. The structures can also be used for colored print applications and the elements can be rendered as pigment-like particles.

  11. Polarization Insensitivity in Double-Split Ring and Triple-Split Ring Terahertz Resonators

    International Nuclear Information System (INIS)

    Wu Qian-Nan; Lan Feng; Tang Xiao-Pin; Yang Zi-Qiang

    2015-01-01

    A modified double-split ring resonator and a modified triple-split ring resonator, which offer polarization-insensitive performance, are investigated, designed and fabricated. By displacing the two gaps of the conventional double-split ring resonator away from the center, the second resonant frequency for the 0° polarized wave and the resonant frequency for the 90° polarized wave become increasingly close to each other until they are finally identical. Theoretical and experimental results show that the modified double-split ring resonator and the modified triple-split ring resonator are insensitive to different polarized waves and show strong resonant frequency dips near 433 and 444 GHz, respectively. The results of this work suggest new opportunities for the investigation and design of polarization-dependent terahertz devices based on split ring resonators. (paper)

  12. Observing Local Realism Violations with a Combination of Sensitive and Insensitive Detectors

    International Nuclear Information System (INIS)

    Yurke, B.; Stoler, D.

    1997-01-01

    Several systems are exhibited in which the establishment of local realism violation is achieved even when some of the detectors employed are insensitive. The insensitive detectors are homodyne detectors whose task is to determine if the amplitude of a coherent state is α or -α . This determination can be achieved with low quantum efficiency detectors when |α| is large. The other detectors employed determine whether there is an even number or an odd number of photons in a state. These detectors are sensitive since they are required to resolve the difference of one photon. For the examples given, the local realism violation is not diminished as |α| is increased. copyright 1997 The American Physical Society

  13. 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.

  14. Fanconi syndrome

    Science.gov (United States)

    De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

  15. Duane Syndrome

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Duane Syndrome En Español Read in Chinese What is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), ...

  16. Humidity insensitive step-index polymer optical fibre Bragg grating sensors

    DEFF Research Database (Denmark)

    Woyessa, Getinet; Fasano, Andrea; Stefani, Alessio

    2015-01-01

    We have fabricated and characterised a humidity insensitive step index(SI) polymer optical fibre(POF) Bragg grating sensors. The fibre was made based on the injection molding technique, which is an efficient method for fast, flexible and cost effective preparation of the fibre preform. The fabric...... poly-methyl-methacrylate (PMMA) based SIPOFs. The fibre has a minimum loss of similar to 6dB/m at 770nm....

  17. The arcuate artery in renal transplants: An insensitive indicator of rejection

    International Nuclear Information System (INIS)

    McIntire, J.N.; Angtuaco, T.L.; Boyd, C.; Flanigan, W.J.

    1987-01-01

    The authors performed 65 duplex US examinations in 28 patients within 2 years of transplantation. During this time 15 episodes of rejection were diagnosed by US and confirmed clinically. Of the remaining 50 examinations, 14 showed negligible or absent diastolic flow (suggesting rejection) in the arcuate arteries with normal diastolic flow in the main renal, segmental, and interlobar branches. No other criteria for rejection were present in these patients. It is concluded that the arcuate artery is an insensitive indicator of transplant rejection

  18. Eksplozivne materije za neosetljiva ubojna sredstva / Explosive substances for insensitive munitions

    Directory of Open Access Journals (Sweden)

    Radun Jeremić

    2005-03-01

    Full Text Available U skladu sa sve strožim zahtevima za očuvanje životne sredine i većom bezbednošću, tendencije u razvoju suvremenih ubojnih sredstava (UbS, pored povećanja pouzdanosti i efikasnosti, usmerene su i na povećanje sigurnosti pri njihovoj proizvodnji, skladištenju, manipulaciji i upotrebi. Na taj način dobijena je nova kategorija UbS, tzv. neosetljiva UbS, kod kojih je verovatnoća neželjenog aktiviranja pod dejstvom spoljnih impulsa svedena na minimum. Suština rešavanja ovog problema je primena eksplozivnih materija koje su mnogo manje osetljive na spoljne uticaje u odnosu na standardne. Osnovni zahtev koji se pri tome postavlja je da taktičko-tehničke karakteristike ostanu na nivou ili budu bolje u odnosu na postojeća UbS. U radu je ukratko objašnjen koncept razvoja neosetljivih UbS i dat pregled najznačajnijih rezultata istraživanja u oblasti eksplozivnih materija koje zadovoljavaju zahteve za primenu u neosetljivim UbS. / According to severe environment protection and safety requirements, tendencies in development of modern munitions, besides of increasing reliability and efficiency, are directed to decreasing of danger during their processing, storing, handling and operating. In that manner the new category of munitions has been obtained, named insensitive munitions, with a minimum probability of unplanned activating. The best method for solving this problem is using of explosive substances that are more insensitive according to standard ones. The main requirement is the tactical and technical characteristics stay at the level or to be better according to the existing munitions. In this paper the developing concept of insensitive munitions is shortly explained and presented a review of most important research results of explosive materials that fulfill requirements for applying in insensitive munitions.

  19. Compact temperature-insensitive modulator based on a silicon microring assistant Mach—Zehnder interferometer

    International Nuclear Information System (INIS)

    Zhang Xue-Jian; Feng Xue; Zhang Deng-Ke; Huang Yi-Dong

    2012-01-01

    On the silicon-on-insulator platform, an ultra compact temperature-insensitive modulator based on a cascaded microring assistant Mach—Zehnder interferometer is proposed and demonstrated with numerical simulation. According to the calculated results, the tolerated variation of ambient temperature can be as high as 134 °C while the footprint of such a silicon modulator is only 340 μm 2 . (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  20. Laser ignitibility of insensitive secondary explosive 1,1-diamino-2,2-dinitroethene (FOX-7)

    International Nuclear Information System (INIS)

    Fang, Xiao; McLuckie, Warren G

    2015-01-01

    Highlights: • Carbon black (CB) is an efficient optical sensitizer compatible with 1,1-diamino-2,2-dinitroethene (FOX-7). • A CB doped insensitive explosive FOX-7 can be ignited by a low-power diode laser. • Laser ignitibility of the optically sensitized FOX-7 is mainly affected by laser power among the other parameters. • Inhomogeneities in the explosive affect laser ignition reliability. - Abstract: An experimental investigation into laser ignitibility of insensitive secondary explosives, 1,1-diamino-2,2-dinitroethene (FOX-7) has been carried out, using a diode laser of continuous wave at the laser wavelength of 974 nm. The direct optical ignition of an insensitive explosive will add more safety features to insensitive munitions (IM) or explosive devices. In this study, effects of laser parameters on the ignitibility were analysed in terms of laser ignition threshold, the times to initiate the ignition and full combustion, and burning sustainability. The results have shown that carbon black (CB) as an optical sensitizer is compatible with FOX-7, and significantly enhances laser ignitibility of the explosive when a small amount of CB is uniformly doped in FOX-7. The delay times for ignition and subsequent development of sustainable burning of the material are mainly determined by ignition laser power, although the other laser parameters have effects. The minimum laser power required to ignite the optically sensitized FOX-7 was found below 10 W and a fast ignition was initiated in as short as 70 μs by a laser power of 40 W. Also the effect of the mixture uniformity of FOX-7/CB on laser ignition performance was evaluated in this study

  1. Congenital insensitivity to pain and anhidrosis: A case report from South India

    Directory of Open Access Journals (Sweden)

    Carounanidy Udayashankar

    2012-01-01

    Full Text Available Congenital insensitivity to pain with anhidrosis, also known as hereditary sensory and autonomic neuropathy type IV, is an autosomal recessive disorder characterized by the congenital lack of pain sensation, inability to sweat, episodes of recurrent hyperpyrexia, mental retardation, and self-mutilating behavior. It is an extremely rare disorder with only a handful of reports from India. A five- year- old boy, born to second-degree consanguineous parents after uneventful antenatal period, presented to us with history of recurrent unexplained fever, recurrent ulcers in the lower limbs, insensitivity to painful stimuli (like injections, vaccination and self-mutilating behavior from early childhood. Cutaneous examination showed multiple ulcers, loss of teeth, loss of tip of the tongue (due to biting, scarring of finger tips, xerosis and lichenification. Sensory examination showed complete loss of pain and temperature sensations, but fine touch and vibration were preserved. Deep tendon reflexes were normal. Evaluation for Hansen′s disease was non-contributory. An intradermal injection of histamine did not show any flare response. Based on clinical as well as compatible histological features a diagnosis of congenital insensitivity to pain with anhidrosis was made. The ulcers were treated with appropriate antibiotics and daily dressings. The parents were counseled about appropriate care of the child.

  2. Formulation development and characterization of cellulose acetate nitrate based propellants for improved insensitive munitions properties

    Directory of Open Access Journals (Sweden)

    Thelma Manning

    2014-06-01

    Full Text Available Cellulose acetate nitrate (CAN was used as an insensitive energetic binder to improve the insensitive munitions (IM properties of gun propellants to replace the M1 propellant used in 105 mm artillery charges. CAN contains the energetic nitro groups found in nitrocellulose (NC, but also acetyl functionalities, which lowered the polymer's sensitivity to heat and shock, and therefore improved its IM properties relative to NC. The formulation, development and small-scale characterization testing of several CAN-based propellants were done. The formulations, using insensitive energetic solid fillers and high-nitrogen modifiers in place of nitramine were completed. The small scale characterization testing, such as closed bomb testing, small scale sensitivity, thermal stability, and chemical compatibility were done. The mechanical response of the propellants under high-rate uni-axial compression at, hot, cold, and ambient temperatures were also completed. Critical diameter testing, hot fragment conductive ignition (HFCI tests were done to evaluate the propellants' responses to thermal and shock stimuli. Utilizing the propellant chemical composition, theoretical predictions of erosivity were completed. All the small scale test results were utilized to down-select the promising CAN based formulations for large scale demonstration testing such as the ballistic performance and fragment impact testing in the 105 mm M67 artillery charge configurations. The test results completed in the small and large scale testing are discussed.

  3. Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

    Science.gov (United States)

    Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

    2010-02-01

    Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.

  4. Calcitonin gene-related peptide alters the firing rates of hypothalamic temperature sensitive and insensitive neurons

    Directory of Open Access Journals (Sweden)

    Grimm Eleanor R

    2008-07-01

    Full Text Available Abstract Background Transient hyperthermic shifts in body temperature have been linked to the endogenous hormone calcitonin gene-related peptide (CGRP, which can increase sympathetic activation and metabolic heat production. Recent studies have demonstrated that these centrally mediated responses may result from CGRP dependent changes in the activity of thermoregulatory neurons in the preoptic and anterior regions of the hypothalamus (POAH. Results Using a tissue slice preparation, we recorded the single-unit activity of POAH neurons from the adult male rat, in response to temperature and CGRP (10 μM. Based on the slope of firing rate as a function of temperature, neurons were classified as either warm sensitive or temperature insensitive. All warm sensitive neurons responded to CGRP with a significant decrease in firing rate. While CGRP did not alter the firing rates of some temperature insensitive neurons, responsive neurons showed an increase in firing rate. Conclusion With respect to current models of thermoregulatory control, these CGRP dependent changes in firing rate would result in hyperthermia. This suggests that both warm sensitive and temperature insensitive neurons in the POAH may play a role in producing this hyperthermic shift in temperature.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  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. 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.

  11. 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

  12. Incorporating mesh-insensitive structural stress into the fatigue assessment procedure of common structural rules for bulk carriers

    Directory of Open Access Journals (Sweden)

    Seong-Min Kim

    2015-01-01

    Full Text Available This study introduces a fatigue assessment procedure using mesh-insensitive structural stress method based on the Common Structural Rules for Bulk Carriers by considering important factors, such as mean stress and thickness effects. The fatigue assessment result of mesh-insensitive structural stress method have been compared with CSR procedure based on equivalent notch stress at major hot spot points in the area near the ballast hold for a 180 K bulk carrier. The possibility of implementing mesh-insensitive structural stress method in the fatigue assessment procedure for ship structures is discussed.

  13. 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

  14. 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

  15. 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...

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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