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Sample records for androgen insensitivity syndrome

  1. 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

  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. Three siblings with complete androgen insensitivity syndrome ...

    African Journals Online (AJOL)

    A diagnosis of complete androgen insensitivity syndrome was made, based on this clinical picture and laboratory findings. Two of her younger siblings were subsequently also diagnosed with this condition. She underwent an orchidectomy and is currently on female hormone replacement therapy. At the time of writing up ...

  4. 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.

  5. Genetics Home Reference: androgen insensitivity syndrome

    Science.gov (United States)

    ... allow cells to respond to androgens, which are hormones (such as testosterone ) that direct male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating ...

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis

    OpenAIRE

    Bhangoo, Amrit; Paris, Francoise; Philibert, Pascal; Audran, Francoise; Ten, Svetlana; Sultan, Charles

    2010-01-01

    Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-α reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-...

  13. 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

  14. Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology.

    Science.gov (United States)

    Kaprova-Pleskacova, Jana; Stoop, Hans; Brüggenwirth, Hennie; Cools, Martine; Wolffenbuttel, Katja P; Drop, Stenvert L S; Snajderova, Marta; Lebl, Jan; Oosterhuis, J Wolter; Looijenga, Leendert H J

    2014-05-01

    Patients with complete androgen insensitivity syndrome are at an increased risk for the development of gonadal germ cell cancer. Residual androgen receptor (AR) activity and abnormal gonadal location may influence the survival of atypical germ cells and the development of other histopathological features. To assess this, we evaluated 37 gonads from 19 patients with complete androgen insensitivity (ranging in age from 3 months to 18 years). Histological abnormalities were examined using hematoxylin and eosin-stained sections and sections stained for POU5F1 and KITLG, markers of early changes in germ cells at risk for malignant transformation. Hamartomatous nodules (HNs), Leydig cell hyperplasia (LCH), decreased germ cells, tubular atrophy and stromal fibrosis were more pronounced as age increased (Peffect of inguinal versus abdominal position of the gonads was difficult to assess because inguinal gonads were present primarily in the youngest individuals. In conclusion, many histological changes occur increasingly with age. Expected residual AR activity contributes to better survival of the general germ cell population in (post)pubertal age; however, it did not seem to have an important role in the survival of the germ cells at risk for malignant transformation (defined by POU5F1 positivity and KITLG overexpression) in complete androgen insensitivity. Comparison of the high percentage of patients in our study that were carrying germ cells with delayed maturation or pre-intratubular germ cell neoplasia with previously reported cumulative risk of tumor development in adult patients indicates that not all such precursor lesions in complete androgen insensitivity will progress to invasive germ cell cancer.

  15. 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.

  16. Bilateral Sertoli Cell Tumors in a Patient with Androgen Insensitivity Syndrome

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    Roberta Fonseca de Souza

    2017-01-01

    Full Text Available Androgen insensitivity syndrome is the most common cause of male pseudohermaphroditism and the third most common cause of primary amenorrhea. This genetic alteration is a consequence of inherited defects on the X chromosome causing total or partial damage to the intrauterine virilization process due to functional abnormalities in the androgen receptors. The present report describes a 22-year-old patient with a female phenotype and a 46, XY karyotype, presenting with bilateral inguinal tumors. The tumors were surgically removed at the Santa Casa de Misericórdia Hospital in Vitória, Espírito Santo, Brazil. Pathology revealed bilateral testicles with Sertoli cell tumors. According to the international literature, prophylactic gonadectomy following puberty is recommended due to the progressive risk of neoplastic transformation in the residual gonads.

  17. 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.

  18. Genetic diagnosis and genetic counseling for androgen-insensitivity syndrome: a report of three cases.

    Science.gov (United States)

    Yamaguchi, Masatoshi; Sameshima, Hiroshi; Ikenoue, Tyuyomu

    2014-03-01

    In order to verify androgen-insensitivity syndrome (AIS) for three individuals and their mothers, genetic diagnosis was performed after genetic counseling. Polymerase chain reaction analysis was used for each exon of the androgen receptor (AR Xq11-q12) gene. The amplified DNA fragments were detected by gel electrophoresis. The DNA fragments were sequenced and their sequences were compared with those in a database (The Androgen Receptor Gene Mutations Database World Wide Web Server). A missense mutation was identified in exon 7 in case 1, deletions of exons 1 and 2 were identified in case 2, and a nonsense mutation was identified in the triplet repeat region of exon 1 in case 3. The mothers of the patients were also verified to be carriers of the mutations. Genetic diagnosis is a very useful method for diagnosing AIS. However, genetic counseling, including emotional support for the mother, is an essential component of genetic diagnosis. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

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

    Directory of Open Access Journals (Sweden)

    Adam T Szafran

    2009-12-01

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

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

    Science.gov (United States)

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

    2003-04-01

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

  1. 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. [Vaginoplasty from peritoneal tube of Douglas' poutch for androgen insensitivity syndrome (two case reports)].

    Science.gov (United States)

    Ait Sakel, A; Asseban, M; Kallat, A; Elsayegh, H; Iken, A; Nouini, Y; Benslimane, L; Faik, M

    2014-06-01

    The androgen insensitivity syndrome (AIS) formerly known as testicular feminization is transmitted on a recessive X-linked. Its diagnosis is usually made at puberty if primary amenorrhea is present because the external genitalia are female. We report the case of two sisters aged 30 and 18 years, with testicular feminization syndrome discovered during the exploration of primary amenorrhea. Clinical examination found fairly well developed mammary glands, an hypertrophied clitoris, two formations in the labia majora corresponding to the testicles and agenesia of vagina. The uterus has not been seen on pelvic ultrasound and computed tomography scan of the pelvis. Cytogenetic analysis has objectified the chromosomal formula: 46 XY. We performed a vaginoplasty using peritoneum from the pouch of Douglas, a clitoroplasty and bilateral orchiectomy. The result was excellent. A neovagina with a depth of 6 cm was created. After 6 months of follow-up, the two sisters keep beautiful vaginal cavities with regular digital dilation. Peritoneum vaginoplasty is a simple and easy method for creating a neovagina with minimal complications. Its anatomical and functional results are satisfactory. Copyright © 2013. Published by Elsevier Masson SAS.

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

    Directory of Open Access Journals (Sweden)

    Felipe P. Andrade

    2012-10-01

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

  4. Complete androgen insensitivity syndrome associated with male gender identity or female precocious puberty in the same family.

    Science.gov (United States)

    Bermúdez de la Vega, José A; Fernández-Cancio, Mónica; Bernal, Susana; Audí, Laura

    2015-01-01

    In 4 complete androgen insensitivity syndrome (CAIS) members of one family, 2 presented extreme and unusual clinical features: male gender identity disorder (case 1) and female precocious central puberty (case 2). The AR gene carried the mutation c.1752C>G, p.Phe584Leu. Gender dysphoria in CAIS may be considered as a true transgender and has been described in 3 other cases. Central precocious puberty has only been described in 1 case; Müllerian ducts in case 2 permitted menarche. Despite the common CAIS phenotype, there was a familial disparity for gender identity adequacy and timing and type of puberty.

  5. Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

    Science.gov (United States)

    Hamann, Stephan; Stevens, Jennifer; Vick, Janice Hassett; Bryk, Kristina; Quigley, Charmian A; Berenbaum, Sheri A; Wallen, Kim

    2014-11-01

    Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Copyright © 2014 Elsevier Inc. All rights reserved.

  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. Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia.

    Science.gov (United States)

    Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm; Main, Katharina M; Duno, Morten; Juul, Anders

    2012-05-01

    To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome. Tertiary paediatric endocrine centre. Retrospective evaluation of 14 male patients with partial androgen insensitivity syndrome (PAIS) with verified androgen receptor (AR) mutations. The authors recorded phenotypic characteristics at birth and external masculinisation score (EMS), registered longitudinal growth, circulating levels of testosterone, estradiol, luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin-B and sex hormone binding globulin (SHBG), in addition to phenotype at postpubertal follow up. The EMS ranged from 5 to 12 in PAIS at birth. Six patients were born with hypospadias and all patients developed gynaecomastia in puberty. Eight of the patients received testosterone treatment. At follow-up penile size was impaired irrespective of EMS at birth, but responded to pubertal androgen therapy in some of the patients. Serum levels of testosterone, estradiol, SHBG and LH, but not FSH and inhibin B, were markedly elevated in puberty. Final height was 181.3 cm (165.7-190.5 cm) corresponding to an SD score of 0.7 (-2.1 to +2.1 SD, n=10). Gynaecomastia and impaired phallic growth are frequently observed in adults with PAIS, but may be ameliorated by androgen therapy. The authors suggest that male patients presenting with gynaecomastia in puberty, and elevated circulating levels of testosterone, estradiol and LH in puberty, but normal FSH, should be suspected of having PAIS and undergo genetic testing for AR mutations.

  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. 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...... pedigree segregating AIS, where the molecular analyses of the androgen receptor gene in the family provided evidences that a 25-bp deletion of the DNA-binding domain is causative of this equine syndrome....

  10. Diagnostic laparoscopy in a twelve year old girl with right iliac fossa pain: A life changing diagnosis of complete androgen insensitivity syndrome.

    Science.gov (United States)

    Meshkat, Babak; Matcovici, Melania; Buckley, Claire; Salama, Muhammad; Perthiani, Haresh K

    2014-01-01

    Right iliac fossa (RIF) pain is one of the most common presenting complaints faced by general surgeons in the emergency department. Correct diagnosis and appropriate surgical intervention can often pose a challenge. A 12-year-old girl presented to the emergency department with a four day history of initially central acute abdominal pain, now localised in the RIF. During laparoscopy, the following findings were made: macroscopically dilated appendix, right and left gonads at the internal opening of the inguinal canal, empty pelvis with a rudimentary uterus on the right side. No evidence of fallopian tubes or connection of uterus to the vagina and broad based, non-inflamed Meckel's diverticulum. An incidental diagnosis of complete androgen insensitivity syndrome was made. Androgen insensitivity syndrome (AIS) is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and testes producing age-appropriate normal concentrations of androgens. This case report highlights the advantage of laparoscopy as a diagnostic and treatment tool in a twelve year old girl with multiple intra-abdominal findings. While the ultimate diagnosis responsible for her symptom of RIF pain was acute appendicitis, the additional diagnosis of CAIS and incidental Meckel's would have otherwise likely gone undetected. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  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. Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Kuiper, G. G.; Faber, P. W.; Schweikert, H. U.; van Rooij, H. C.; Zegers, N. D.; Hodgins, M. B.; Degenhart, H. J.; Trapman, J.; Brinkmann, A. O.

    1990-01-01

    Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G----T mutation in the splice donor site of

  13. Functional analysis of a novel androgen receptor mutation, Q902K, in an individual with partial androgen insensitivity.

    NARCIS (Netherlands)

    A. Umar (Arzu); C.A. Berrevoets (Cor); N.M. Van (Mai); M. van Leeuwen (Marije); M.M.P.J. Verbiest (Michael); W.J. Kleijer (Wim); D. Dooijes (Dennis); J.A. Grootegoed (Anton); S.L.S. Drop (Stenvert); A.O. Brinkmann (Albert)

    2005-01-01

    textabstractAndrogen insensitivity syndrome (AIS) is caused by defects in the androgen receptor (AR) that render the AR partially or completely inactive. As a result, embryonic sex differentiation is impaired. Here, we describe a novel mutation in the AR found in a patient with

  14. 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

  15. Mental Health and Disorders of Sex Development/Intersex Conditions in Iranian Culture: Congenital Adrenal Hyperplasia, 5-α Reductase Deficiency-Type 2, and Complete Androgen Insensitivity Syndrome.

    Science.gov (United States)

    Khorashad, Behzad S; Aghili, Zahra; Kreukels, Baudewijntje P C; Reid, Alistair G; Roshan, Ghasem M; Hiradfar, Mehran; Talaei, Ali; Cohen Kettenis, Peggy T

    2018-05-01

    Sixty-one patients (22 patients with congenital adrenal hyperplasia [CAH] with a mean age of 14.86 years [range, 5-23], 20 patients with 5-α reductase deficiency type 2 [5α-RD-2] with a mean age of 19.5 years [range, 5-29], and 19 patients with complete androgen insensitivity syndrome [CAIS] with a mean age of 18.26 years [range, 5-28]) were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia, the Structured Clinical Interview for DSM-IV Axis I, Axis II, and the Global Assessment Functioning Scale. All participants were female-assigned at birth. Ten patients (16.4%) transitioned to the male gender. Overall, 68% of patients had one or more lifetime Axis I disorders, including 63.6% of the CAH participants, 90% of 5α-RD-2 participants, and 52.6% of the CAIS participants. The most commonly observed were affective disorders (27.9%), gender identity disorder (27.9%), and anxiety (16.4%). Our study demonstrates that mental health of Iranian patients with DSD is at risk. This might be due to the fact that patients with DSD conditions are mostly treated medically and their mental health is often superficially addressed in developing countries such as Iran, at least in the past. We argue that it is important to pay attention to the mental health issues of patients with DSD and focus on specific issues, which may vary cross-culturally.

  16. 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.

  17. Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer.

    Science.gov (United States)

    Disciglio, Vittoria; Devecchi, Andrea; Palumbo, Orazio; Carella, Massimo; Penso, Donata; Milione, Massimo; Valle, Giorgio; Pierotti, Marco Alessandro; Vitellaro, Marco; Bertario, Lucio; Canevari, Silvana; Signoroni, Stefano; De Cecco, Loris

    2016-06-07

    Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described. Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers. By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

  18. 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.

  19. Metabolic syndrome in androgenic alopecia.

    Science.gov (United States)

    Gopinath, Hima; Upadya, Gatha M

    2016-01-01

    Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. To study the association between metabolic syndrome and early-onset androgenic alopecia. A hospital-based analytical cross-sectional study was done on men in the age group of 18-55 years. Eighty five clinically diagnosed cases with early-onset (alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t-test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS) version 17.00. Metabolic syndrome was seen in 19 (22.4%) patients with androgenic alopecia and 8 (9.4%) controls (P = 0.021). Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia.

  20. Three siblings with complete androgen insensitivity syndrome

    African Journals Online (AJOL)

    2013-01-13

    Jan 13, 2013 ... Male: 1.2-8.6 IU/l. Testosterone. 22.9. Female: 0.34-2.6 nmol/l. Male: 6.07-27.1 nmol/l. Sex hormone-binding globulin. 158.1. Female: 18.2-135.7 nmol/l. Male: 13.2-89.5 nmol/l ... The serum testosterone values were in the adult male range, with an .... The majority present later during puberty with primary.

  1. 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

  2. Complete direct sequencing of the entire AR gene in 45 unrelated patients with androgen insensitivity syndrome: Mutations identified in 32 patients (18 novel mutations), no mutation detected in 13 other patients (29%)

    Energy Technology Data Exchange (ETDEWEB)

    Mebarki, F.; Forest, M.G.; Josso, N. [Hospital Debrousse, Lyon (France)] [and others

    1994-09-01

    The androgen insensivity syndrome (AIS) is a recessive X-linked disorder resulting from a deficient function of the androgen receptor (AR). The human AR gene has 3 functional domains: N-terminal encoded by exon 1, DNA-binding domain encoded by exons 2 and 3, and androgen-binding domain encoded by exons 4 to 8. In order to characterize the molecular defects of the AR gene in AIS, the entire coding regions and the intronic bording sequences of the AR gene were amplified by PCR before automatic direct sequencing in 45 patients. Twenty seven different point mutations were found in 32 unrelated AIS patients: 18 with a complete form (CAIS), 14 with a partial form (PAIS); 18 of these mutations are novel mutations, not published to date. Only 3 mutations were repeatedly found: R804H in 3 families; M780I in 3 families and R774C in 2 families. For 26 patients out of the 32 found to have a mutation, maternal DNA was collected and sequenced: 6 de novo mutations were detected (i.e. 23% of the cases). Finally, no mutation was detected in 13 patients (29%): 7 with CAIS and 6 familial severe PAIS. The latter all presented with perineal hypospadias, micropenis, 4 out of 6 being raised as girl. Diagnosis of AIS in these 13 families in whom no mutation was detected is supported by the following criteria: clinical data, familial history (2 or 3 index cases in the same family), familial segregation of the polymorphic CAG repeat of the AR gene. Mutations in intronic regions or the promoter of the AR gene could not explain all cases of AIS without mutations in the AR coding regions, because AR binding (performed in 9 out of 13) was normal in 6, suggesting the synthesis of an AR protein. This situation led us to speculate that another X-linked factor associated with the AR could be implicated in some cases of AIS.

  3. Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines.

    Science.gov (United States)

    Wilson, Stephen; Qi, Jianfei; Filipp, Fabian V

    2016-09-14

    Sequence motifs are short, recurring patterns in DNA that can mediate sequence-specific binding for proteins such as transcription factors or DNA modifying enzymes. The androgen response element (ARE) is a palindromic, dihexameric motif present in promoters or enhancers of genes targeted by the androgen receptor (AR). Using chromatin immunoprecipitation sequencing (ChIP-Seq) we refined AR-binding and AREs at a genome-scale in androgen-insensitive and androgen-responsive prostate cancer cell lines. Model-based searches identified more than 120,000 ChIP-Seq motifs allowing for expansion and refinement of the ARE. We classified AREs according to their degeneracy and their transcriptional involvement. Additionally, we quantified ARE utilization in response to somatic copy number amplifications, AR splice-variants, and steroid treatment. Although imperfect AREs make up 99.9% of the motifs, the degree of degeneracy correlates negatively with validated transcriptional outcome. Weaker AREs, particularly ARE half sites, benefit from neighboring motifs or cooperating transcription factors in regulating gene expression. Taken together, ARE full sites generate a reliable transcriptional outcome in AR positive cells, despite their low genome-wide abundance. In contrast, the transcriptional influence of ARE half sites can be modulated by cooperating factors.

  4. 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.

  5. Metabolic Syndrome, Androgens, and Hypertension

    OpenAIRE

    Moulana, Mohadetheh; Lima, Roberta; Reckelhoff, Jane F.

    2011-01-01

    Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and met...

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

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 4. Three novel and two known androgen receptor gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. BALACHANDRAN SARANYA GUNASEKARAN BHAVANI BRINDHA ARUMUGAM MEENA JAYASHANKAR ...

  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. 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.

  11. MicroRNAs related to androgen metabolism and polycystic ovary syndrome

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  12. 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)

  13. Inhibition of Androgen Receptor Expression with Small Interfering RNA Enhances Cancer Cell Apoptosis by Suppressing Survival Factors in Androgen Insensitive, Late Stage LNCaP Cells

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    2013-01-01

    Full Text Available Introduction.The aim was to evaluate the changes of androgen receptor (AR expression quantitatively and to identify influence of AR on cancer related survival markers in LNCap cell line. Materials and Methods. We compared expressions of AR, heat shock protein 27 (HSP27, clusterin (CLU, glucose-related protein 78 (GRP78, and cellular FLICE-like inhibitory protein (c-FLIP and their genes between es-LNCaP (less than 33 times subcultured, L-33, ls-LNCaP (over 81 times subcultured, H-81, and si-LNCaP (AR siRNA transfected ls-LNCaP by Western blotting and RT-PCR. Results. The expressions of AR, HSP27, CLU, GRP78, and c-FLIP were increased in ls-LNCaP compared with es-LNCaP (AR, 157%; HSP27, 132%; CLU, 146%; GRP78, 138%; c-FLIP, 152%. However, in si-LNCaP cell line, protein expressions were reversed to the level of es-LNCaP cell lines (25, 102, 109, 98, and 101%, and gene expressions on real-time PCR were also reversed to the expression level of es-LNCaP (ls-LNCaP: 179, 156, 133, 123, and 167%; si-LNCaP: 22, 93, 103, 112, and 107%. Conclusions. This finding suggests that androgen receptor can be related to the increased expression of cancer related survival markers such as HSP27, GRP78, CLU, and c-FLIP in late stage prostate cancer, and also inhibition of AR gene can be a therapeutic target in this stage of cancer.

  14. 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

  15. Caution for anabolic androgenic steroid use: a case report of multiple organ dysfunction syndrome.

    Science.gov (United States)

    Unai, Shinya; Miessau, Joseph; Karbowski, Pawel; Baram, Michael; Cavarocchi, Nicholas C; Hirose, Hitoshi

    2013-12-01

    We report a 42-year-old male amateur body builder and user of anabolic androgenic steroids, who developed ARDS, acute kidney injury, and refractory supraventricular tachycardia. He required extracorporeal membrane oxygenation, continuous veno-venous hemodialysis, and catheter ablation. We believe that long-term anabolic androgenic steroid abuse predisposed the patient to multiple organ dysfunction syndrome, from its immunomodulatory effects in an otherwise healthy patient. Anabolic androgenic steroid use should be part of the history taking process, since it may complicate diagnosis, disease progression, and prognosis.

  16. 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...

  17. Role of androgen ratios in the prediction of the metabolic phenotype in polycystic ovary syndrome.

    Science.gov (United States)

    Minooee, Sonia; Ramezani Tehrani, Fahimeh; Tohidi, Maryam; Azizi, Fereidoun

    2017-05-01

    To identify the androgen ratio that best predicts insulin resistance and metabolic syndrome among women with polycystic ovary syndrome (PCOS). Data for 180 women with PCOS and 180 healthy controls were extracted from two previous studies in Iran (conducted during 2008-2010 and 2011-2013). The diagnosis of PCOS was based on the Rotterdam criteria. The serum concentration of different androgens was measured. Receiver operating characteristic curve analysis was used to assess the ability of various androgen ratios to predict insulin resistance and metabolic syndrome. Among women with PCOS, the testosterone-to-androstenedione ratio was the best predictor of insulin resistance (sensitivity 0.83, specificity 0.42) and metabolic syndrome (sensitivity 0.85, specificity 0.70). Among healthy controls, the ratio of free androgen index to testosterone was the best predictor of insulin resistance (sensitivity 0.84, specificity 0.33) and metabolic syndrome (sensitivity 0.91, specificity 0.17). The prediction of insulin resistance and metabolic syndrome among women with PCOS was best accomplished with the testosterone-to-androstenedione ratio. © 2017 International Federation of Gynecology and Obstetrics.

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

    DEFF Research Database (Denmark)

    Bojesen, A; Hertz, Jens Michael; Gravholt, Claus Højbjerg

    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...

  19. 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.

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

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    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.

  1. 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.

  2. 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.

  3. 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.

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

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    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.

  5. Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer

    Science.gov (United States)

    2005-04-01

    07$15.00/0 Printed m U 8 .A. Molecular Endocrino logy 21 (12):2864- 2876 Copyright C’l 2007 by The Endocrine Society d ol: 10.121G/ me.2007-0094...mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART -27 coacti- vator function. Mol Endocrino l 19

  6. 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

  7. 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

    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 (PCOS)-population.

  8. Aspects of androgen replacement therapy for the treatment of hypogonadism in men with diabetes and metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Роман Викторович Роживанов

    2015-04-01

    Full Text Available The article presents the results of studies of efficacy and safety of androgen therapy for hypogonadism, metabolic syndrome and type 2diabetes mellitus in men. In the study was used testosterone undecanoate therapy which causes reduction of obesity, a decrease in theseverity of the other components of the metabolic syndrome, improving glycemic profile without significant side effects. Nevertheless,this therapy requires monitoring and management for risk factors.

  9. 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

  10. 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

  11. 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

  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......Context: Androgen signaling via the androgen receptor (AR) is essential for normal testis development and male reproductive functions. We describe a rare family with 3 males affected by a mild disorder of sex determination compatible with testicular dysgenesis syndrome (TDS), including subfertility.......Participants: The proband, his first cousin, and a nephew underwent a detailed clinical investigation including genetic tests, whereas four female members of the family were tested for the specific AR mutation.Results: A novel AR mutation, c.2214T>G;p.Ile738Met, was identified in the affected family members. Functional...

  13. 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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Manea Mirela

    2015-10-01

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

  16. 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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Stanisław Fracki

    2005-02-01

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

  19. The association of serum androgens and insulin resistance with fat distribution in polycystic ovary syndrome.

    Science.gov (United States)

    Yucel, Aykan; Noyan, Volkan; Sagsoz, Nevin

    2006-05-01

    The aim of the study was to compare the body fat distribution of women with polycystic ovary syndrome (PCOS) with age and body mass index matched healthy controls and to investigate if androgens and insulin resistance associated with fat distribution. Thirty-three PCOS and 21 age and body mass index (BMI) matched healthy control women were evaluated in terms of body fat distribution with dual X-ray absorpsiometry (DEXA). Blood samples were obtained for follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, thyroid stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), free testosterone, sex hormone binding globulin (SHBG), insulin and glucose levels. A 75 g 2 h glucose tolerance test was performed for each woman. Insulin resistance was estimated by fasting insulin level, fasting glucose/insulin ratio and 75 g 2 h glucose tolerance test. The Student's t-test and Mann-Whitney U-test were used to compare the groups. Pearson and Spearman rank correlation coefficients were calculated for normally and nonnormally distributed variables, respectively. Partial correlation coefficients were calculated using age and BMI as covariates. Fat mass in trunk and arms were significantly higher in patients with PCOS (p fat mass in trunk to fat mass in legs were significantly higher in patients with PCOS (p testosterone was found to be positively correlated with fat mass in arms (r = 0.401, p testosterone and fat mass in arms (r = 0.5964, p testosterone level is positively correlated with the fat mass in arms in women with PCOS.

  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. 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.

  3. [Evaluation of relationships between plasma androgens level and clinical signs of hipoandrogenism according to age and comorbidity of metabolic syndrome in men].

    Science.gov (United States)

    Herman, Waldemar Adam; Krzoska, Anna; Pawliczak, Elzbieta; Roszak, Magdalena; Łacka, Katarzyna

    2014-01-01

    The prevalence of late-onset hipogonadism (LOH) in men is not accurately determined and may be overestimated. Androgen deficiency is causally linked to insulin resistance, regardless of age. Clinical signs of androgen deficiency are not uniquely specific for LOH. The aim of this study was to assess the correlations between androgen serum levels and clinical symptoms of andropenia depending on the age. We evaluated the relationships between the frequency of LOH and metabolic syndrome (MS) and compared different methods of androgen assessment in the context of their clinical relevance. In 153 randomly selected men aged 40 to 70 years adrenal (DHEA and DHEAS) and gonadal (total-TT and free testosterone-FT) androgens were evaluated and compared with free (c-FT) and bioavailable testosterone (c-BAT) calculated with a mathematical algorithm. European Male Aging Study criteria for the diagnosis of LOH were used. TT concentration (r = -0.074, p = 0.363) and FT (r = -0.054, p = 0.505) did not correlate with age, in contrast to the c-FT (r = -0.280, p = 0.0005 ), c-BAT (r = -0.297, p = 0.0002) and both adrenal androgens: DHEA (r = -0.318, p = 0.00001) and DHEAS (r = -0.506, p < 0.00001). The clinical signs suggesting andropenia were found in 31.4% of participants and androgen deficiency in 28.8% of men. The incidence of these signs increased significantly with the age of respondents. In contrast, the criteria of LOH in the entire group were fulfilled by only 6.5% of men. Men diagnosed with MS showed significantly lower TT plasma levels: 5.05 (3.70-6.45) vs. 6.30 (5.40-8.30), p < 0.0001--contrary to the FT, c-FT, c-BAT as well as DHEA/DHEAS serum levels, regardless of age. Men meeting the full criteria for LOH (clinical symptoms and laboratory-confirmed hipoandrogenemia) revealed more than a five-fold higher risk of metabolic syndrome in relation to others (OR = 5.533, 95% CI: 1.134-27.+ 01). Total, free, calculated-free and calculated-bioavailable testosterone serum

  4. 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.

  5. 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)

  6. Polycystic ovary syndrome (PCOS) : role of androgens and obesity on placental function and fetal development

    OpenAIRE

    Fornes, Romina

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting women in childbearing age with a prevalence of up to 17.8%. The syndrome is characterized by hyperandrogenism, irregular cycles and polycystic ovaries. The etiology of PCOS is unclear, but it is thought to be multifactorial. There is a strong association between hyperinsulinemia and hyperandrogenism in PCOS, but the mechanisms behind their relationship with PCOS are not fully understood. Obe...

  7. 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.

  8. 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....

  9. Estradiol negative and positive feedback in a prenatal androgen-induced mouse model of polycystic ovarian syndrome.

    Science.gov (United States)

    Moore, Aleisha M; Prescott, Melanie; Campbell, Rebecca E

    2013-02-01

    Gonadal steroid hormone feedback is impaired in polycystic ovarian syndrome (PCOS), a common endocrine disorder characterized by hyperandrogenism and an associated increase in LH pulse frequency. Using a prenatal androgen (PNA)-treated mouse model of PCOS, we aimed to investigate negative and positive feedback effects of estrogens on the hypothalamic-pituitary axis regulation of LH. PNA-treated mice exhibited severely disrupted estrous cycles, hyperandrogenism, significantly reduced fertility, and altered ovarian morphology. To assess the negative feedback effects of estrogens, LH was measured before and after ovariectomy and after estradiol (E2) administration. Compared with controls, PNA-treated mice exhibited a blunted postcastration rise in LH (P positive feedback, control and PNA-treated GnRH-green fluorescent protein transgenic mice were subjected to a standard ovariectomy with E2-replacement regimen, and both plasma and perfusion-fixed brains were collected at the time of the expected GnRH/LH surge. Immunocytochemistry and confocal imaging of cFos and green fluorescent protein were used to assess GnRH neuron activation and spine density. In the surged group, both control and PNA-treated mice had significantly increased LH and cFos activation in GnRH neurons (P positive and -negative GnRH neurons to examine whether there was an increase in spine density in cFos-expressing GnRH neurons of surged mice as expected. A significant increase in spine density in cFos-expressing GnRH neurons was evident in control animals; however, no significant increase was observed in the PNA-treated mice because spine density was elevated across all GnRH neurons. These data support that PNA treatment results in a PCOS-like phenotype that includes impaired E2-negative feedback. Additionally, although E2-positive feedback capability is retained in PNA mice, elevated GnRH neuron spine density may reflect altered synaptic regulation.

  10. 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...

  11. 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.

  12. 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

  13. 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

  14. 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 <10 mm in diameter, or visualized all follicles, were included. RESULTS Studies addressing women recruited from the general population and studies comparing control and PCOS populations with appropriate statistics were convergent towards setting the threshold for increased FNPO at ≥25 follicles, in women aged 18-35 years. These studies suggested maintaining the threshold for increased OV at ≥10 ml. Critical analysis of the literature showed that OV had less diagnostic potential for PCOM compared with FNPO. The review did not identify any additional diagnostic advantage for other ultrasound metrics such as specific measurements of ovarian stroma or blood flow. Even though serum concentrations of anti-Müllerian hormone (AMH) showed a diagnostic performance for PCOM that was equal to or better than that of FNPO in some series, the accuracy and reproducibility issues of currently available AMH assays preclude the establishment of a threshold value for its use as a surrogate marker of

  15. 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.

  16. 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.

  17. 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.

  18. 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) ...

  19. 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...

  20. 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.

  1. Androgen receptor expression as a prognostic and predictive ...

    African Journals Online (AJOL)

    Purpose: It is clear that triple-negative breast cancer (TNBC) tumors are heterogeneous group, but clinically important sub-sets have begun to emerge. We investigate the immunohistochemical expression of androgen receptor (AR) among those hormonal insensitive groups which have only the option of chemotherapy.

  2. 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

  3. Obesity and androgens: facts and perspectives.

    Science.gov (United States)

    Pasquali, Renato

    2006-05-01

    This review discusses androgen status in male and female obesity, according to their specific phenotype, and the main mechanisms responsible. Published data in the literature of the last 20 years represented the basis of most of the data and concepts incorporated in the review. Obesity is associated with profound alterations in androgen secretion, transport, metabolism, and action, according to a dichotomous behavior depending on sex. Obese men are characterized by a progressive decrease of testosterone levels with increasing body weight, whereas obese women, particularly those with the abdominal phenotype, tend to develop a condition of functional hyperandrogenism. Reduced sex hormone-binding globulin synthesis and circulating blood levels represent the sole common mechanism which is responsible in both sexes. Among other still partially undefined factors, mechanisms potentially responsible for the sex dichotomy in androgen levels involve specific alterations of gonadotropin secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen receptors, specific steroidogenic enzymes in the peripheral tissues, and, possibly, ghrelin. In both sexes, androgens play an important role in determining the sex-dependent pattern of body fat distribution. Moreover there are theoretical possibilities that low testosterone in men and high free testosterone fraction in women may play a role in the development of the metabolic syndrome. This is exemplified by the well defined association between obesity and other features of the metabolic syndrome in women with polycystic ovary syndrome and in hypogonadal men. The effects of androgen and antiandrogens in obese men and women also represent arguments in favor of this association. Given the fundamental role of sex hormones in the regulation of body composition, fuel homeostasis, and reproduction in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different

  4. Comparison of the metabolic parameters and androgen level of umbilical cord blood in newborns of mothers with polycystic ovary syndrome and controls

    Directory of Open Access Journals (Sweden)

    Ferdous Mehrabian

    2012-01-01

    Full Text Available Background: This study aimed to assess the metabolic parameters and androgen concentration in the cord blood of newborns of mothers with polycystic ovary syndrome (PCOS in comparison with controls. Materials and Methods: This cross-sectional study was conducted in 2010-2011 in Isfahan, Iran. Biochemical tests were conducted on 40 infants, born from singleton pregnancies in women with PCOS and an equal number of controls. Results: The mean weight gain during pregnancy was higher in women with PCOS than in controls (16.02 ± 4.39 vs. 9.10 ± 2.20 kg, respectively, P < 0.0001. The mean birth weight was lower in newborns of mothers with PCOS than in controls (2905.25 ± 415.59 vs. 3223.25 ± 425.02 vs. grams, respectively, P = 0.001. The mean testosterone was higher in cord blood of newborns of PCOS women than in controls (5.58 ± 3.20 vs. 2.28 ± 0.62 pg/ml, P < 0.0001. Triglycerides and LDL-C were lower in cord blood of newborns, born from PCOS women than in controls (P = 0.001. The birth weight of the newborns of PCOS mothers was negatively correlated to free testosterone of cord blood (R = -0. 26, P = 0.04. Conclusion: The metabolic aberration in PCOS might influence fetal birth weight and cord blood lipid profile. These disorders may be caused by an exposure to elevated testosterone level during fetal life. The offspring of PCOS women may be at higher risk for chronic diseases in later life. The clinical impact of our findings should be confirmed in future longitudinal studies.

  5. Tissue selectivity and potential clinical applications of trenbolone (17beta-hydroxyestra-4,9,11-trien-3-one): A potent anabolic steroid with reduced androgenic and estrogenic activity.

    Science.gov (United States)

    Yarrow, Joshua F; McCoy, Sean C; Borst, Stephen E

    2010-06-01

    Recently, the development of selective androgen receptor modulators (SARMs) has been suggested as a means of combating the deleterious catabolic effects of hypogonadism, especially in skeletal muscle and bone, without inducing the undesirable androgenic effects (e.g., prostate enlargement and polycythemia) associated with testosterone administration. 17beta-Hydroxyestra-4,9,11-trien-3-one (trenbolone; 17beta-TBOH), a synthetic analog of testosterone, may be capable of inducing SARM-like effects as it binds to androgen receptors (ARs) with approximately three times the affinity of testosterone and has been shown to augment skeletal muscle mass and bone growth and reduce adiposity in a variety of mammalian species. In addition to its direct actions through ARs, 17beta-TBOH may also exert anabolic effects by altering the action of endogenous growth factors or inhibiting the action of glucocorticoids. Compared to testosterone, 17beta-TBOH appears to induce less growth in androgen-sensitive organs which highly express the 5alpha reductase enzyme (e.g., prostate tissue and accessory sex organs). The reduced androgenic effects result from the fact that 17beta-TBOH is metabolized to less potent androgens in vivo; while testosterone undergoes tissue-specific biotransformation to more potent steroids, dihydrotestosterone and 17beta-estradiol, via the 5alpha-reductase and aromatase enzymes, respectively. Thus the metabolism of 17beta-TBOH provides a basis for future research evaluating its safety and efficacy as a means of combating muscle and bone wasting conditions, obesity, and/or androgen insensitivity syndromes in humans, similar to that of other SARMs which are currently in development. Published by Elsevier Inc.

  6. 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 ...

  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 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. 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.

  11. 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

  12. 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

  13. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of

  14. Androgen receptor abnormalities

    NARCIS (Netherlands)

    Brinkmann, A. O.; Kuiper, G. G.; Ris-Stalpers, C.; van Rooij, H. C.; Romalo, G.; Trifiro, M.; Mulder, E.; Pinsky, L.; Schweikert, H. U.; Trapman, J.

    1991-01-01

    The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the

  15. Androgen receptor phosphorylation

    NARCIS (Netherlands)

    G.G.J.M. Kuiper (George)

    1995-01-01

    textabstractMany physiological processes in organisms are regulated by a relatively small number of steroid honnones. Androgens are the so-called male sex steroid hormones which control growth, differentiation and functions of male reproductive and accessory sex tissues. Androgens are mainly

  16. 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

    2017-11-06

    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 PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved. IRCT2016062710826N19.

  17. 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.

  18. Ovarian overproduction of androgens

    Science.gov (United States)

    ... an ovarian or adrenal tumor. Outlook (Prognosis) Treatment success depends on the cause of excess androgen production. ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  19. Androgens and menopause.

    Science.gov (United States)

    Shulman, L P

    2009-12-01

    The cessation of ovarian sex steroidigenesis, either as result as surgical extirpation, certain medical therapies or the gradual cessation of ovarian function, leads to menopause with all its associated physiological, physical and lifestyle changes. The changing hormonal milieu of menopause is most commonly associated with declining levels of estrogens. However, ovarian senescence also results in declining levels of androgens. Indeed, it is the loss of physiological levels of estrogens and androgens that result in the varied signs and symptoms of menopause including vasomotor symptoms, bone mineral density loss, reduced interest in sex, alterations in mood and energy and hair loss, among others. This paper will provide a review of the role of androgens in the menopause and assess the potential of androgen therapies in the management of the menopause.

  20. Therapeutic androgen receptor ligands

    Science.gov (United States)

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs). PMID:16604181

  1. Benchtop Insensitivity: First Steps with Shocked PETN

    National Research Council Canada - National Science Library

    Lewis, William K; Fajardo, Mario E

    2008-01-01

    "Insensitive Munitions (IM) are conventional weapons and ordnance that fulfill their performance objectives while minimizing collateral damage if exposed to stimuli including fires, impact and shock threats...

  2. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shtutman Michael

    2010-04-01

    Full Text Available Abstract Background Castration resistant prostate cancer (CRPC develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881 restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to

  3. 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

  4. 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.

  5. Androgen secreting adrenocortical tumours.

    Science.gov (United States)

    Wolthers, O D; Cameron, F J; Scheimberg, I; Honour, J W; Hindmarsh, P C; Savage, M O; Stanhope, R G; Brook, C G

    1999-01-01

    Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. To assess the presentation, histology, and clinical behaviour of these tumours. Two tertiary referral centres. Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. Twenty three girls and seven boys aged 0-14 years. Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.

  6. Insensitivity to Scope in Contingent Valuation Studies

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Lindholt, Jes Sanddal; Gyrd-Hansen, Dorte

    2012-01-01

    and mental budgeting explain scope insensitivity there are grounds for rejecting valuations, whereas other factors such as the alternative theoretical framework of regret theory may render insensitivity to scope a result of rational thinking. It is concluded that future contingent valuation studies should......Background: The credibility of contingent valuation studies has been questioned because of the potential occurrence of scope insensitivity, i.e. that respondents do not react to higher quantities or qualities of a good. Objective: The aim of this study was to examine the extent of scope...... insensitivity and to assess the relevance of potential explanations that may help to shed light on how to appropriately handle this problem in contingent valuation studies. Methods: We surveyed a sample of 2004 men invited for cardiovascular disease screening. Each respondent had three contingent valuation...

  7. Synthetic inhibitors of CDKs induce different responses in androgen sensitive and androgen insensitive prostatic cancer cell lines

    Czech Academy of Sciences Publication Activity Database

    Maďarová, J.; Lukešová, M.; Hlobilková, A.; Strnad, Miroslav; Vojtěšek, B.; Lenobel, R.; Hajdúch, M.; Murray, P. G.; Perera, S.; Kolář, Z.

    2002-01-01

    Roč. 55, č. 4 (2002), s. 227-234 ISSN 1366-8714 R&D Projects: GA ČR GA301/02/0475 Institutional research plan: CEZ:AV0Z5038910 Keywords : synthetic CDK inhibitors * cell cycle * apoptosis Subject RIV: EB - Genetics ; Molecular Biology

  8. Comparative safety evaluation of selective androgen receptor modulators and anabolic androgenic steroids.

    Science.gov (United States)

    Choi, Seul Min; Lee, Byung-Mu

    2015-01-01

    Anabolic androgenic steroids (AASs) have been in use for decades for the treatment of short stature, severe burns, HIV wasting syndrome, osteoporosis, and anemia. However, their lack of selective effects on certain symptoms and unfavorable pharmacokinetic properties has limited their long-term usage in clinics. Selective androgen receptor modulators (SARMs) have some advantages over AASs; they are highly specific for androgen receptors, are orally available, and, most importantly, act as strong receptor agonists in skeletal muscle and bone, and as weak agonists or antagonists in androgen-responsive tissues such as the prostate and sebaceous glands. The exact molecular mechanism, however, has not been fully elucidated. This article includes a toxicological review of major AASs, and a comparative safety analysis of major AASs and SARMs in clinical trials to evaluate the therapeutic potential of SARMs. Based on the robust tissue selectivity of SARMs over AASs, they are worth considering as a promising therapeutic option for the treatment of various muscle-wasting diseases.

  9. 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

  10. 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.

  11. 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

  12. Androgens and androgen receptor action in skin and hair follicles.

    Science.gov (United States)

    Ceruti, Julieta María; Leirós, Gustavo José; Balañá, María Eugenia

    2018-04-15

    Beyond sexual functions, androgens exert their action in skin physiology and pathophysiology. Skin cells are able to synthesize most active androgens from gonadal or adrenal precursors and the enzymes involved in skin steroidogenesis are implicated both in normal or pathological processes. Even when the role of androgens and androgen receptor (AR) in skin pathologies has been studied for decades, their molecular mechanisms in skin disorders remain largely unknown. Here, we analyze recent studies of androgens and AR roles in several skin-related disorders, focusing in the current understanding of their molecular mechanisms in androgenetic alopecia (AGA). We review the molecular pathophysiology of type 2 5α-reductase, AR coactivators, the paracrine factors deregulated in dermal papillae (such as TGF-β, IGF 1, WNTs and DKK-1) and the crosstalk between AR and Wnt signaling in order to shed some light on new promising treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity.

    Science.gov (United States)

    Adams, David R; Yuan, Hongjie; Holyoak, Todd; Arajs, Katrina H; Hakimi, Parvin; Markello, Thomas C; Wolfe, Lynne A; Vilboux, Thierry; Burton, Barbara K; Fajardo, Karin Fuentes; Grahame, George; Holloman, Conisha; Sincan, Murat; Smith, Ann C M; Wells, Gordon A; Huang, Yan; Vega, Hugo; Snyder, James P; Golas, Gretchen A; Tifft, Cynthia J; Boerkoel, Cornelius F; Hanson, Richard W; Traynelis, Stephen F; Kerr, Douglas S; Gahl, William A

    2014-11-01

    The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith-Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. 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.

  15. 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

    -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.......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...... chromosome abnormalities (46,XX males; 47,XYY)(n = 4) and normal karyotypes (46,XY) (n = 13). The reference range for the AR-copy number was established as 0.8-1.2 for one copy and 1.7-2.3 for two copies. The qPCR results were within the reference range in 17/18 samples (94%) or 30/31 (97%) samples with one...

  16. Androgen receptor functional analyses by high throughput imaging: determination of ligand, cell cycle, and mutation-specific effects.

    Directory of Open Access Journals (Sweden)

    Adam T Szafran

    Full Text Available Understanding how androgen receptor (AR function is modulated by exposure to steroids, growth factors or small molecules can have important mechanistic implications for AR-related disease therapies (e.g., prostate cancer, androgen insensitivity syndrome, AIS, and in the analysis of environmental endocrine disruptors.We report the development of a high throughput (HT image-based assay that quantifies AR subcellular and subnuclear distribution, and transcriptional reporter gene activity on a cell-by-cell basis. Furthermore, simultaneous analysis of DNA content allowed determination of cell cycle position and permitted the analysis of cell cycle dependent changes in AR function in unsynchronized cell populations. Assay quality for EC50 coefficients of variation were 5-24%, with Z' values reaching 0.91. This was achieved by the selective analysis of cells expressing physiological levels of AR, important because minor over-expression resulted in elevated nuclear speckling and decreased transcriptional reporter gene activity. A small screen of AR-binding ligands, including known agonists, antagonists, and endocrine disruptors, demonstrated that nuclear translocation and nuclear "speckling" were linked with transcriptional output, and specific ligands were noted to differentially affect measurements for wild type versus mutant AR, suggesting differing mechanisms of action. HT imaging of patient-derived AIS mutations demonstrated a proof-of-principle personalized medicine approach to rapidly identify ligands capable of restoring multiple AR functions.HT imaging-based multiplex screening will provide a rapid, systems-level analysis of compounds/RNAi that may differentially affect wild type AR or clinically relevant AR mutations.

  17. Clinical and genetic characterization of six cases with complete ...

    Indian Academy of Sciences (India)

    JING HE

    2017-08-31

    Aug 31, 2017 ... Keywords. androgen receptor; complete androgen insensitivity syndrome; mutation; karyotype analysis; DNA sequencing. Introduction. Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease, which is characterized by par- tial or complete cell resistance to androgens (Galani et al.

  18. ANDROGEN LEVELS IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    M. Valadan

    2006-08-01

    Full Text Available Preeclampsia is a major cause of morbidity and mortality during pregnancy. Several independent investigators have demonstrated the association of androgens with hypertension. The main purpose of this study was to determine whether maternal levels of sex hormones, especially testosterone, are higher in patients with preeclampsia than in matched normotensive control subjects. Serum levels of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S and estradiol were measured in 60 subjects in the 3rd trimester of pregnancy with documented preeclampsia (including 30 cases of mild and 30 cases of severe preeclampsia and 60 healthy normotensive women with similar maternal and gestational ages and body mass index (BMI and neonatal sex. All subjects were primigravid with singleton pregnancies. Cases of polycystic ovary (PCO, diabetes, chronic hypertension and chronic systemic diseases such as lupus and patients using steroid hormones and anti-hypertensive drugs were excluded. Levels of testosterone, DHEA-S and estradiol were not higher in primigravid women with preeclampsia than in normotensive women with similar gestational and maternal ages, BMI and neonatal sex. There were no significant differences in sex hormones measured between groups of mild and severe preeclampsia and normotensive women. There were also no significant differences in sex hormone levels according to neonatal sex. These findings are against the hypothesis of mediating or amplifying role of high androgen levels in pathophysiology of preeclampsia.

  19. 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

  20. 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…

  1. Photonic crystal based polarization insensitive flat lens

    Science.gov (United States)

    Turduev, M.; Bor, E.; Kurt, H.

    2017-07-01

    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 0.25λ) 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

  2. Insensitive TATP Training Aid by Microencapsulation

    Science.gov (United States)

    Oxley, J. C.; Smith, J. L.; Canino, J. N.

    2015-07-01

    There is a need in the explosives detection community for an insensitive, storage-stable source of triacetone triperoxide (TATP). To achieve this, the solvent evaporation microencapsulation technique was used to disperse TATP in a plastic matrix. This lowered the shock sensitivity greatly and prevented loss of TATP at room temperature, allowing for easy long-term storage. It was then demonstrated that pure TATP vapor was released on demand from the matrix by heating.

  3. 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.

  4. 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.

  5. 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?«

  6. Epsilon-insensitive fuzzy c-regression models: introduction to epsilon-insensitive fuzzy modeling.

    Science.gov (United States)

    Leski, Jacek M

    2004-02-01

    This paper introduces a new epsilon-insensitive fuzzy c-regression models (epsilonFCRM), that can be used in fuzzy modeling. To fit these regression models to real data, a weighted epsilon-insensitive loss function is used. The proposed method make it possible to exclude an intrinsic inconsistency of fuzzy modeling, where crisp loss function (usually quadratic) is used to match real data and the fuzzy model. The epsilon-insensitive fuzzy modeling is based on human thinking and learning. This method allows easy control of generalization ability and outliers robustness. This approach leads to c simultaneous quadratic programming problems with bound constraints and one linear equality constraint. To solve this problem, computationally efficient numerical method, called incremental learning, is proposed. Finally, examples are given to demonstrate the validity of introduced approach to fuzzy modeling.

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

    Directory of Open Access Journals (Sweden)

    Haendler Bernard

    2008-12-01

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

  8. Insensitive Munitions (Les Munitions a Risque Attenue)

    Science.gov (United States)

    1992-07-01

    par un apporte par le confinement. saul eclat de masse plus elevee (par example, sphere d acier de 250 g). - Ilechauffement lent. qui peut reprasentar...ontrent que ~--~a- czone 1r o’ ~- l’en .,loppe en acier ordinaire est p~nalisante par 2 2 rapport au bloc flu puisque le s;euil de d~tor~ation Qn...511 Insensitive Munitions ( Les Munitions ’a Risque Att~nu6) Papet r presented ait the Propulsion atud Energetics Panel 7&h A Sftecialisis’AMeeting

  9. Androgens and obesity.

    Science.gov (United States)

    Allan, Carolyn A; McLachlan, Robert I

    2010-06-01

    As testosterone levels are frequently reduced in obesity, an understanding of the relationship between serum testosterone and adiposity is necessary in the clinical evaluation of these men, in particular when considering testosterone therapy. Population and interventional data suggest a bi-directional relationship exists between testosterone and obesity in men, with lower total testosterone and sex hormone binding globulin (SHBG) (and to a lesser extent free testosterone) levels than their nonobese peers; obesity having an impact at least as important as ageing. Abnormalities in the hypothalamo-pituitary-testicular axis are seen with increasing obesity. Weight loss in massive obesity increases testosterone levels but its role in mild-moderate obesity is unclear. Testosterone supplementation reduces total body fat in hypogonadal and ageing men although the effects on regional fat distribution are less well described. Favourable changes in total body fat and regional fat distribution suggest a potential role for testosterone in obesity. However, lifestyle advice to achieve sustained weight loss should be the mainstay of management. Obese men with confirmed androgen deficiency can be offered treatment, whereas in those with low-normal testosterone levels more research is needed.

  10. 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.

  11. Delay-insensitive Multi-ring Structures

    DEFF Research Database (Denmark)

    Sparsø, Jens; Staunstrup, Jørgen

    1993-01-01

    algorithm. The vector multiplier has been laid out, submitted for fabrication, and successfully tested. This design is described in detail to illustrate the design and the performance analysis techniques. The design technique is based on a data flow approach using pipelines and rings that are composed......This paper describes a set of simple design and performance analysis techniques that have been successfully used to design a number of non-trivial delay-insensitive circuits. Examples are building blocks for digital filters and a vector multiplier using a serial-parallel multiply and accumulate......, and the main contribution of the paper is the comprehensive, integrated presentation of the material, including a thorough description of the vector multiplier design example....

  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...... 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...

  13. Androgen Receptor-Mediated Escape Mechanism from Androgen Ablation Therapy

    Science.gov (United States)

    2008-10-31

    except that no salmon sperm DNA was used as blocking reagent. The immunoprecipitated DNA and un- enriched input DNA were treated with RNase A and purified...A, Wang Y, Suzuki K, Mirosevich J, et al. (2005) Foxa1 and Foxa2 interact with the androgen receptor to regulate prostate and epididymal genes

  14. Androgenic function of the gonads in males with hyperthyroidism

    Directory of Open Access Journals (Sweden)

    S A Dogadin

    2013-06-01

    Full Text Available The aim of the study was to examine the levels of sex hormones in men with hyperthyroidism before and during treatment, and determining the feasibility of testosterone prescribing together with thyrostatic therapy, in men with androgen deficiency. The study involved 37 men with newly diagnosed diffuse toxic goiter and 16 healthy men, aged from 22 to 55 years. The testosterone (test. fractions (overall and free, SHBG, LH, FSH, estradiol and prolactin were determined. All hormones were measured before treatment and after 3, and then 6 months of thyrostatic ther apy. The overall test. level in men with hyperthyroidism was the same as in healthy subjects. Absolute and relative content of free test. fraction was significantly lower, but the SHBG level was higher than in healthy age relative men. The diagnostics of androgen deficiency syndrome was based on free test. determination. All patients with Diffuse toxic goiter the tiamazol (Merkazolil was appointed, while treatment with testosterone (Omnadren250 were offered to patients with low of free test. levels, but not all followed the recommendations. The groups were follow: patients without androgen deficiency ( n = 16, patients with androgen deficiency, taking only thyrostatic therapy ( n = 10, patients with androgen deficiency taken thyrostatic therapy simultaneously with testosterone therapy ( n = 11. The decreasing of free test. level was detected in 57% of examined men. In most cases (80% of that patients the 6 months thyrostatic therapy did not lead to free test. normalization. The free test. level concentration was nor mal only in 2 examined not receiving testosterone men (20% and in 9 (82%; χ 2 = 5.76; p = 0.017 among those who recieved both: thyrostatic and testosterone therapy. During treatment with Omnadren250 the relative content of free test. was significantly higher at 3 and 6 months of treatment. Using a questionnaire AMS confirmed the dynamics characteristics of androgen deficiency

  15. 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.

  16. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    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...

  17. Androgenic switch in barley microspores

    NARCIS (Netherlands)

    de Faria Maraschin, Simone

    2005-01-01

    Barley androgenesis represents an attractive system to study stress-induced cell differentiation and is a valuable tool for efficient plant breeding. The switch from the pollen developmental pathway towards an androgenic route involves several well-described morphological changes. However, little is

  18. 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

  19. Numerical Model of Detonation for Insensitive HE

    Science.gov (United States)

    Klimenko, Vladimir

    2011-06-01

    Most of modern munitions are filled by insensitive HE. However, mechanism of initiation of these HE is still unknown. IHE have not any pores and, therefore, hot spot mechanism does not work here. What is a mechanism working in this case? We have used 3D hydrocode to study process of shock wave loading of mixture of HMX grains with different binders (HMX/binder=88/12) and have determined formation of surface layers with increased plastic deformation. According to the dislocation mechanism of detonation (V. Klimenko, I. Kozyreva, J. Energetic Materials, 2010, v. 28, pp. 249-262) plastic deformation generates definite concentration of radicals. Surface layers have also increased temperature due to viscous work. So, these activated layers have increased temperature and number of radicals in comparison with values inside grains. Kinetic calculation has shown fast decomposition of these layers. As a result, the activated layer is ignited and this gives beginning of grain burning process. The developed two-stages mechanism has been incorporated into 2D hydrocode. The developed numerical model demonstrates high accuracy in simulation of detonation processes in IHE (in particular, PBXN-110 and B2241).

  20. 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.

  1. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)

    OpenAIRE

    Gao, Wenqing; Dalton, James T.

    2007-01-01

    Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contrib...

  2. Differential Mechanisms of Androgen Resistance

    Science.gov (United States)

    2007-12-01

    two infertile Finnish men. Fertility and Sterility , 79, Supple3, 2003. Miyake H, Hara I, Eto H.2005 Clinical outcome of maximum androgen blockade...identified in two infertile men (Lund et al 2003). It can be postulated that Q58L could change the conformation of the polyglutamide tract thereby...and PC3- LNCAP AR (C) tumour xenografts. 3 million cells in sterile PBS (1:1 ratio with Matrigel) were implanted s.c. into the flank of SCID mice

  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. 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.

  5. Major QTLs associated with green stem disorder insensitivity of soybean (Glycine max (L.) Merr.).

    Science.gov (United States)

    Yamada, Tetsuya; Shimada, Shinji; Hajika, Makita; Hirata, Kaori; Takahashi, Koji; Nagaya, Taiko; Hamaguchi, Hideo; Maekawa, Tomiya; Sayama, Takashi; Hayashi, Takeshi; Ishimoto, Masao; Tanaka, Junichi

    2014-12-01

    Green stem disorder (GSD) is one of the most serious syndromes affecting soybean (Glycine max) cultivation in Japan. In GSD, stems remain green even when pods mature. When soybean plants develop GSD, seed surfaces are soiled by tissue fluid and seed quality is deteriorated during machine harvesting. We performed quantitative trait locus (QTL) analyses for GSD insensitivity using recombinant inbred lines (RILs; n = 154) derived from a cross between an insensitive line ('Touhoku 129') and a sensitive leading cultivar ('Tachinagaha') during a 6-year evaluation. Three effective QTLs were detected. The influences of these QTLs were in the following order: qGSD1 (LG_H) > qGSD2 (LG_F) > qGSD3 (LG_L). At these three QTLs, 'Touhoku 129' genotypes exhibited more GSD insensitivity than 'Tachinagaha' genotypes. The lower incidence of GSD for 'Touhoku129' was attributable primarily to these three QTLs because RILs harboring a 'Touhoku 129' genotype at the three QTLs exhibited a GSD incidence similar to that of 'Touhoku 129.' Although a limitation of this study is that only one mapping population was evaluated, this QTL information and the flanking markers of these QTLs would be effective tools for resolving GSD in soybean breeding programs.

  6. 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.

  7. New insights into the androgen biotransformation in prostate cancer: A regulatory network among androgen, androgen receptors and UGTs.

    Science.gov (United States)

    Qin, Xuan; Liu, Mingyao; Wang, Xin

    2016-04-01

    Androgen, as one kind of steroid hormones, is pivotal in the hormone-sensitive cancer, such as prostate cancer (PCa). The synthesis, elimination, and bioavailability of androgen in prostate cells have been proved to be a main cause of the carcinogenesis, maintenance and deterioration of PCa. This review illustrates the outlines of androgen biotransformation, and further discusses the different enzymes, especially UDP-glucuronyltransferases (UGTs) embedded in both benign and malignant prostate cells, which catalyze the reactions. Although many inhibitors of the enzymes responsible for the synthesis of androgens have been developed into drugs to fight against PCa, the elimination procedures metabolized by the UGTs are less emphasized. Thus the regulatory network among androgen, androgen receptors (AR) and UGTs is carefully reviewed in this article, indicating the determinant effects of UGTs on prostatic androgens and the regulation of AR. Finally, the hypothesis is also put forward that the regulators of UGTs may be developed to accelerate the androgen elimination and benefit PCa therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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

  9. New Temperature-Insensitive Electronically-Tunable Grounded Capacitor Simulator

    OpenAIRE

    Muhammad Taher Abuelma'atti; Muhammad Haroon Khan

    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.

  10. 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.

  11. 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

  12. Androgens, body fat Distribution and Adipogenesis.

    Science.gov (United States)

    Zerradi, Mouna; Dereumetz, Julie; Boulet, Marie-Michèle; Tchernof, André

    2014-12-01

    Androgens are regulators of important adipocyte functions such as adipogenesis, lipid storage, and lipolysis. Through depot-specific impact on the cells of each fat compartment, androgens could modulate body fat distribution patterns in humans. Testosterone and dihydrotestosterone have been shown to inhibit the differentiation of preadipocytes to lipid-storing adipocytes in several models including primary cultures of human adipocytes from both men and women. Androgen effects have also been observed on some markers of lipid metabolism such as LPL activity, fatty acid uptake, and lipolysis. Possible depot-specific and sex-specific effects have been observed in some but not all models. Transformation of androgen precursors to active androgens or their inactivation by enzymes that are expressed and functional in adipose tissue may contribute to modulate the local availability of active hormones. These phenomena, along with putative depot-specific interactions with glucocorticoids may contribute to human body fat distribution patterns.

  13. Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen-sensitive prostate cancer cells.

    Science.gov (United States)

    Ghashghaei, Maryam; Paliouras, Miltiadis; Heravi, Mitra; Bekerat, Hamed; Trifiro, Mark; Niazi, Tamim M; Muanza, Thierry

    2018-01-01

    Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high-risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next-generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy. Using a number of androgen-dependent (LNCaP, PC3-T877A) and androgen-independent (C4-2, 22RV1, PC3, PC3-AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence. Our results indicated that either ENZA alone (in AR positive, androgen-dependent PCa cells) or in combination with ADT (in AR positive, hormone-insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4-2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule-dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT-induced phospho-γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT-induced apoptosis and senescence. Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes

  14. Aging male syndrome

    OpenAIRE

    Valer Donca; Antonia Macarie; Luminiţa Paşca; Elena Buzdugan; Constantin Bodolea; Dan Rădulescu; Sorin Crişan; Laurenţiu Stoicescu; Bogdan Neacşu; Steliana Donca

    2012-01-01

    Aging Male Syndrome is a medical condition through which men could pass between the ages of 35 and 65, when testosterone levelsin their body decline considerably. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout theworld. In contrast to female menopause, the process of aging in the male genital system is slow and highly variable between individuals. Thecharacteristic symptoms of Aging Male Syndrome include weakness, depression, fatigue and ...

  15. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 4. Three novel and two known androgen receptor gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. BALACHANDRAN SARANYA GUNASEKARAN BHAVANI BRINDHA ARUMUGAM MEENA JAYASHANKAR ...

  16. 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...

  17. 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

  18. Electroweak symmetry breaking via UV insensitive anomaly mediation

    International Nuclear Information System (INIS)

    Kitano, Ryuichiro; Kribs, Graham D.; Murayama, Hitoshi

    2004-01-01

    Anomaly mediation solves the supersymmetric flavor and CP problems. This is because the superconformal anomaly dictates that supersymmetry breaking is transmitted through nearly flavor-blind infrared physics that is highly predictive and UV insensitive. Slepton mass squareds, however, are predicted to be negative. This can be solved by adding D-terms for U(1) Y and U(1) B-L while retaining the UV insensitivity. In this paper we consider electroweak symmetry breaking via UV insensitive anomaly mediation in several models. For the minimal supersymmetric standard model we find a stable vacuum when tan β<1, but in this region the top Yukawa coupling blows up only slightly above the supersymmetry breaking scale. For the next-to-minimal supersymmetric standard model (NMSSM), we find a stable electroweak breaking vacuum but with a chargino that is too light. Replacing the cubic singlet term in the NMSSM superpotential with a term linear in the singlet we find a stable vacuum and viable spectrum. Most of the parameter region with correct vacua requires a large superpotential coupling, precisely what is expected in the 'Fat Higgs' model in which the superpotential is generated dynamically. We have therefore found the first viable UV complete, UV insensitive supersymmetry breaking model that solves the flavor and CP problems automatically: the Fat Higgs model with UV insensitive anomaly mediation. Moreover, the cosmological gravitino problem is naturally solved, opening up the possibility of realistic thermal leptogenesis

  19. 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.

  20. 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...

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

    National Research Council Canada - National Science Library

    Wang, Zhou

    2005-01-01

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

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

    National Research Council Canada - National Science Library

    Wang, Zhou

    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...

  3. 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...

  4. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline.

    Science.gov (United States)

    Wierman, Margaret E; Arlt, Wiebke; Basson, Rosemary; Davis, Susan R; Miller, Karen K; Murad, Mohammad H; Rosner, William; Santoro, Nanette

    2014-10-01

    To update practice guidelines for the therapeutic use of androgens in women. A Task Force appointed by the Endocrine Society, American Congress of Obestricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), European Society of Endocrinology (ESE), and International Menopause Society (IMS) consisting of six experts, a methodologist, and a medical writer. The Task Force commissioned two systematic reviews of published data and considered several other existing meta-analyses and trials. The GRADE methodology was used; the strength of a recommendation is indicated by a number "1" (strong recommendation, we recommend) or "2" (weak recommendation, we suggest). Multiple e-mail communications and conference calls determined consensus. Committees of the Endocrine Society, ASRM, ACOG, ESE, and IMS reviewed and commented on the drafts of the guidelines. We continue to recommend against making a diagnosis of androgen deficiency syndrome in healthy women because there is a lack of a well-defined syndrome, and data correlating androgen levels with specific signs or symptoms are unavailable. We recommend against the general use of T for the following indications: infertility; sexual dysfunction other than hypoactive sexual desire disorder; cognitive, cardiovascular, metabolic, or bone health; or general well-being. We recommend against the routine use of dehydroepiandrosterone due to limited data concerning its effectiveness and safety in normal women or those with adrenal insufficiency. We recommend against the routine prescription of T or dehydroepiandrosterone for the treatment of women with low androgen levels due to hypopituitarism, adrenal insufficiency, surgical menopause, pharmacological glucocorticoid administration, or other conditions associated with low androgen levels because there are limited data supporting improvement in signs and symptoms with therapy and no long-term studies of risk. Evidence supports the short-term efficacy and

  5. 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.

  6. Protein Arginine Methyltransferase 6 Involved in Germ Cell Viability during Spermatogenesis and Down-Regulated by the Androgen Receptor

    Directory of Open Access Journals (Sweden)

    Manling Luo

    2015-12-01

    Full Text Available Androgens and the androgen receptor (AR are of great importance to spermatogenesis and male fertility. AR knockout (ARKO mice display a complete insensitivity to androgens and male infertility; however, the exact molecular mechanism for this effect remains unclear. In this study, we found that the expression levels of Prmt6 mRNA and protein were significantly up-regulated in the testes of ARKO mice compared to wild type (WT mice. PRMT6 was principally localized to the nucleus of spermatogonia and spermatocytes by immunofluorescence staining. Furthermore, luciferase assay data showed that AR together with testosterone treatment suppressed Prmt6 transcription via binding to the androgen-responsive element (ARE of the Prmt6 promoter. Moreover, knockdown of Prmt6 suppressed germ cells migration and promoted apoptosis. In addition, both of these cellular activities could not be enhanced by testosterone treatment. Taken together, these data indicate that PRMT6, which was down-regulated by AR and influenced cell migration and apoptosis of germ cells, could play a potentially important role in spermatogenesis.

  7. Androgens in pregnancy: roles in parturition.

    Science.gov (United States)

    Makieva, Sofia; Saunders, Philippa T K; Norman, Jane E

    2014-01-01

    Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition. A review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility. Some, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens

  8. Androgen effects on women's gendered behaviour.

    Science.gov (United States)

    Udry, J R; Morris, N M; Kovenock, J

    1995-07-01

    Test of the applicability of the hormonal theory of sex-dimorphic behaviour to adult women is achieved in this study by assembling measures of prenatal and adult androgen exposure, and a broad measure of gendered behaviour on a sample of white women aged 27-30. Androgen exposure in the second (and no other) trimester of fetal life, combined with and in interaction with adult androgens, masculineses women's behaviour and explains a substantial proportion of the within-sex variance in women's adult gendered behaviour.

  9. 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.

  10. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Gao, Wenqing; Dalton, James T

    2007-03-01

    Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5alpha-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies.

  11. 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.

  12. ANABOLIC ANDROGENIC STEROIDS AND DEPENDENCE

    Directory of Open Access Journals (Sweden)

    IHSAN SARI

    2010-12-01

    Full Text Available Anabolic androgenic steroids are used for sportive, cosmetic, therapeutic and occupational reasons and there are many side effects reported (George, 2005; Nieminen et al., 1996; O'Sullivan et al., 2000. Prevalence of anabolic steroids’ use also indicates the importance of this topic. Moreover, it is now known that use of anabolic steroids could lead to dependence which could be psychological or/and physiological (Copeland et al., 2000. It isimportant to know about all aspects of anabolic steroids including dependence. Therefore, this study has attempted to give an insight into use of anabolic steroids and dependence. The discussion will focus on prevalence, reasons, and side effects of use and physiological and psychological dependence

  13. 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.

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

    Science.gov (United States)

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

    2013-04-01

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

  15. Anabolic-Androgenic Steroid Dependence: An Emerging Disorder

    Science.gov (United States)

    Kanayama, Gen; Brower, Kirk J.; Wood, Ruth I.; Hudson, James I.; Pope, Harrison G.

    2009-01-01

    Aims Anabolic-androgenic steroids (AAS) are widely used illicitly to gain muscle and lose body fat. Here we review the accumulating human and animal evidence showing that AAS may cause a distinct dependence syndrome, often associated with adverse psychiatric and medical effects. Method We present an illustrative case of AAS dependence, followed by a summary of the human and animal literature on this topic, based on publications known to us or obtained by searching the PubMed database. Results About 30% of AAS users appear to develop a dependence syndrome, characterized by chronic AAS use despite adverse effects on physical, psychosocial, or occupational functioning. AAS dependence shares many features with classical drug dependence. For example, hamsters will self-administer AAS, even to the point of death, and both humans and animals exhibit a well-documented AAS withdrawal syndrome, mediated by neuroendocrine and cortical neurotransmitter systems. AAS dependence may particularly involve opioidergic mechanisms. However, AAS differ from classical drugs in that they produce little immediate reward of acute intoxication, but instead a delayed effect of muscle gains. Thus standard diagnostic criteria for substance dependence, usually crafted for acutely intoxicating drugs, must be slightly adapted for cumulatively acting drugs such as AAS. Conclusions AAS dependence is a valid diagnostic entity, and likely a growing public health problem. AAS dependence may share brain mechanisms with other forms of substance dependence, especially opioid dependence. Future studies are needed to better characterize AAS dependence, identify risk factors for this syndrome, and develop treatment strategies. PMID:19922565

  16. Adrenal Androgens and the Menopausal Transition

    OpenAIRE

    Lasley, B. L.; Crawford, S.; McConnell, D.S.

    2011-01-01

    The concept that adrenal androgen production gradually declines with age has changed following the analysis of the longitudinal data collected in the Study of Women’s Health Across the Nation (SWAN). It is now recognized that four adrenal androgens (3-beta hydroxy-5-androsten-17-one or dehydroepiandrosterone--DHEA, its sulfate, dehydroepiandrosterone sulfate--DHEAS; androst-4-ene, 3,17-dione or androstenedione; and androst-5-ene-3-beta, 17-beta diol, also known as androstenediol or Adiol) ris...

  17. Androgen deprivation treatment of sexual behavior.

    Science.gov (United States)

    Houts, Frederick W; Taller, Inna; Tucker, Douglas E; Berlin, Fred S

    2011-01-01

    Gonadotropin-releasing hormone agonists are underutilized in patients seeking diminution of problematic sexual drives. This chapter reviews the literature on surgical castration of sex offenders, anti-androgen use and the rationale for providing androgen deprivation therapy, rather than selective serotonin reuptake inhibitors or more conservative interventions, for patients with paraphilias and excessive sexual drive. Discussions of informed consent, side effects, contraindications and case examples are provided. Copyright © 2011 S. Karger AG, Basel.

  18. 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.

  19. Sarcopenia and Androgens: A Link between Pathology and Treatment

    Science.gov (United States)

    Basualto-Alarcón, Carla; Varela, Diego; Duran, Javier; Maass, Rodrigo; Estrada, Manuel

    2014-01-01

    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. PMID:25566189

  20. Punishment insensitivity and impaired reinforcement learning in preschoolers

    Science.gov (United States)

    Briggs-Gowan, Margaret J.; Nichols, Sara R.; Voss, Joel; Zobel, Elvira; Carter, Alice S.; McCarthy, Kimberly J.; Pine, Daniel S.; Blair, James; Wakschlag, Lauren S.

    2013-01-01

    Background Youth and adults with psychopathic traits display disrupted reinforcement learning. Advances in measurement now enable examination of this association in preschoolers. The current study examines relations between reinforcement learning in preschoolers and parent ratings of reduced responsiveness to socialization, conceptualized as a developmental vulnerability to psychopathic traits. Methods 157 preschoolers (mean age 4.7 ±0.8 years) participated in a substudy that was embedded within a larger project. Children completed the “Stars-in-Jars” task, which involved learning to select rewarded jars and avoid punished jars. Maternal report of responsiveness to socialization was assessed with the Punishment Insensitivity and Low Concern for Others scales of the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB). Results Punishment Insensitivity, but not Low Concern for Others, was significantly associated with reinforcement learning in multivariate models that accounted for age and sex. Specifically, higher Punishment Insensitivity was associated with significantly lower overall performance and more errors on punished trials (“passive avoidance”). Conclusions Impairments in reinforcement learning manifest in preschoolers who are high in maternal ratings of Punishment Insensitivity. If replicated, these findings may help to pinpoint the neurodevelopmental antecedents of psychopathic tendencies and suggest novel intervention targets beginning in early childhood. PMID:24033313

  1. 2007 Insensitive Munitions and Energetic Materials Technology Symposium

    Science.gov (United States)

    2007-10-18

    cheap melt-cast compositions will ever be truly IM? – The need to agree internationally a ‘smart’ set of tests to ensure that only genuine low...of Insensitive Munitions and Their Estimated Contribution to CV Safety", CRM 90-260 / March 1991 Enterprise Nimitz 44 40.4106 74 141 825.3 28 323

  2. 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...... functionality and reasonable performance are readily designed...

  3. 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 ...

  4. 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.

  5. Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Vindrieux David

    2011-12-01

    Full Text Available Abstract Background Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. Results In contrast to androgen-insensitive PC3 cells, decoy (DcR2 and death (DR5 receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. Conclusions The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

  6. 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

  7. Metabolic sequelae associated with androgen deprivation therapy for prostate cancer.

    Science.gov (United States)

    Faris, Jason E; Smith, Matthew R

    2010-06-01

    To summarize the metabolic alterations associated with androgen deprivation therapy (ADT) for prostate cancer and to evaluate the evidence linking ADT with an increased risk of diabetes and cardiovascular disease. ADT by either bilateral orchiectomy or treatment with gonadotropin-releasing hormone agonists causes changes in body composition, alterations in lipid profiles, and decreased insulin sensitivity. The spectrum of metabolic changes during ADT is distinct from classically described metabolic syndrome. Population-based, linked cancer registry studies have consistently reported significant associations between ADT and greater risk for diabetes mellitus. Some but not all studies have reported a link between ADT and cardiovascular disease risk. Most studies have reported no increase in cardiovascular mortality following ADT. ADT appears causally associated with diabetes mellitus. ADT is also linked to cardiovascular morbidity, although there is less evidence that this relationship is causal.

  8. 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.

  9. 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....

  10. Salbutamol exhibits androgenic activity in vitro

    Science.gov (United States)

    von Bueren, André O; Ma, Risheng; Schlumpf, Margret; Lichtensteiger, Walter

    2007-01-01

    Background Salbutamol has been shown to mediate anabolic effects after intravenous administration. However, the mechanism responsible for the anabolic actions of salbutamol remains unknown. Aim To investigate the potential mechanism by which salbutamol mediates anabolic effects in vitro. Methods The potential androgenic activity of salbutamol was investigated in vitro by the A‐Screen assay that measures androgen‐dependent inhibition of proliferation of the androgen receptor (AR)‐positive human mammary carcinoma cell line, MCF7‐AR1. Results The assay was validated with three known androgens; methyltrienolone (R1881), 5α‐dihydrotestosterone (DHT) and danazol. IC50 values of R1881, DHT and danazol, 4.41×10–11, 4.44×10−11 and 1.08×10−8 M, respectively, were in the ranges known from earlier studies. Our results demonstrate that salbutamol exhibits androgenic activity, with an IC50 value of 8.93×10−6 M. Anti‐estrogenic or cytotoxic effects, which might have interfered with the assay, were excluded by additional experiments on wild‐type MCF7 and MCF7‐AR1 cells, respectively. Conclusion These data indicate that salbutamol exerts anabolic effects through androgen receptor agonistic activity in vitro. PMID:17510230

  11. 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.

  12. Integrated Experiment and Modeling of Insensitive High Explosives

    Science.gov (United States)

    Stewart, D. Scott; Lambert, David E.; Yoo, Sunhee; Lieber, Mark; Holman, Steven

    2009-12-01

    New design paradigms for insensitive high explosives are being sought for use in munitions applications that require enhanced safety, reliability and performance. We describe recent work of our group that uses an integrated approach to develop predictive models, guided by experiments. Insensitive explosive can have relatively longer detonation reaction zones and slower reaction rates than their sensitive counterparts. We employ reactive flow models that are constrained by detonation shock dynamics (DSD) to pose candidate predictive models. We discuss the variation of the pressure dependent reaction rate exponent and reaction order on the length of the supporting reaction zone, the detonation velocity curvature relation, the computed critical energy required for initiation, the relation between the diameter effect curve and the corresponding normal detonation velocity curvature relation.

  13. Discovery AND Therapeutic Promise OF Selective Androgen Receptor Modulators

    Science.gov (United States)

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

    2007-01-01

    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. PMID:15994457

  14. 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...

  15. Tradeoff methods in multiobjective insensitive design of airplane control systems

    Science.gov (United States)

    Schy, A. A.; Giesy, D. P.

    1984-01-01

    The latest results of an ongoing study of computer-aided design of airplane control systems are given. Constrained minimization algorithms are used, with the design objectives in the constraint vector. The concept of Pareto optimiality is briefly reviewed. It is shown how an experienced designer can use it to find designs which are well-balanced in all objectives. Then the problem of finding designs which are insensitive to uncertainty in system parameters are discussed, introducing a probabilistic vector definition of sensitivity which is consistent with the deterministic Pareto optimal problem. Insensitivity is important in any practical design, but it is particularly important in the design of feedback control systems, since it is considered to be the most important distinctive property of feedback control. Methods of tradeoff between deterministic and stochastic-insensitive (SI) design are described, and tradeoff design results are presented for the example of the a Shuttle lateral stability augmentation system. This example is used because careful studies have been made of the uncertainty in Shuttle aerodynamics. Finally, since accurate statistics of uncertain parameters are usually not available, the effects of crude statistical models on SI designs are examined.

  16. Bioactive Androgens and Glucuronidated Androgen Metabolites are Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity among Older Black Men

    OpenAIRE

    Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S; Gordon, Christopher L; Goodpaster, Bret H; Kuller, Lewis H; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Orwoll, Eric S; Zmuda, Joseph M

    2011-01-01

    Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T...

  17. 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.

  18. Adrenal androgens and the menopausal transition.

    Science.gov (United States)

    Lasley, Bill L; Crawford, Sybil; McConnell, Daniel S

    2011-09-01

    The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.

  19. 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

  20. 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.

  1. Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide.

    Science.gov (United States)

    Hoefer, Julia; Akbor, Mohammady; Handle, Florian; Ofer, Philipp; Puhr, Martin; Parson, Walther; Culig, Zoran; Klocker, Helmut; Heidegger, Isabel

    2016-09-13

    Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such resistances are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress wild-type AR, as well as a cell which has been adapted to long term androgen ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of cultivation, sustained growth in the presence of enzalutamide was achieved. When compared to controls, resistant cells exhibit significantly decreased sensitivity to enzalutamide as measured with 3[H]thymidine incorporation and WST assay. Moreover, these cell models exhibit partly re-activated AR signaling despite presence of enzalutamide. In addition, we show that enzalutamide resistant cells are insensitive to bicalutamide but retain considerable sensitivity to abiraterone. Mechanistically, enzalutamide resistance was accompanied by increased AR and AR-V7 mRNA and protein expression as well as AR gene amplification, while no additional AR mutations have been identified.

  2. Mathematical Models of Androgen Resistance in Prostate Cancer Patients under Intermittent Androgen Suppression Therapy

    Directory of Open Access Journals (Sweden)

    Javier Baez

    2016-11-01

    Full Text Available Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA. We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT. While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction.

  3. 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.

  4. Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Alexandra M Fajardo

    Full Text Available Tocopherylquinone (TQ, the oxidation product of alpha-tocopherol (AT, is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells, whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zheng [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China); Jin, Bo [Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034 (China); Jin, Yaqiong [Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children' s Hospital, Capital Medical University, Beijing 100045 (China); Huang, Shengquan; Niu, Xiaohua [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China); Mao, Zebin [The Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Xin, Dianqi, E-mail: xin-dianqi@163.com [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China)

    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.

  6. Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation.

    Science.gov (United States)

    Fietz, D; Markmann, M; Lang, D; Konrad, L; Geyer, J; Kliesch, S; Chakraborty, T; Hossain, H; Bergmann, M

    2015-12-29

    Androgens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell culture systems and AR-transfected cell lines are needed. Transfection of AR into cell lines and subsequent gene expression analysis after androgen treatment is well established to investigate the molecular biology of target cells. However, it remains unclear how the transfection with AR itself can modulate the gene expression even without androgen stimulation. Therefore, we transfected Ar-deficient rat Sertoli cells 93RS2 by electroporation using a full length human AR. Transfection success was confirmed by Western Blotting, immunofluorescence and RT-PCR. AR transfection-related gene expression alterations were detected with microarray-based genome-wide expression profiling of transfected and non-transfected 93RS2 cells without androgen stimulation. Microarray analysis revealed 672 differentially regulated genes with 200 up- and 472 down-regulated genes. These genes could be assigned to four major biological categories (development, hormone response, immune response and metabolism). Microarray results were confirmed by quantitative RT-PCR analysis for 22 candidate genes. We conclude from our data, that the transfection of Ar-deficient Sertoli cells with AR has a measurable effect on gene expression even without androgen stimulation and cause Sertoli cell damage. Studies using AR-transfected cells, subsequently stimulated, should consider alterations in AR-dependent gene expression as off-target effects of the AR transfection itself.

  7. Nonsteroidal mycotoxin alternariol is a full androgen agonist in the yeast reporter androgen bioassay.

    Science.gov (United States)

    Stypuła-Trębas, Sylwia; Minta, Maria; Radko, Lidia; Jedziniak, Piotr; Posyniak, Andrzej

    2017-10-01

    Alternariol (AOH) is a toxic metabolite of phytopathogenic fungi of the Alternaria spp. and important contaminant of agricultural commodities. According to the recent studies, AOH has a potential to modulate the endocrine system of humans and animals. In the view of these reports, our study addressed the effects of AOH on human estrogen receptor (hERα) and androgen receptor (hAR) signaling with the use of the yeast estrogen and androgen reporter bioassays. Our results show that, apart from a weak estrogenic response, AOH induces full androgenic response of the bioassay with the EC50 of 269.4μM. The androgenic potency of AOH relative to testosterone (T) is 0.046%. Moreover, in the presence of T, AOH at 5μM acts as a weak antiandrogen, whereas at higher concentrations AOH sum up with the androgenic activity of T in a dose-dependent manner, suggesting additive effect. To our knowledge it is the first report of the androgenic potency of natural, nonsteroidal substance and may have the impact on the direction of the further studies. Further research is warranted to clarify the role of AOH in disruption of AR signaling in humans and animals. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 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.

  9. 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

  10. 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 ...

  11. Leverpatologi associeret med anaboliske-androgene steroider

    DEFF Research Database (Denmark)

    Søe, Katrine; Søe, Martin Jensen; Gluud, C N

    1994-01-01

    This review regards the liver damaging side-effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved...

  12. Development of selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Narayanan, Ramesh; Coss, Christopher C; Dalton, James T

    2017-06-15

    The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Deciphering the selective androgen receptor modulators paradigm.

    Science.gov (United States)

    Zhang, Xuqing; Sui, Zhihua

    2013-02-01

    The development and potential clinical use of tissue-selective androgen receptor modulators (SARMs) have advanced tremendously over the past few years. A key aspect of SARMs is the ability to clearly differentiate between the anabolic and androgenic activities. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands. This paper also provides an update on SARM discovery paradigms for preclinical evaluations. Promising results have been obtained in preclinical investigations and initial clinical trials, but long-term safety, tolerability and efficacy studies in patients are still necessary. Preclinically, improving knowledge of tissue selectivity at the molecular level, developing AR selectivity transcription profile, exploring in vitro/in vivo correlation, along with expanding selectivity evaluation among more androgen responsive tissues would accelerate the discovery of a new generation of more selective and safer clinical candidates, minimize false leads and hasten development of effective approaches for an expanded range of clinical conditions.

  14. The reciprocal links between synaptophysin serum levels and the prevalence of metabolic syndrome according to selected low-grade inflammation indices and age-related androgen serum level changes in men.

    Science.gov (United States)

    Herman, Waldemar Adam; Wójcicka, Marlena; Kołodziejczak, Barbara; Losy, Jacek; Łącka, Katarzyna

    2016-01-01

    The correlations between synaptophysin (SYP) plasma levels and the brain neurotransmission activity are still not strictly identified. However, the efficiency of neurotransmission depends, inter alia, on the age, hormonal status, and coexistence of a low-grade systemic inflammation (LGSI) which is regarded as a pathogenic link with obesity and insulin resistance, atherogenesis and aging per se. The aim of this study was to investigate the associations between synaptophysin serum levels and age, LGSI indices, homocysteine and selected hormonal parameters (dehydroepiandrosterone and its sulfate, free-testosterone, SHBG) and the prevalence of metabolic syndrome (MS) in men over the age of 40. After randomization, 157 male volunteers aged 40-80 years were included in a retrospective study. MS was diagnosed according to the International Diabetes Federation criteria. For the diagnosis of late-onset hypogonadism (LOH) we adopted the criteria proposed by the European Male Aging Study (EMAS). Synaptophysin plasma concentrations in respondents decreased with age, but only between the ages of 40 to 70 years. There were no differences in SYP plasma concentrations in men suffering from MS compared to healthy subjects (p=0.845). Men suffering from MS demonstrated while higher hs-CRP (high sensitive C - reactive protein) levels than healthy (p=0.019), contrary to the α1-antichymotrypsin and transferrin. A positive monotonic correlation between synaptophysin and hs-CRP was demonstrated (r=0.235; p=0.003). No statistically significant relationships between SYP and homocysteine plasma levels were presented (r=0.047; p=0.562), although in men diagnosed with MS higher homocysteine levels compared to healthy subjects were demonstrated. No correlations between synaptophysin and free testosterone (r=-0.036; p=0.651), DHEA (r=-0.122; p=0.128) and its sulphate (r=-0.024; p=0.764) as well as SHBG (r=-0.088; p=0.288) were demonstrated. Although the correlations between synaptophysin plasma

  15. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

    Science.gov (United States)

    Pasquali, R; Gambineri, A; Biscotti, D; Vicennati, V; Gagliardi, L; Colitta, D; Fiorini, S; Cognigni, G E; Filicori, M; Morselli-Labate, A M

    2000-08-01

    Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was

  16. 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.

  17. Androgen regulation of prostate cancer: where are we now?

    Science.gov (United States)

    Corona, G; Baldi, E; Maggi, M

    2011-03-01

    Androgens play an essential role in the development and differentiation of the prostate gland; their contribution to pathological conditions, such as benign prostatic hyperplasia and prostate cancer (PC), remains unclear. We reviewed relationships between androgens and the prostate both in physiological and pathological conditions. A systematic search of published evidence was performed using Medline (1969 to September 2010). Androgen-dependency of prostate growth is evident only in the hypogonadal condition, but not in the eugonadal state (the "saturation hypothesis"). There is unequivocal evidence that reducing androgen signaling to the hypogonadal range can reduce PC growth and patient symptoms. At physiological testosterone concentration there is no link between androgen levels and PC risk. In addition, different strategies of androgen deprivation (ADT) for advanced PC are only palliative and rarely cure patients. Preliminary evidence indicates that a low androgen milieu is associated with tumor aggressiveness. Transition to androgen-independence is complex and involves both selection and outgrowth of preexisting androgen resistant clones, as well as adaptative upregulation of genes that help the cancer cells to survive and grow after ADT. Because androgens are essential for the regulation of fat distribution, insulin sensitivity, and lipid and bone metabolism, recent publications have highlighted the concept that ADT may also be involved with an increase in overall, as well as cardiovascular, morbidity and mortality. While ADT still represents a cornerstone for the palliative therapy of a small fraction of aggressive PC, a "misuse and/or abuse" of ADT should be avoided.

  18. Specific modulation of nongenomic androgen signaling in the ovary.

    Science.gov (United States)

    White, Stacy N; Jamnongjit, Michelle; Gill, Arvind; Lutz, Lindsey B; Hammes, Stephen R

    2005-01-01

    Maturation, or meiotic progression, of amphibian oocytes is one of the few physiologically relevant steroid-mediated processes that occurs in the complete absence of transcription from beginning to end. As such, frog oocyte maturation has served as a useful model of nongenomic steroid signaling for many years. Earlier work in Xenopus laevis demonstrated that, although several steroids promoted oocyte maturation in vitro, androgens were the most abundant and potent steroids detected in the serum and ovaries of ovulating frogs. Thus, androgens were likely the primary physiologic regulators of Xenopus oocyte maturation, mediating their actions at least in part via classical androgen receptors expressed in oocytes. The importance of androgens for Xenopus oocyte maturation and ovulation has now been confirmed, as inhibition of androgen production in vivo by blocking CYP17 activity reduced hCG-triggered oocyte maturation and delayed ovulation in female frogs. Taking advantage of the absolute transcription-independence of this androgen-mediated response, selective androgen receptor modulators (SARMs) have been characterized that specifically promote genomic versus nongenomic androgen responses. These include androstenediol and estren, which preferentially promote nongenomic signals, as well as R1881 and 19-nortestosterone, which preferentially promote genomic signaling. Interestingly, the SARMs androstenediol and R1881 signal similarly in mouse oocytes, demonstrating the conserved nature of androgen-mediated maturation in vertebrates. These results suggest that SARMs may serve as useful tools for specifically regulating nongenomic androgen signaling both in vitro and in vivo.

  19. Inhibition of the RANK/RANKL signaling with osteoprotegerin prevents castration-induced acceleration of bone metastasis in castration-insensitive prostate cancer.

    Science.gov (United States)

    Takayama, Koichiro; Inoue, Takamitsu; Narita, Shintaro; Maita, Shinya; Huang, Mingguo; Numakura, Kazuyuki; Tsuruta, Hiroshi; Saito, Mitsuru; Maeno, Atsushi; Satoh, Shigeru; Tsuchiya, Norihiko; Habuchi, Tomonori

    2017-07-01

    Androgen deprivation therapy (ADT) for patients with metastatic or locally advanced prostate cancer reduces bone mineral density by stimulating receptor activator of nuclear factor kappa-B (RANK) signaling in osteoclasts. The involvement of the RANK/RANKL signaling in ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer was examined in a murine model using osteoprotegerin (OPG). Male Balb/c nude mice were divided into three groups: the non-castration, castration, and castration + OPG groups. PC-3M-luc-C6 was injected into the left ventricle of the mice. Recombinant OPG was injected intravenously twice weekly in the castration + OPG group. In-vivo imaging system (IVIS ® ) determined that the prevalence and photon counts of bone metastasis in the castration group were significantly higher than that in the non-castration and castration + OPG groups. The mean number of RANKL-positive osteoblasts and the mean serum RANKL level in the castration group were significantly higher than those in the non-castration group. RANKL-enhanced activation of osteoclasts was attenuated in the castration + OPG group. These results suggest that the mechanisms of RANK/RANKL signaling are involved in the ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Wang Y-K, Charng M-J, Ueng Y-F. Determination of serum atorvastatin concentrations in lipid-controlling patients with and without myalgia syndrome ...specific antigen levels: analysis of the National Health and Nutrition Examination Survey. Journal of clinical oncology : official journal of the...in prostate cancer. Curr Opin Oncol 24:251-7, 2012 6. Mostaghel EA, Nelson PS: Intracrine androgen metabolism in prostate cancer progression

  1. Clinical Usefulness of Chlormadinone Acetate as an Alternative Antiandrogen Therapy for Prostate Cancer Relapse after Combined Androgen Blockade Therapy

    OpenAIRE

    江原, 英俊; 加藤, 成一; 中根, 慶太; 加藤, 卓; 高田, 俊彦; 小島, 圭太郎; 亀井, 信吾; 萩原, 徳康; 柚原, 一哉; 高橋, 義人; 藤本, 佳則; 藤広, 茂; 蟹本, 雄右; 出口, 隆

    2009-01-01

    We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we ad...

  2. 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

  3. 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).

  4. 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

  5. Androgen deprivation therapy-associated vasomotor symptoms

    OpenAIRE

    Jones, Jason M; Kohli, Manish; Loprinzi, Charles L

    2012-01-01

    Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hor...

  6. 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....

  7. Ultra-wideband polarization insensitive UT-shaped metamaterial absorber

    Science.gov (United States)

    Karampour, Nasrollah; Nozhat, Najmeh

    2017-05-01

    In this paper, an ultra-wideband metamaterial absorber (MMA) with U and T shaped resonators has been proposed. The resonators and the ground plane consist of gold (Au) and titanium (Ti) layers. The resistive sheet effect of Ti layer and the resonance elements in the structure cause a broad absorption spectrum. The simulations are based on the finite element method (FEM) and the results show that the absorption of the proposed structure is more than 90% between 150 and 300 THz that is much larger than previous works. Moreover, by applying the interference theory, we have demonstrated that the simulation results are in good agreement with the theoretical results. The primary proposed MMA is polarization sensitive. Therefore, a polarization insensitive metamaterial absorber has been suggested. Also, because of the extra resonance elements the full width at 90% absorption increases about 35 THz. This ultra-wideband MMA has various applications in microbalometer, imaging, thermal emitters, photovoltaic, and energy harvesting.

  8. Design of graphene-based polarization-insensitive optical modulator

    Directory of Open Access Journals (Sweden)

    Hu Xiao

    2018-02-01

    Full Text Available By exploiting the electroabsorption effect of graphene, we present a graphene-based polarization-insensitive optical modulator. The waveguide structure consists of a silica substrate, high-index silicon strip waveguide, Si3N4 dielectric spacer, two graphene layers, and two metal electrodes. The modulator performance is comprehensively studied in terms of attenuation, insertion loss, modulation depth, and bandwidth. We achieve broadband >16 dB attenuation graphene-based optical modulator over a 35 nm wavelength range (covering C band with an imbalance of no >1 dB and insertion loss of <2 dB for transverse magnetic and transverse electric polarized modes. Moreover, the electrical properties such as energy per bit consumption (Ebit are also studied.

  9. Mechanisms of glucocorticoid action and insensitivity in airways disease.

    Science.gov (United States)

    Boardman, C; Chachi, L; Gavrila, A; Keenan, C R; Perry, M M; Xia, Y C; Meurs, H; Sharma, P

    2014-12-01

    Glucocorticoids are the mainstay for the treatment of chronic inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, it has been recognized that glucocorticoids do not work well in certain patient populations suggesting reduced sensitivity. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Studies are emerging to understand these mechanisms in detail, which would help in increasing glucocorticoid sensitivity in patients with chronic airways disease. This review aims to highlight both classical and emerging concepts of the anti-inflammatory mechanisms of glucocorticoids and also review some novel strategies to overcome steroid insensitivity in airways disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. Analytical Methods for Detonation Residues of Insensitive Munitions

    Science.gov (United States)

    Walsh, Marianne E.

    2016-01-01

    Analytical methods are described for the analysis of post-detonation residues from insensitive munitions. Standard methods were verified or modified to obtain the mass of residues deposited per round. In addition, a rapid chromatographic separation was developed and used to measure the mass of NTO (3-nitro-1,2,4-triazol-5-one), NQ (nitroguanidine) and DNAN (2,4-dinitroanisole). The HILIC (hydrophilic-interaction chromatography) separation described here uses a trifunctionally-bonded amide phase to retain the polar analytes. The eluent is 75/25 v/v acetonitrile/water acidified with acetic acid, which is also suitable for LC/MS applications. Analytical runtime was three minutes. Solid phase extraction and LC/MS conditions are also described.

  12. Evaluation of ingredients for the development of new insensitive munitions.

    Energy Technology Data Exchange (ETDEWEB)

    Maharrey, Sean P.; Johnston, Lois A.; Behrens, Richard, Jr.; Wiese-Smith, Deneille

    2004-12-01

    Several ingredients being considered by the U.S. Army for the development of new insensitive munitions have been examined. One set of ingredients consists of 2,4-dinitrophenylhydrazine (DNPH) and hexahydro-1,3,5-trinitro-s-triazine (RDX). In this set, the decomposition of the mixture was examined to determine whether adding DNPH to RDX would generate a sufficient quantity of gas to rupture the case of a munition prior to the onset of the rapid reaction of RDX, thus mitigating the violence of reaction. The second set of ingredients consists of three different reduced sensitivity RDX (RS-RDX) powders manufactured by SNPE and Dyno-Nobel. In this set, the objective was to determine properties of RS-RDX powders that may distinguish them from normal RDX powder and may account for their reduced shock sensitivity. The decomposition reactions and sublimation properties of these materials were examined using two unique instruments: the simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) instrument and the Fourier Transform ion cyclotron resonance (FTICR) mass spectrometry instrument. These instruments provide the capability to examine the details of decomposition reactions in energetic materials. DNPH does not appear to be a good candidate to mitigate the violence of the RDX reaction in a munition. DNPH decomposes between 170 C and 180 C. When mixed with RDX it decomposes between 155 C and 170 C. It decomposes to form 1,3-dintrobenzene (DNB), ammonia, water and nitrogen. Of these compounds only nitrogen and ammonia are capable of generating high pressures within a munition. When DNPH is mixed with RDX, the DNB formed in the decomposition of DNPH interacts with RDX on the surface of the RDX powder leading to a higher rate of formation of CH2O and N2O. The CH2O is consumed by reaction with DNPH to form 2-methylene-1-(2,4-dintrophenyl)hydrazine. As a result, DNPH does not generate a large quantity of gas that will lead to rupture of a munition case. Another

  13. Application of composite materials to impact-insensitive munitions

    Science.gov (United States)

    Neradka, Vincent F.; Chang, Yale; Grady, Joseph E.; Trowbridge, Daniel A.

    1992-01-01

    An approach is outlined for developing bullet-impact-insensitive munitions based on composite materials that provide rapid venting of the rocket-motor case. Impact experiments are conducted with test specimens of hybrid laminates of graphite/epoxy and epoxy reinforcing with woven glass fibers. The dynamic strain response and initial impact force are measured with strain gauges, and perforation damage is examined in the plates. The results show that impact damage can be designed by means of parametric variations of the fiber, matrix, and ply orientations. It is suggested that rocket-motor cases can be designed with composite materials to provide rapid venting during the failure mode. The experimental ballistic testing performed provides data that can be used comparatively with analytical data on composite materials.

  14. Recurrent angioedema associated with hypogonadism or anti-androgen therapy.

    Science.gov (United States)

    Pichler, W J; Lehner, R; Späth, P J

    1989-10-01

    Two male patients with hypogonadism and four female patients who received an anti-androgen as contraceptive (cyproteronacetate) and who had recurrent angioedema are described. In one male patient, augmentation of the plasma androgen level resulted in disappearance of symptoms. In the four female patients, recurrent angioedema and urticaria developed after initiation of the anti-androgen treatment. Cessation of cyproteronacetate and a change to another contraceptive resulted in complete resolution of the previously frequent angioedematous attacks. The women are still symptom free after more than 60 patient's months. These cases suggest that an androgen deficit due to either hypogonadism or to anti-androgen treatment may be another cause of angioedema. One of the two male patients was untreated and presented with 40% normal value of C1-INH. Androgen therapy normalized C1-INH concentration in this male patient. Functional C1-INH in the same patient, studied before and after the beginning of androgen therapy, clearly increased when assessed by inhibition of amidolytic activity of C1-esterase. The other male patient with hypogonadism had already been under androgen treatment for 4 years and had C1-INH levels in the normal range. In the female patients, complement profiles were normal before and after cessation of anti-androgen contraception; however, the C1-INH plasma levels were higher after cessation of anti-androgen anticonception. These results indicate an effect of androgen deficit on the level of C1-INH in circulating plasma but do not prove a role of C1-INH in angioedema associated with diminished androgen plasma levels.

  15. Prostate cancer: molecular biology of early progression to androgen independence.

    Science.gov (United States)

    Sadar, M D; Hussain, M; Bruchovsky, N

    1999-12-01

    To improve the therapy for prostate cancer, it will be necessary to address the problems of progression to androgen independence and the process of metastatic spread of tumour. The complexity of the latter condition is likely to mitigate against the immediate development of relevant therapeutic approaches. However, the basis of androgen independence appears to be a problem of simpler dimensions and more amenable to treatment with current therapeutic technology. Since early tumour progression can be detected by an incomplete prostate-specific antigen (PSA) response to androgen withdrawal therapy, a study of the molecular biology of PSA gene regulation may well provide insight into new methods for preventing or delaying this problem. Mounting evidence suggests that ligand-independent activation of the androgen receptor may be one underlying mechanism of androgen independence. In the absence of androgen, a compensatory increase in the activity of cAMP-dependent protein kinase (PKA) enhances the ability of the androgen receptor to bind to the response elements regulating PSA gene expression. The activation of the androgen receptor through up-regulation of the PKA signal transduction pathway involves the amino-terminus of the androgen receptor, the function of which may be altered either by modifications such as phosphorylation, or through interactions with co-regulators or other proteins. Of therapeutic interest is the fact that this effect can be counteracted experimentally by the anti-androgen, bicalutamide, and clinically by several other similar agents. We speculate that the inhibition of PKA-activated androgen receptor might also be accomplished by decoy molecules that can bind to the relevant activated site on the amino-terminus or competitively interact with proteins recruited by the PKA pathway that are responsible for activating the receptor in the absence of androgen. Such molecules might include small mimetic substances or agents that can gain access to the

  16. Pathological changes in anabolic androgenic steroid users.

    Science.gov (United States)

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  17. Androgen therapy in women, beyond libido.

    Science.gov (United States)

    Davis, S R

    2013-08-01

    The aim of this review was to summarize the literature regarding the potential role of testosterone therapy for women. The author conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2013) for English-language studies that included the following search terms: 'testosterone' or 'androgen' combined with 'women', 'therapy' or 'treatment'. Randomized, placebo-controlled trials have consistently shown that transdermal testosterone therapy improves sexual desire, arousal, orgasm frequency and satisfaction in premenopausal and postmenopausal women presenting with sexual desire/arousal problems. No adverse metabolic effects have been observed in these studies. In postmenopausal women, testosterone therapy has also been associated with favorable effects on body composition, bone, cardiovascular function and cognitive performance. Although androgens have many varied roles, the focus of testosterone therapy for women has been on improving sexual desire. Not only do testosterone effects on sexuality extend beyond libido, but testosterone has other key physiological actions. Issues that urgently need to be addressed include approval of a testosterone formulation that delivers a female dose such that physicians refrain from prescribing compounded testosterone or modifying doses of testosterone formulated for men and regulation of prescription of compounded androgens for women.

  18. Modulators of androgen and estrogen receptor activity.

    Science.gov (United States)

    Clarke, Bart L; Khosla, Sundeep

    2010-01-01

    This review focuses on significant recent findings regarding modulators of androgen and estrogen receptor activity. Selective androgen receptor modulators (SARMs) interact with androgen receptors (ARs), and selective estrogen receptor modulators (SERMs) interact with estrogen receptors (ERs), with variable tissue selectivity. SERMs, which interact with both ERб and ERв in a tissue-specific manner to produce diverse outcomes in multiple tissues, continue to generate significant interest for clinical application. Development of SARMs for clinical application has been slower to date because of potential adverse effects, but these diverse compounds continue to be investigated for use in disorders in which modulation of the AR is important. SARMs have been investigated mostly at the basic and preclinical level to date, with few human clinical trials published. These compounds have been evaluated mostly for application in different stages of prostate cancer to date, but they hold promise for multiple other applications. Publication of the large STAR and RUTH clinical trials demonstrated that the SERMs tamoxifen and raloxifene have interesting similarities and differences in tissues that contain ERs. Lasofoxifene, bazedoxifene, and arzoxifene are newer SERMs that have been demonstrated in clinical trials to more potently increase bone mineral density and lower serum cholesterol values than tamoxifen or raloxifene. Both SARMs and SERMs hold great promise for therapeutic use in multiple disorders in which tissue-specific effects are mediated by their respective receptors.

  19. 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...

  20. 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.

  1. 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.

  2. The development of an autonomous gust insensitive unmanned aerial vehicle

    Science.gov (United States)

    Pisano, William James

    The study of a small Unmanned Aerial Vehicle (UAV) that is designed towards eventual operation in harsh storm-like conditions is presented. Investigation of the aircraft equations of motion shows that the selection of certain aerodynamic derivatives has a significant effect on the gust response of a small unmanned aircraft. Analytical comparison of this newly formulated Autonomous Gust Insensitive Aircraft (AGIA) to a conventionally designed aircraft shows a significant reduction in undesirable roll motion caused by gusts. A simulation is presented showing that the AGIA is capable of operating in more extreme environments than a conventional aircraft, and puts less strain on the control system components in both extreme and calm environments. The role that aircraft size plays in gust response is also studied. Pilot instinct dictates that smaller aircraft are more difficult to fly in windy environments than larger ones. This phenomenon is investigated using an analytic approach, providing insight into why smaller aircraft are indeed more difficult to fly in more challenging environments. As an aircraft gets smaller, its natural aerodynamic modes and response get faster. In an ideal system, this does not limit small aircraft to poor performance (in fact it will be shown that idealized small aircraft theoretically perform better than their larger counterparts). A more realistic system is presented that includes not only aerodynamics, but also realistic sensor and actuator dynamics. It is shown that these additional dynamics become a limiting factor in control system performance, and thus limit the closed-loop flight performance of small aircraft in turbulent environments. It is shown that the AGIA design approach plays a more significant role the as an aircraft gets smaller. To provide experimental validation of the gust insensitive theory presented herein, a representative small conventional aircraft was built alongside a similar aircraft that incorporated the AGIA

  3. 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.

  4. Additive effects of dietary glycotoxins and androgen excess on the ...

    African Journals Online (AJOL)

    AGE immunoreactivity was higher on the renal tubules of the androgenized animals fed with HA diet, when compared with the animals fed with LA diet, but did not significantly differ among the two groups. Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen ...

  5. 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....

  6. 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 ...

  7. 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.

  8. Viable supersymmetric model with UV insensitive anomaly mediation

    Science.gov (United States)

    Ibe, Masahiro; Kitano, Ryuichiro; Murayama, Hitoshi

    2005-04-01

    We propose an electroweak model which is compatible with the UV insensitive anomaly-mediated supersymmetry breaking. The model is an extension of the next to minimal supersymmetric standard model (NMSSM) by adding vectorlike matter fields which can drive the soft scalar masses of the singlet Higgs field negative and the successful electroweak symmetry breaking is achieved. Viable parameter regions are found to preserve perturbativity of all the coupling constants up to the Planck scale. With this success, the model becomes a perfect candidate of physics beyond the standard model without the flavor changing neutral current and CP problem. The cosmology is also quite interesting. The lightest neutralino is the wino which is a perfect cold dark matter candidate assuming the nonthermal production from the gravitino decay. There is no gravitino problem because it decays before the big-bang nucleosynthesis era, and thus the thermal leptogenesis works. The cosmological domain wall problem inherent in the NMSSM is absent since the Z3 symmetry is broken by the QCD instanton effect in the presence of the vectorlike quarks. We also briefly comment on a possible solution to the strong CP problem à la the Nelson-Barr mechanism.

  9. Demonstration of a reversible phase-insensitive optical amplifier

    Science.gov (United States)

    Yoshikawa, Jun-Ichi; Miwa, Yoshichika; Filip, Radim; Furusawa, Akira

    2011-05-01

    We experimentally demonstrate phase-insensitive linear amplification of a continuous variable system in the optical regime, preserving the ancilla system at the output. Since our amplification operation is unitary up to small excess noise, it is reversible beyond the classical limit. Here, entanglement between the amplified output system and the ancilla system is the resource for the reversibility, and the amplification gain is G=2.0. In addition, combining this amplifier with a beamsplitter, we also demonstrate approximate cloning of coherent states where an anticlone is present. We investigate the reversibility by reconstructing the initial state from the output correlations, and the results are slightly beyond the cloning limit. Furthermore, full characterization of the amplifier and cloner is given by using coherent states with several different mean values as inputs. Our amplifier is based on linear optics, offline-prepared additional ancillas in nonclassical states, and homodyne measurements followed by feedforward. Squeezed states are used as the additional ancillas, and nonlinear optical effects are exploited only for their generation. They introduce nonclassicality into the amplifying operation, making entanglement at the output.

  10. Temperature insensitive curvature sensor based on cascading photonic crystal fiber

    Science.gov (United States)

    Fu, Guangwei; Li, Yunpu; Fu, Xinghu; Jin, Wa; Bi, Weihong

    2018-03-01

    A temperature insensitive curvature sensor is proposed based on cascading photonic crystal fiber. Using the arc fusion splicing method, this sensor is fabricated by cascading together a single-mode fiber (SMF), a three layers air holes structure of photonic crystal fiber (3PCF), a five layers air holes structure of photonic crystal fiber (5PCF) and a SMF in turn. So the structure SMF-3PCF-5PCF-SMF can be obtained with a total length of 20 mm. During the process of fabrication, the splicing machine parameters and the length of each optical fiber are adjusted to obtain a high sensitivity curvature sensor. The experimental results show that the curvature sensitivity is -8.40 nm/m-1 in the curvature variation range of 0-1.09 m-1, which also show good linearity. In the range of 30-90 °C, the temperature sensitivity is only about 3.24 pm/°C, indicating that the sensor is not sensitive to temperature. The sensor not only has the advantages of easy fabricating, simple structure, high sensitivity but also can solve the problem of temperature measurement cross sensitivity, so it can be used for different areas including aerospace, large-scale bridge, architectural structure health monitoring and so on.

  11. Initiation of Insensitive High Explosives Using Multiple Wave Interactions

    Science.gov (United States)

    Francois, Elizabeth; Burritt, Rosmary; Biss, Matt; Bowden, Patrick

    2017-06-01

    Insensitive High Explosives (IHEs) increase safety in many types of weapons. However, the safety comes at the cost of performance. Initiation of IHE requires large boosters and powerful detonators as well. Multipoint initiation is being utilized to exploit explosive wave interactions to create overdriven states, greatly facilitating the initiation of IHEs. This presentation will build from recent explosive experiments where the minimum spot size for single-point initiation in PBX 9502 was determined. Below this threshold, PBX 9502 could not be initiated. This was then expanded to three initiation points, which were smaller this threshold. Measurements of the velocity and pressure of the wave interactions were measured using Photon Doppler Velocimetry (PDV). Initiation was observed, and the resulting pressures at the double and triple points were found to be above the CJ state for PBX 9502. Based on these results, further tests were conducted to isolate and measure the longevity and pressure of this phenomenon using cut-back tests. All results will be presented and discussed.

  12. Viable supersymmetric model with UV insensitive anomaly mediation

    International Nuclear Information System (INIS)

    Ibe, Masahiro; Kitano, Ryuichiro; Murayama, Hitoshi

    2005-01-01

    We propose an electroweak model which is compatible with the UV insensitive anomaly-mediated supersymmetry breaking. The model is an extension of the next to minimal supersymmetric standard model (NMSSM) by adding vectorlike matter fields which can drive the soft scalar masses of the singlet Higgs field negative and the successful electroweak symmetry breaking is achieved. Viable parameter regions are found to preserve perturbativity of all the coupling constants up to the Planck scale. With this success, the model becomes a perfect candidate of physics beyond the standard model without the flavor changing neutral current and CP problem. The cosmology is also quite interesting. The lightest neutralino is the wino which is a perfect cold dark matter candidate assuming the nonthermal production from the gravitino decay. There is no gravitino problem because it decays before the big-bang nucleosynthesis era, and thus the thermal leptogenesis works. The cosmological domain wall problem inherent in the NMSSM is absent since the Z 3 symmetry is broken by the QCD instanton effect in the presence of the vectorlike quarks. We also briefly comment on a possible solution to the strong CP problem a la the Nelson-Barr mechanism

  13. New selective estrogen and androgen receptor modulators.

    Science.gov (United States)

    Clarke, Bart L; Khosla, Sundeep

    2009-07-01

    The present review focuses on the most significant recent findings regarding selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs). SERMs, which interact with estrogen receptor-alpha and estrogen receptor-beta in multiple tissues, continue to generate clinical interest in potential applications in as many disorders as the tissues in which the two known receptors are found. SARMs have been demonstrated to have fewer clinical applications to date, but continue to be investigated for use in multiple disorders in which androgen receptor modulation is likely to be important. Both types of compounds hold great promise for therapeutic use in multiple hormonal disorders involving tissue-specific effects mediated by estrogen or androgen receptors. Although SERMs have been available for clinical use for 50 years, recent investigation has focused on large randomized clinical trials for newer indications of older agents or smaller clinical trials of newer agents with improved clinical activity and reduced side effects in specific tissues. In particular, the large, prospective, randomized, controlled, multiyear Study of Tamoxifen and Raloxifene and Raloxifene Use in the Heart clinical trials have recently shown interesting similarities and differences between tamoxifen and raloxifene in estrogen-responsive tissues. Lasofoxifene and arzoxifene are two newer SERMs that have recently been demonstrated to improve bone mineral density and lower serum cholesterol values compared with older SERMs in smaller clinical trials. SARMs are a newer category of drug still being investigated mostly at the basic and preclinical level, with fewer clinical trials available for review. SARMs are currently being investigated mostly for use in prostate cancer at different stages but hold promise for multiple other applications. Recent clinical trials indicate that SERMs are useful in treatment of disorders of bone and mineral metabolism and breast cancer

  14. Can we share a pain we never felt? Neural correlates of empathy in patients with congenital insensitivity to pain.

    Science.gov (United States)

    Danziger, Nicolas; Faillenot, Isabelle; Peyron, Roland

    2009-01-29

    Theories of empathy differ regarding the relative contributions of automatic resonance and perspective taking in understanding others' emotions. Patients with the rare syndrome of congenital insensitivity to pain cannot rely on "mirror matching" (i.e., resonance) mechanisms to understand the pain of others. Nevertheless, they showed normal fMRI responses to observed pain in anterior mid-cingulate cortex and anterior insula, two key regions of the so-called "shared circuits" for self and other pain. In these patients (but not in healthy controls), empathy trait predicted ventromedial prefrontal responses to somatosensory representations of others' pain and posterior cingulate responses to emotional representations of others' pain. These findings underline the major role of midline structures in emotional perspective taking and understanding someone else's feeling despite the lack of any previous personal experience of it--an empathic challenge frequently raised during human social interactions.

  15. Masking effect of anti-androgens on androgenic activity in European river sediment unveiled by effect-directed analysis

    NARCIS (Netherlands)

    Weiss, J.M.; Hamers, T.; Thomas, K.; van der Linden, S.C.; Leonards, P.E.G.; Lamoree, M.H.

    2009-01-01

    This study shows that the androgen receptor agonistic potency is clearly concealed by the effects of androgen receptor antagonists in a total sediment extract, demonstrating that toxicity screening of total extracts is not enough to evaluate the full in vitro endocrine disrupting potential of a

  16. RAINBOW TROUT ANDROGEN RECEPTOR ALPHA AND THE HUMAN ANDROGEN RECEPTOR: COMPARISONS IN THE COS WHOLE CELL BINDING ASSAY

    Science.gov (United States)

    Rainbow Trout Androgen Receptor Alpha And Human Androgen Receptor: Comparisons in the COS Whole Cell Binding Assay Mary C. Cardon, L. Earl Gray, Jr. and Vickie S. WilsonU.S. Environmental Protection Agency, ORD, NHEERL, Reproductive Toxicology Division, Research Triangle...

  17. 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

  18. 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

  19. 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.

  20. New insights into androgen treatment of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Louis Gooren

    2006-01-01

    Full Text Available Erectile response in mammals is centrally and peripherally regulated by androgens. Severe hypogonadism in men usually results in loss of libido and potency which can be restored by androgen administration. The original insights into the mechanisms of action of androgens on sexual function indicated that androgens particularly exert effects on libido and that sleep-related erections were androgen-sensitive but erections in response to erotic stimuli were relatively androgen-independent. There are a number of recent developments which shed new light on testosterone treatment of erectile dysfunction in aging men. There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological/biochemical substrate of erectile capacity, reversible upon androgen treatment. Several studies have indicated that the administration of PDE-5-inhibitors is not always sufficient to restore erectile potency in men and that administration of testosterone improves the therapeutical response to PDE-5-inhibitors considerably. There is increasing insight not to view erectile dysfunction (ED as a single entity but as part of the aging process. Circulating levels of testosterone are closely related to manifestations of other etiological factors in ED, such as atherosclerotic disease and diabetes mellitus. The latter are correlated with lower-than-normal testosterone levels.

  1. Androgenic Regulation of Male Sexual Behavior and Physiology in the Syrian Hamster (Mesocricetus Auratus)

    OpenAIRE

    Piekarski, David John

    2012-01-01

    The androgen testosterone (T) and its metabolite, dihydrotestosterone (DHT), are released from the gonads and act in the brain and periphery to control many male-typical traits, including male sexual behavior (MSB). The classical model of androgenic action asserts that T, or DHT binds to a single species of intracellular androgen receptor (AR), that acts as a transcription factor to induce transactivation of androgen-regulated genes. Accordingly, androgens may take hours or days to assert t...

  2. Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology.

    Science.gov (United States)

    Ikeda, Keiko; Baba, Tsuyoshi; Noguchi, Hiroko; Nagasawa, Kunihiko; Endo, Toshiaki; Kiya, Tamotsu; Saito, Tsuyoshi

    2013-02-01

    Does administration of androgen to female-to-male transsexual persons (FTMs) of reproductive age induce polycystic ovary (PCO) morphology? Administration of high-dose androgen to women causes pathognomonic changes to the ovarian cortex and stroma that resemble Stein-Leventhal syndrome but it does not induce PCO morphology. Androgen is thought to play a key role in follicular development and to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). In several experimental models, animals given high-dose androgen show ovarian changes similar to those in women with PCOS. In previous human studies, the ovaries of FTMs who received androgen for long periods also exhibited PCO morphology. We conducted a retrospective case-control study of women, all without PCOS, undergoing salpingo-oophorectomy. The case group consisted of 11 FTMs taking testosterone (duration range: 17 months to 14 years), while the control group consisted of 10 patients with gynaecologic malignancies who did not receive testosterone. Resected ovaries from both groups were compared histologically with respect to changes in the cortex and stroma, and the number of follicles at each maturation stage. Compared with controls, the FTM group had a thicker ovarian cortex (P = 0.0001), and more hyperplastic collagen (P = 0.001), ovarian stromal hyperplasia (P = 0.003) and stromal luteinization, i.e. luteinized stromal cells with a small dark central nucleus surrounded by clear cytoplasm (P = 0.004). Isolated clusters of such stromal luteinized cells were found only in the testosterone-treated ovaries of FTMs. The number of primordial follicles was similar in the two groups (P = 0.22). The numbers of early stage (primary, pre-antral and early antral) follicles, which are dependent on androgen, were also similar (P = 0.81), as were the numbers of antral follicles (P = 0.97). In contrast, significantly greater numbers of atretic follicles were seen in the FTM than that in the control group (P = 0

  3. 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

  4. 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.

  5. 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.

  6. [Bone and Men's Health. Bone selective androgen receptor modulators].

    Science.gov (United States)

    Furuya, Kazuyuki

    2010-02-01

    Androgen, one of the sex steroid hormones shows various biological activities on the corresponding various tissues. Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world. This review focuses on the research and development activities of such SARMs and discuses their usefulness for the treatment of osteoporosis.

  7. Characterization of Sugar Insensitive (sis) Mutants of Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, Susan I.

    2009-06-08

    Despite the fact that soluble sugar levels have been postulated to play an important role in the control of a wide variety of plant metabolic and developmental pathways, the mechanisms by which plants respond to soluble sugar levels remain poorly understood. Plant responses to soluble sugar levels are also important in bioenergy production, as plant sugar responses are believed to help regulate both carbon fixation and carbon partitioning. For example, accumulation of soluble sugars, such as sucrose and glucose, in source tissues leads to feedback inhibition of photosynthesis, thereby decreasing rates of carbon fixation. Soluble sugar levels can also affect sink strengths, affecting the rates of accumulation of carbon-based compounds into both particular molecular forms (e.g. carbohydrates versus lipids versus proteins) and particular plant organs and tissues. Mutants of Arabidopsis that are defective in the ability to respond to soluble sugar levels were isolated and used as tools to identify some of the factors involved in plant sugar response. These sugar insensitive (sis) mutants were isolated by screening mutagenized seeds for those that were able to germinate and develop relatively normal shoot systems on media containing 0.3 M glucose or 0.3 M sucrose. At these sugar concentrations, wild-type Arabidopsis germinate and produce substantial root systems, but show little to no shoot development. Twenty-eight sis mutants were isolated during the course of four independent mutant screens. Based on a preliminary characterization of all of these mutants, sis3 and sis6 were chosen for further study. Both of these mutations appear to lie in previously uncharacterized loci. Unlike many other sugar-response mutants, sis3 mutants exhibit a wild-type or near wild-type response in all phytohormone-response assays conducted to date. The sis6-1 mutation is unusual in that it appears to be due to overexpression of a gene, rather than representing a loss of function mutation

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

    Directory of Open Access Journals (Sweden)

    Kathy Bailey

    Full Text Available 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.

  9. 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.

  10. 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

  11. 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...

  12. 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.

  13. Anabolic androgenic steroid-induced hepatotoxicity.

    Science.gov (United States)

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. [Control measures for anabolic androgenic steroid medicines].

    Science.gov (United States)

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  15. Lipid accumulation product (LAP) is related to androgenicity and cardiovascular risk factors in postmenopausal women.

    Science.gov (United States)

    Maturana, Maria Augusta; Moreira, Roberta M C; Spritzer, Poli Mara

    2011-12-01

    To investigate whether lipid accumulation product (LAP) is related to androgen and sex hormone binding globulin (SHBG) levels and to cardiovascular risk factors in postmenopausal women with no evidence of established cardiovascular disease. Cross-sectional study. LAP (waist-58 × triglycerides [nmol/L]), LAP ≥ arbitrary cutoff point of 34.5, serum testosterone, SHBG, ultrasensitive C-reactive protein (us-CRP). Forty-nine women (mean age 55±5 years; median amenorrhea time 5.5 years [3-8]) were studied: 14% had the metabolic syndrome and 24.5% were hypertensive. Compared with LAP<34.5, LAP ≥ 34.5 (n=29, 59%) was associated with higher testosterone (p=0.021) and free androgen index (FAI) (p=0.003) and lower SHBG levels (p=0.013). Us-CRP (p=0.012), total cholesterol (p=0.041), glucose (p=0.020) and homeostasis model assessment (HOMA) (p=0.019) were higher, and high-density lipoprotein cholesterol (HDL-C) (p=0.001) was lower with LAP ≥ 34.5. LAP was positively correlated with total testosterone (r=0.349, p=0.014), FAI (rs=0.470, p=0.001), us-CRP (r=0.315, p=0.042), systolic (r=0.318, p=0.028) and diastolic (r=0.327, p=0.023) blood pressure, total cholesterol (r=0.498, p<0.001) and glucose (rs=0.319, p=0.026). LAP was negatively correlated with SHBG (rs=-0.430, p=0.003) and HDL-C (r=-0.319, p=0.026). LAP index seems to be associated with androgens and SHBG and with cardiovascular risk factors in postmenopausal women. Also, LAP seems to be a suitable method to screen for cardiovascular risk in postmenopause. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Dietary Carbohydrate Intake Does Not Impact Insulin Resistance or Androgens in Healthy, Eumenorrheic Women.

    Science.gov (United States)

    Sjaarda, Lindsey A; Schisterman, Enrique F; Schliep, Karen C; Plowden, Torie; Zarek, Shvetha M; Yeung, Edwina; Wactawski-Wende, Jean; Mumford, Sunni L

    2015-08-01

    Diet is proposed to contribute to androgen-related reproductive dysfunction. This study evaluated the association between dietary macronutrient intake, carbohydrate fraction intake, and overall diet quality on androgens and related hormones, including anti-Müllerian hormone (AMH) and insulin, in healthy, regularly menstruating women. This was a prospective cohort study from 2005 and 2007. The study was conducted at the University at Buffalo, western New York State, USA. Participants were 259 eumenorrheic women without a self-reported history of infertility, polycystic ovary syndrome (PCOS), or other endocrine disorder. A 24-hour dietary recall was administered 4 times per menstrual cycle, and hormones were measured 5 to 8 times per cycle for 1 (n = 9) or 2 (n = 250) cycles per woman (n = 509 cycles). Associations between the dietary intake of carbohydrates (starch, sugar, sucrose, and fiber), macronutrients, overall diet quality and hormones (insulin, AMH, and total and free testosterone), as well as the relationship of dietary intake with occurrences of high total testosterone combined with high AMH (fourth quartile of each), ie, the "PCOS-like phenotype," were assessed. No significant relationships were identified between dietary intake of carbohydrates, percent calories from any macronutrient or overall diet quality (ie, Mediterranean diet score) and relevant hormones (insulin, AMH, and total and free testosterone). Likewise, no significant relationships were identified between dietary factors and the occurrence of a subclinical PCOS-like phenotype. Despite evidence of a subclinical continuum of a PCOS-related phenotype of elevated androgens and AMH related to sporadic anovulation identified in previous studies, dietary carbohydrate and diet quality do not appear to relate to these subclinical endocrine characteristics in women without overt PCOS.

  17. PAC-3 Insensitive Munitions/Final Hazard Classification (IM/FHC) Test Program and Multimedia Database

    National Research Council Canada - National Science Library

    Vittitow, Patricia

    1996-01-01

    ...) and full-scale testing has been completed at Eglin Air Force Base, Florida. The unique configurations of some of the full-scale tests proved challenging in satisfying both insensitive munitions (IM...

  18. 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.

  19. Surfactant for dye-penetrant inspection is insensitive to liquid oxygen

    Science.gov (United States)

    1966-01-01

    LOX insensitive solvent is blended into a mixture of commercially available surfactants to clean metal surfaces which are to be investigated by the dye-penetrant method. The surfactant mixture is applied before and after application of the dye.

  20. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, W

    2003-01-01

    ... prostate. Castration of mice stimulates B and T lymphopoiesis, thymic and bone marrow hyperplasia. The induction of apoptotic cell death following androgen ablation is accompanied by an inflammatory infiltrate comprised predominantly of activated T cells...

  1. 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.

  2. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2016-10-01

    report. Inventions, patent applications, and/or licenses Nothing to report. Others Nothing to report. 7. Participants & Other... Brand LJ et al: Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res

  3. Regulation of Androgen Responses in Prostate Cancer by BAG-1

    National Research Council Canada - National Science Library

    Reed, John

    2001-01-01

    .... However, nearly all tumors eventually relapse as hormone-refractory disease. A need therefore exists for better understanding of the mechanisms that allow prostate cancer cells to grow in an androgen - independent manner...

  4. Regulation of Androgen Responses in Prostate Cancer by BAG-1

    National Research Council Canada - National Science Library

    Reed, John

    1999-01-01

    .... However, nearly all tumors eventually relapse as hormone- refractory disease. A need therefore exists for better understanding of the mechanisms that allow prostate cancer cells to grow in an androgen - independent manner...

  5. Male osteoporosis and androgenic therapy: from testosterone to SARMs.

    Science.gov (United States)

    Cilotti, Antonio; Falchetti, Alberto

    2009-09-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance.Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials.

  6. Vocal cues to male androgen levels in giant pandas.

    Science.gov (United States)

    Charlton, Benjamin D; Keating, Jennifer L; Kersey, David; Rengui, Li; Huang, Yan; Swaisgood, Ronald R

    2011-02-23

    Little is known about the potential of non-human mammal vocalizations to signal information on the hormonal status of the caller. In the current study, we used endocrine data and acoustic analyses to determine whether male giant panda bleats provide reliable information about the caller's current androgen levels. Our results revealed significant relationships between acoustic features of male giant panda bleats and the caller's faecal androgen metabolite concentrations. To our knowledge, this constitutes the first demonstration that the acoustic structure of a non-human mammal call has the potential to yield information about the caller's current androgen levels. We go on to discuss the anatomical basis for our findings and the potential functional relevance of signalling information on male androgen levels in giant panda sexual communication.

  7. 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...

  8. 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....

  9. Single-nucleotide polymorphism in the 5-alpha-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors

    NARCIS (Netherlands)

    Boer, Hink; Westerink, Nico-Derk L.; Altena, Renske; Nuver, Janine; Dijck-Brouwer, D. A. Janneke; van Faassen, Martijn; Klont, Frank; Kema, Ido P.; Lefrandt, Joop D.; Zwart, Nynke; Boezen, H. Marike; Smit, Andries J.; Meijer, Coby; Gietema, Jourik A.

    Purpose: Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-alpha-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated

  10. Impact of Early Postnatal Androgen Exposure on Voice Development

    Science.gov (United States)

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  11. 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....

  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. Aberrant AR Signaling as a Function of Declining Androgen

    Science.gov (United States)

    2005-03-01

    Ser 133) obtained from the American Type Culture Collection located within a transcriptionally critical region called G\\’lanassas, VA, USA) and grown...p300 and its activation via the PIKA pathway. cells toward androgen independence with respect to Western blot data indicated that CREB phosphorylation...presence of obtained from the American Type Culture Collection (Manassas, V.A) and dihydrotestosterone after androgen receptor knock-down. We C4-2B

  14. Nonsteroidal Selective Androgen Receptor Modulators Enhance Female Sexual Motivation

    OpenAIRE

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B.; He, Yali; Siddam, Anjaiah; Miller, Duane D.; Dalton, James T.

    2010-01-01

    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 eval...

  15. Selective androgen receptor modulators in preclinical and clinical development

    OpenAIRE

    Narayanan, Ramesh; Mohler, Michael L.; Bohl, Casey E.; Miller, Duane D.; Dalton, James T.

    2008-01-01

    Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on prostate and other secondary sexual organs. SARMs provide therapeutic o...

  16. 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

  17. 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

    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 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. PMID:27807202

  18. Anabolic-androgenic steroid increases running endurance in rats.

    Science.gov (United States)

    Van Zyl, C G; Noakes, T D; Lambert, M I

    1995-10-01

    The study was designed to determine whether treatment with an anabolic-androgenic steroid enhances running performance in rats by increasing their freely chosen training distance. Forty male Long-Evans rats were randomly divided into either a sedentary control group or an exercising group caged in specially designed running wheels in which the rats were able to run spontaneously. After 4 wk, both groups were further subdivided into two groups receiving either 0.5-mg Durabolin (nandrolone phenylpropionate) (im) or 0.5-mg saline, every second day. After 8 wk, running distance was similar in both exercising groups. Rats receiving the anabolic-androgenic steroid ran 41% longer during the test of submaximal running endurance compared to the trained rats receiving saline (P sedentary rats receiving the anabolic-androgenic steroid. After 4 wk of training, the maximal sprinting speed increased by 29% in trained rats. There was no further increase in maximal sprinting speed after an additional 4 wk of training and treatment with either anabolic-androgenic steroid or saline treatment. Therefore, rats that train spontaneously while being treated with an anabolic-androgenic steroid had increased submaximal running endurance compared with trained rats treated with saline, despite the similar voluntary training distance and skeletal muscle oxidative capacity between the two groups. The mechanism by which treatment with an anabolic-androgenic steroid, combined with training, enhances submaximal running performance could not be identified and needs to be addressed in future studies.

  19. Enhanced evaluation of selective androgen receptor modulators in vivo.

    Science.gov (United States)

    Otto-Duessel, M; He, M; Adamson, T W; Jones, J O

    2013-01-01

    Selective androgen receptor modulators (SARMs) are a class of drugs that control the activity of the androgen receptor (AR), which mediates the response to androgens, in a tissue-selective fashion. They are specifically designed to reduce the possible complications that result from the systemic inhibition or activation of AR in patients with diseases that involve androgen signalling. However, there are no ideal in vivo models for evaluating candidate SARMs. Therefore, we created a panel of androgen-responsive genes in clinically relevant AR expressing tissues including prostate, skin, bone, fat, muscle, brain and kidney. We used select genes from this panel to compare transcriptional changes in response to the full agonist dihydrotestosterone (DHT) and the SARM bolandiol at 16 h and 6 weeks. We identified several genes in each tissue whose expression at each of these time points correlates with the known tissue-specific effects of these compounds. For example, in the prostate we found four genes whose expression was much lower in animals treated with bolandiol compared with animals treated with DHT for 6 weeks, which correlated well with differences in prostate weight. We demonstrate that adding molecular measurements (androgen-regulated gene expression) to the traditional physiological measurements (tissue weights, etc.) makes the evaluation of potential SARMs more accurate, thorough and perhaps more rapid by allowing measurement of selectivity after only 16 h of drug treatment. © 2012 American Society of Andrology and European Academy of Andrology.

  20. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    Science.gov (United States)

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  1. [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.

  2. 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.

  3. Do anabolic-androgenic steroids have performance-enhancing effects in female athletes?

    Science.gov (United States)

    Huang, Grace; Basaria, Shehzad

    2018-03-15

    Doping with anabolic-androgenic steroids (AAS) is common among both male and female athletes and is a growing public health problem. Review of historical data of systematic state-sponsored doping programs implemented by the German Democratic Republic in elite female athletes and from clinical trials of testosterone administration in non-athlete women suggests that AAS have ergogenic effects in women. The use of AAS in female athletes has been associated with adverse effects that include acne, hirsutism, deepening of the voice and menstrual disturbances; life-threatening adverse effects such as cardiac arrhythmias and sudden death have also been reported. Therefore, detection of AAS abuse in female athletes is important to ensure fairness in competition; at the same time, the athletes should be educated regarding the adverse consequences of AAS use. Although administration of exogenous androgens have been associated with ergogenic effects, it remains unclear whether endogenous hyperandrogenism seen in some medical conditions such as disorders of sexual development (DSD), congenital adrenal hyperplasia and polycystic ovary syndrome, confers any competitive advantage. Well-designed studies are needed to determine the effects of endogenous hyperandrogenism on athletic performance in female athletes. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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.

  5. Long-term Effects Of Perinatal Androgenization On Reproductive Parameters Of Male Rat Offspring Androgenization And Male Rat Reproduction.

    OpenAIRE

    Guerra, M T; Perobelli, J E; Sanabria, M; Anselmo-Franci, J A; Kempinas, W De Grava

    2015-01-01

    It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype. Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction. Pregnant Wistar rats were administered either corn oil (vehicle) or testosterone propionate at 0.2 mg/kg from gestational day 12 until the end of lactation and the reproductive function of male off spring was evalu...

  6. P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells.

    Science.gov (United States)

    Fedoruk, Matthew N; Giménez-Bonafé, Pepita; Guns, Emma S; Mayer, Lawrence D; Nelson, Colleen C

    2004-04-01

    P-glycoprotein (P-gp) is commonly associated with multi-drug resistance (MDR) in cancer cells and the efflux of a broad spectrum of chemicals from the cell, including many chemotherapeutics and certain steroid hormones. The impact of P-gp and mechanisms involved in androgen transport and cellular accumulation within normal and malignant prostate cells remains unclear. Following incubation of LNCaP, PC-3, HeLa, and HeLa FLAG-androgen receptor (AR) cells with (3)H-dihydrotestosterone (DHT) alone and in combination with P-gp inhibitors, PSC-833 and verapamil, we examined the cellular accumulation and efflux of androgens, as well as gene transcriptional response. Our data reveal that the cellular transport and accumulation of DHT is dependent on the expression of functional AR and modulated by P-gp. P-gp over-expression by both transient transfection and aspirin treatment in LNCaP cells showed decreased intracellular DHT accumulation, further suggesting DHT efflux is P-gp regulated. Androgen responsiveness may be modulated by P-gp in prostate cancer cells. The biological consequences of increased P-gp expression are decreased androgen accumulation and a corresponding decrease in androgen-regulated transcriptional activity and PSA gene expression. Copyright 2004 Wiley-Liss, Inc.

  7. 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.

  8. Androgens and adipose tissue in males: a complex and reciprocal interplay.

    Science.gov (United States)

    Mammi, Caterina; Calanchini, Matilde; Antelmi, Antonella; Cinti, Francesca; Rosano, Giuseppe M C; Lenzi, Andrea; Caprio, Massimiliano; Fabbri, Andrea

    2012-01-01

    Clinical evidence shows that in males obesity is frequently associated with hypogonadism and vice versa; also, low testosterone levels have been considered a "hallmark" of metabolic syndrome in men. These observations indicate that there is a strict connection between anatomically and functionally distinct cell types such as white adipocytes and Leydig cells, that synthesize testosterone. Adipose tissue is able to control several functions of the testis through its products secreted in the bloodstream. On the other hand, circulating levels of testosterone and estradiol deeply affect adipocyte proliferation, differentiation, and fat mass distribution, hereby controlling critical metabolic functions, such as food intake, insulin sensitivity, vascular reactivity, and immunity. This paper highlights the existing clinical and experimental evidence linking androgens and adipose tissue and illustrates the consequences occurring when the balance between fat mass distribution and eugonadism is lost.

  9. Androgens and Adipose Tissue in Males: A Complex and Reciprocal Interplay

    Directory of Open Access Journals (Sweden)

    Caterina Mammi

    2012-01-01

    Full Text Available Clinical evidence shows that in males obesity is frequently associated with hypogonadism and vice versa; also, low testosterone levels have been considered a “hallmark” of metabolic syndrome in men. These observations indicate that there is a strict connection between anatomically and functionally distinct cell types such as white adipocytes and Leydig cells, that synthesize testosterone. Adipose tissue is able to control several functions of the testis through its products secreted in the bloodstream. On the other hand, circulating levels of testosterone and estradiol deeply affect adipocyte proliferation, differentiation, and fat mass distribution, hereby controlling critical metabolic functions, such as food intake, insulin sensitivity, vascular reactivity, and immunity. This paper highlights the existing clinical and experimental evidence linking androgens and adipose tissue and illustrates the consequences occurring when the balance between fat mass distribution and eugonadism is lost.

  10. 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.

  11. 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).

  12. 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.

  13. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects

    DEFF Research Database (Denmark)

    Sharpe, R.M.; Skakkebæk, Niels Erik

    2008-01-01

    Reproductive disorders of newborn (cryptorchidism, hypospadias) and young adult males (low sperm counts, testicular germ cell cancer) are common and/or increasing in incidence. It has been hypothesized that these disorders may comprise a testicular dysgenesis syndrome (TDS) with a common origin...... androgen production/action during fetal testis development, may play in the origin of downstream disorders Udgivelsesdato: 2008/2...

  14. 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 ...

  15. 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 ...

  16. 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...

  17. 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...

  18. Androgenic-anabolic activities of some new synthesized steroidal pyrane, pyridine and thiopyrimidine derivatives.

    Science.gov (United States)

    Abdalla, Mohamed M; Amr, Abd El-Galil E; Al-Omar, Mohamed A; Hussain, Azza A; Amer, Mohamed S

    2014-01-01

    In continuation of our previous work, fused steroidal derivatives with pyrane, pyridine, pyrimidine moieties were synthesized and evaluated as androgenic-anabolic agents. Some of the newly synthesized compounds are exhibited pronounced androgenic-anabolic activities.

  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. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Kaaks, R.; Rinaldi, S.; Key, T.J.; Berrino, F.; Peeters, P.H.M.; Biessy, C.; Dossus, L.; Lukanova, A.; Bingham, S.; Khaw, K-T.; Allen, N.E.; Bueno-de-Mesquita, H.B.; Gils, C.H. van; Grobbee, D.E.; Boeing, H.; Lahmann, P.H.; Nagel, G.; Chang-Claude, J.; Clavel-Chapelon, F.; Fournier, A.; Thiébaut, A.; Gonzalez, C.A.; Quirós, J.R.; Tormo, M-J.; Ardanaz, E.; Amiano, P.; Krogh, V.; Palli, D.; Panico, S.; Tumino, R.; Vineis, P.; Trichopoulou, A.; Kalapothaki, V.; Trichopoulos, D.; Ferrari, P.; Norat, T.; Saracci, R.; Riboli, E.

    2005-01-01

    Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has

  1. Endogenous androgens and carotid intimal-medial thickness in women.

    Science.gov (United States)

    Bernini, G P; Sgro', M; Moretti, A; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    1999-06-01

    The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.

  2. 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.

  3. Three Genes That Affect Sugar Sensing (Abscisic Acid Insensitive 4, Abscisic Acid Insensitive 5, and Constitutive Triple Response 1) Are Differentially Regulated by Glucose in Arabidopsis1

    Science.gov (United States)

    Arroyo, Analilia; Bossi, Flavia; Finkelstein, Ruth R.; León, Patricia

    2003-01-01

    Mutant characterization has demonstrated that ABI4 (Abscisic Acid [ABA] Insensitive 4), ABI5 (ABA Insensitive 5), and CTR1 (Constitutive Triple Response 1) genes play an important role in the sugar signaling response in plants. The present study shows that the transcripts of these three genes are modulated by glucose (Glc) independently of the developmental arrest caused by high Glc concentrations. ABI4 and ABI5 transcripts accumulate in response to sugars, whereas the CTR1 transcript is transiently reduced followed by a rapid recovery. The results of our kinetic studies on gene expression indicate that ABI4, ABI5, and CTR1 are regulated by multiple signals including Glc, osmotic stress, and ABA. However, the differential expression profiles caused by these treatments suggest that distinct signaling pathways are used for each signal. ABI4 and ABI5 response to the Glc analog 2-deoxy-Glc supports this conclusion. Glc regulation of ABI4 and CTR1 transcripts is dependent on the developmental stage. Finally, the Glc-mediated regulation of ABI4 and ABI5 is affected in mutants displaying Glc-insensitive phenotypes such as gins, abas, abi4, abi5, and ctr1 but not in abi1-1, abi2-1, and abi3-1, which do not show a Glc-insensitive phenotype. The capacity of transcription factors, like the ones analyzed in this work, to be regulated by a variety of signals might contribute to the ability of plants to respond in a flexible and integral way to continuous changes in the internal and external environment. PMID:12970489

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

    OpenAIRE

    Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard 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...

  5. Andrographolide Targets Androgen Receptor Pathway in Castration-Resistant Prostate Cancer

    OpenAIRE

    Liu, Chengfei; Nadiminty, Nagalakshmi; Tummala, Ramakumar; Chun, Jae Yeon; Lou, Wei; Zhu, Yezi; Sun, Meng; Evans, Christopher P.; Zhou, Qinghua; Gao, Allen C.

    2011-01-01

    Androgen receptor (AR) signaling not only plays a pivotal role in the development of androgen-dependent prostate cancer but is also important in the growth and survival of castration-resistant prostate cancer (CRPC). The first line of treatment of androgen-dependent prostate cancer is the use of androgen deprivation therapy. However, most patients will eventually relapse due to development of CRPC. Thus, development of a strategy to target AR for treatment of CRPC is urgently needed. The auth...

  6. Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy-Resistant Prostate Cancer

    Science.gov (United States)

    2017-10-01

    hormones that play a critical role in stimulating prostate cancer growth . Androgens activate a protein called the androgen receptor (AR), which...variants, and evaluating if they block androgen-dependent prostate cancer cell growth . To understand how these molecule blocks AR function , we will...regulates genes involved in cell growth . Although powerful anti-androgen drugs can be administered to block AR action and have been used successfully to

  7. Th17-Associated Cytokines as a Therapeutic Target for Steroid-Insensitive Asthma

    Directory of Open Access Journals (Sweden)

    Yuko Morishima

    2013-01-01

    Full Text Available Steroid-insensitive asthma is an infrequent but problematic airway disease that presents with persistent symptoms, airflow limitation, or recurrent exacerbations even when treated with steroid-based therapies. Because of unsatisfactory results obtained from currently available therapies for steroid-insensitive asthma, a better understanding of its pathogenesis and the development of new targeted molecular therapies are warranted. Recent studies indicated that levels of interleukin (IL-17 are increased and both eosinophils and neutrophils infiltrate the airways of severe asthmatics. IL-17 is a proinflammatory cytokine mainly secreted from helper T (Th 17 cells and is important for the induction of neutrophil recruitment and migration at sites of inflammation. This review focuses on the pathogenetic role of Th17 cells and their associated cytokines in steroid-insensitive asthma and discusses the prospects of novel therapeutic options targeting the Th17 signaling pathway.

  8. 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.

  9. Maternal yolk androgens stimulate territorial behaviour in black-headed gull chicks

    NARCIS (Netherlands)

    Mueller, Wendt; Dijkstra, Cor; Groothuis, Ton G. G.

    2009-01-01

    Avian eggs contain substantial amounts of maternal androgens. The concentrations of these yolk androgens are affected by the maternal environment, such as the level of social competition, parasite exposure or food conditions. Since yolk androgens have been shown to affect a wide array of offspring

  10. 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.

  11. 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......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...

  12. Matrix-insensitive protein assays push the limits of biosensors in medicine

    DEFF Research Database (Denmark)

    Gaster, Richard S; Hall, Drew A; Nielsen, Carsten Haagen

    2009-01-01

    Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse....... Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our...

  13. Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.

    Science.gov (United States)

    Pagán, Oné R; Montgomery, Erica; Deats, Sean; Bach, Daniel; Baker, Debra

    2015-10-01

    Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism.

  14. 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.

  15. 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.

  16. The Central Effects of Androgenic-anabolic Steroid Use.

    Science.gov (United States)

    Mędraś, Marek; Brona, Anna; Jóźków, Paweł

    2018-02-21

    : 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.

  17. QSAR models for anti-androgenic effect - a preliminary study

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Nikolov, Nikolai Georgiev; Wedebye, Eva Bay

    2011-01-01

    Three modelling systems (MultiCase (R), LeadScope (R) and MDL (R) QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78......-91% and sensitivity of 51-76%. The specificity was highest in the MultiCase (R) model and the sensitivity was highest in the MDL (R) QSAR model. A complementary use of the models may be a valuable tool when optimizing the prediction of chemicals for androgenic receptor antagonism. When evaluating the fitness...

  18. Influence of obesity and androgen deficiency on prostatic blood circulation

    Directory of Open Access Journals (Sweden)

    I. A. Tyuzikov

    2012-01-01

    Full Text Available In Study at 120 Diabetes Mellitus II type men the high frequency Obesity (71,7% and Androgen Deficiency (52,8—64,5% of the patients depending on a degree of the indemnification and them pathogenic authentic communications were shown. The blood level of total testosterone was represented by the critical factor of Prostatic arterial Blood Circulation. Obesity and Androgen Deficiency are seem as independent risk factors to development of ischemic prostatopathy, such as Prostatic blood circulation Disorders can develop earlier than other variants of the diabetic microangiophaty.

  19. Optimizing Ligand Efficiency of Selective Androgen Receptor Modulators (SARMs).

    Science.gov (United States)

    Handlon, Anthony L; Schaller, Lee T; Leesnitzer, Lisa M; Merrihew, Raymond V; Poole, Chuck; Ulrich, John C; Wilson, Joseph W; Cadilla, Rodolfo; Turnbull, Philip

    2016-01-14

    A series of selective androgen receptor modulators (SARMs) containing the 1-(trifluoromethyl)benzyl alcohol core have been optimized for androgen receptor (AR) potency and drug-like properties. We have taken advantage of the lipophilic ligand efficiency (LLE) parameter as a guide to interpret the effect of structural changes on AR activity. Over the course of optimization efforts the LLE increased over 3 log units leading to a SARM 43 with nanomolar potency, good aqueous kinetic solubility (>700 μM), and high oral bioavailability in rats (83%).

  20. 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 ...

  1. An Investigation into an Alternative Fragment Projector for Insensitive Munitions Qualification

    National Research Council Canada - National Science Library

    Lam, C

    1997-01-01

    ... to the 12.7 mm steel cubes used in the Fragmat Insensitive Munition test. A large number of EFP designs were modelled using the PC-DYNA2D computer hydrocode and short listed candidates were fabricated for experimental verification...

  2. 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

  3. Delay-Insensitive Synchronization on a Message-Passing Architecture with an Open Collector Bus

    NARCIS (Netherlands)

    Bekker, H.; Dijkstra, E.J.

    1996-01-01

    The performance of some algorithms, running on a message passing computer; is limited by the high latency of global communications. To increase the performance, a simple open collector bus, operated by delay insensitive programs running on each processor can be used. We illustrate this by an

  4. The management of patients with polycystic ovary syndrome.

    Science.gov (United States)

    Jayasena, Channa N; Franks, Stephen

    2014-10-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. The syndrome is typified by its heterogeneous presentation, which includes hirsutism (a function of hypersecretion of ovarian androgens), menstrual irregularity and infertility (that is due to infrequent or absent ovulation). Furthermore, PCOS predisposes patients to metabolic dysfunction and an increased risk of type 2 diabetes mellitus (T2DM). The aetiology of the syndrome has a major genetic component. Obesity exacerbates the insulin resistance that is a feature of PCOS in many women and amplifies the clinical and biochemical abnormalities. In clinical practice, the choice of investigations to be done depends mainly on the presenting symptoms. The approach to management is likewise dependent on the presenting complaint. Symptoms of androgen excess (hirsutism, acne and alopecia) require cosmetic measures, suppression of ovarian androgen function and anti-androgen therapy, alone or in combination. Ovulation rate is improved by diet and lifestyle intervention in overweight individuals but induction of ovulation by, in the first instance, anti-estrogens is usually required. Monitoring of glucose is important in overweight women and/or those with a family history of T2DM. Metformin is indicated for women with impaired glucose tolerance but whether this drug is otherwise useful in women with PCOS remains debatable.

  5. 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.

  6. 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

  7. 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.

  8. Anti-androgenic activity of Xylopic acid in orchidectomerized rats ...

    African Journals Online (AJOL)

    To characterize anti-androgenic properties of xylopic acid (XA) and to elucidate the possible mech-anism of the antifertility activity of XA, XA was administered to orchidectomized rats following the Hershberger assay protocol. Thirty male Sprague-Dawley rats were orchidectomized or sham oper-ated at 42 days of age.

  9. Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer

    NARCIS (Netherlands)

    Langenhuijsen, J.F.; Badhauser, D.; Schaaf, B.; Kiemeney, L.A.L.M.; Witjes, J.A.; Mulders, P.F.A.

    2013-01-01

    OBJECTIVES: To analyze the predictive value of PSA for progression and the role of testosterone for quality of life (QOL) in patients with androgen deprivation therapy (ADT) for metastatic prostate cancer. MATERIALS AND METHODS: PSA and testosterone data were used from a phase III trial randomizing

  10. 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 ...

  11. 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...

  12. 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…

  13. 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)

  14. 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.

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

    African Journals Online (AJOL)

    1990-01-31

    Jan 31, 1990 ... 1991,26(1). Plasma androgen concentrations in initial samples from spotted hyaenas immobilized with Zoletil (CI-744) reflect hormonal status estimated by GnRH challenge and immobilization stress response. A.S. van Jaarsveld * and J.D. Skinner. Mammal Research Institute, University of Pretoria, Pretoria ...

  16. Changes in gene expression following androgen receptor blockade ...

    Indian Academy of Sciences (India)

    Madhu urs

    Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well- documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate, it is not clear whether all the gene expression changes ...

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

    Indian Academy of Sciences (India)

    BALACHANDRAN SARANYA

    male breast cancer (Wooster et al. 1992) and prostate cancer. (Tilley et al. 1996). The two most important androgens are testosterone and. 5α-dihydrotestosterone, whose actions ..... Among the steroid recep- tors, the AR records the highest density, witnessing more than 600 different mutations leading to AIS (Gottlieb et al.

  18. 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.

  19. Androgenic potential and anther in vitro culture of Lagenaria ...

    African Journals Online (AJOL)

    Androgenic potential and anther in vitro culture of Lagenaria siceraria (Molina) Standl an edible-seed cucurbit. Kouakou Laurent Kouakou, Tra Serge Doubi, Tra Serge Koffi, Kouadio Ignace Kouassi, Tanoh Hilaire Kouakou, Jean-Pierre Baudoin, Irié Arsène Zoro Bi ...

  20. Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer.

    Science.gov (United States)

    Hwang, Dong Jin; Yang, Jun; Xu, Huiping; Rakov, Igor M; Mohler, Michael L; Dalton, James T; Miller, Duane D

    2006-10-01

    A new series of androgen receptor targeted agents (ARTA) was prepared and tested in androgen-dependent and -independent prostate cancer cell lines. These agents were bicalutamide analogs with isothiocyanato substituted B-rings. Also, the linker sulfone of R-bicalutamide was maintained or replaced with several alternative linkages including ether, amine, N-methylamine, thioether, and methylene (in this case the product was a racemic mixture) functional groups at the X-position. To expand the structure-activity relationship (SAR) of these arylisothiocyanato AR ligands, B-ring halogenated arylisothiocyanato ligands were also prepared and tested. The arylisothiocyanato AR ligands showed strong binding affinities to AR ranging from 0.6 to 54 nM. Among them, thioether and ether linkages demonstrated high binding affinities (0.6 and 4.6 nM, respectively) and selective cell growth inhibition (approximately 3- to 6-fold) for LNCaP, an androgen-dependent prostate cancer cell line, when compared to the androgen independent prostate cell lines (DU145, PC-3, and PPC-1) and a bladder cell line (TSU-Pr1). However, the ligands were inactive (IC50>100 mM) in a normal monkey kidney cell line (CV-1) that was used as the control for non-specific toxicity.

  1. 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

  2. Efficacy Against Human Prostate Cancer by Prostate-specific Membrane Antigen-specific, Transforming Growth Factor-β Insensitive Genetically Targeted CD8+T-cells Derived from Patients with Metastatic Castrate-resistant Disease.

    Science.gov (United States)

    Zhang, Qiang; Helfand, Brian T; Carneiro, Benedito A; Qin, Weijun; Yang, Ximing J; Lee, Chung; Zhang, Weipeng; Giles, Francis J; Cristofanilli, Massimo; Kuzel, Timothy M

    2017-12-21

    Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8 + T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8 + T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station. We developed a chimeric antigen receptor retroviral construct using an anti-PSMA chimeric immunoglobulin-T-cell receptor(ζ) gene (PZ1) and dominant negative TGF-ß type II receptor (TßRIIDN), that could induce CD8 + T-cells to be PSMA reactive and insensitive to TGF-ß. Cr 51 release assay was performed on PC-3 and PC-3-PSMA. The further antitumor functions of PSMA-specific, TGF-ß insensitive CD8 + T-cells was evaluated using an immunodeficient RAG-1 -/- mouse model. We found PSMA-specific, TGF-ß insensitive CD8 + T-cells from mCRPC were expanded with strong expression of PZ1 and thymidine kinase genes, and their growth was not suppressed by TGF-ß. The survival of these cells decreased sharply after treatment with ganciclovir. Treatment of PSMA-specific TGF-ß, insensitive CD8 + T-cells was associated with 61.58% specific lysis on PC-3-PSMA, and significantly suppressed PC3-PSMA tumor compared with the PC3 tumor. A large amount of tumor apoptosis and CD8 + T-cell infiltration were found only in the PC3-PSMA tumor. This study verified that PSMA-specific, TGF-ß insensitive CD8 + T-cells derived from mCRPC patients could be successfully expanded and used to overcome the immunosuppressive effects of the tumor microenvironment to control PSMA-expressing PC in vitro and in vivo. This may provide a promising approach for men with mCRPC who fail androgen deprivation therapy. We investigated the role of a novel chimeric antigen

  3. 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.

  4. 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.

  5. Similarities and Distinctions in Actions of Surface-Directed and Classic Androgen Receptor Antagonists.

    Directory of Open Access Journals (Sweden)

    Ji Ho Suh

    Full Text Available The androgen receptor (AR surface-directed antagonist MJC13 inhibits AR function and proliferation of prostate cancer (PC cells. These effects are related to arrest of an AR/chaperone complex in the cytoplasm. Here, we compared MJC13 and classic AR antagonists such as flutamide and bicalutamide. Microarray analysis and confirmatory qRT-PCR reveals that MJC13 and flutamide inhibit dihydrotestosterone (DHT-dependent genes in LNCaP PC cells. Both compounds are equally effective on a genome wide basis and as effective as second generation AR antagonists (MDV3100, ARN-509 at selected genes. MJC13 inhibits AR binding to the prostate specific antigen (PSA promoter more strongly than flutamide, consistent with different mechanisms of action. Examination of efficacy of MJC13 in conditions that reflect aspects castrate resistant prostate cancer (CRPC reveals that it inhibits flutamide activation of an AR mutant (ART877A that emerges during flutamide withdrawal syndrome, but displays greatly restricted gene-specific activity in 22Rv1 cells that express a constitutively active truncated AR and is inactive against glucocorticoid receptor (GR, which can co-opt androgen-dependent signaling networks in CRPC. Importantly, MJC13 inhibits AR interactions with SRC2 and β-catenin in the nucleus and, unlike flutamide, strongly inhibits amplification of AR activity obtained with transfected SRC2 and β-catenin. MJC13 also inhibits DHT and β-catenin-enhanced cell division in LNCaP cells. Thus, a surface-directed antagonist can block AR activity in some conditions in which a classic antagonist fails and may display utility in particular forms of CRPC.

  6. 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.

  7. A single conserved basic residue in the potassium channel filter region controls KCNQ1 insensitivity toward scorpion toxins.

    Science.gov (United States)

    Chen, Zongyun; Hu, Youtian; Wang, Bin; Cao, Zhijian; Li, Wenxin; Wu, Yingliang

    2015-09-01

    Although many studies concerning the sensitivity mechanism of scorpion toxin-potassium channel interactions have been reported, few have explored the biochemical insensitivity mechanisms of potassium channel receptors toward natural scorpion toxin peptides, such as the KCNQ1 channel. Here, by sequence alignment analyses of the human KCNQ1 channel and scorpion potassium channel MmKv2, which is completely insensitive to scorpion toxins, we proposed that the insensitivity mechanism of KCNQ1 toward natural scorpion toxins might involve two functional regions, the turret and filter regions. Based on this observation, a series of KCNQ1 mutants were constructed to study molecular mechanisms of the KCNQ1 channel insensitivity toward natural scorpion toxins. Electrophysiological studies of chimera channels showed that the channel filter region controls KCNQ1 insensitivity toward the classical scorpion toxin ChTX. Interestingly, further residue mutant experiments showed that a single basic residue in the filter region determined the insensitivity of KCNQ1 channels toward scorpion toxins. Our present work showed that amino acid residue diversification at common sites controls the sensitivity and insensitivity of potassium channels toward scorpion toxins. The unique insensitivity mechanism of KCNQ1 toward natural scorpion toxins will accelerate the rational design of potent peptide inhibitors toward this channel.

  8. 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

  9. Influence of endogenous androgens on carotid wall in postmenopausal women.

    Science.gov (United States)

    Bernini, G P; Moretti, A; Sgró, M; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    2001-01-01

    There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may

  10. Serum androgen profile and physical performance in women Olympic athletes.

    Science.gov (United States)

    Eklund, Emma; Berglund, Bo; Labrie, Fernand; Carlström, Kjell; Ekström, Lena; Hirschberg, Angelica Lindén

    2017-09-01

    The role of endogenous androgens for body composition and physical performance in women athletes is still not elucidated. To examine the serum androgen profile in relation to body composition and physical performance in women Olympic athletes and to compare endocrine variables and body composition to controls. Cross-sectional study, conducted between 2011 and 2015 at the Women's Health Research Unit, Karolinska University Hospital, Stockholm. Swedish women Olympic athletes (n=106) and age-matched and body mass index-matched sedentary controls (n=117) were included in the study. Blood sampling was performed in a rested, fasting state for the measurement of serum androgens and their metabolites by liquid chromatography-tandem mass spectrometry. Body composition was determined by dual-energy X-ray absorptiometry (controls n=100, athletes n=65). The athletes performed standardised performance tests (n=59) (squat jump (SJ) and countermovement jump (CMJ). The athletes demonstrated significantly higher levels of the precursor androgens dehydroepiandrosterone (DHEA) and 5-androstene-3β, 17β-diol (5-DIOL) and the metabolite etiocholanolone glucuronide (Etio-G), significantly lower levels of estrone (pathletes. DHEA and lean mass legs explained 66% of the variance in SJ, whereas lean mass explained 52% of the variance in CMJ. The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. 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.

  12. Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA- Mediated Androgen Receptor Gene Silencing

    Science.gov (United States)

    2008-02-01

    mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem 2002;277:49374–82. 39. Wright ME, Tsai MJ, Aebersold R. Androgen receptor...two orders of magnitude better than nanowire arrays, but these assays require extensive labeling and mul- tiple chemical and biochemical manipulations

  13. Development of an endogenous androgen receptor-mediated luciferase expression assay (AR-LUX) for interactive androgenic action

    NARCIS (Netherlands)

    Blankvoort, B.M.G.

    2003-01-01

    The research described in this thesis was aimed at developing an in vitro cell-based reporter gene system applicable to the detection of the illegal use of androgenic growth promoters in cattle, and the presence of potential endocrine disrupters present in surface waters and interfering with

  14. Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial.

    Science.gov (United States)

    Price, Douglas K; Chau, Cindy H; Till, Cathee; Goodman, Phyllis J; Leach, Robin J; Johnson-Pais, Teresa L; Hsing, Ann W; Hoque, Ashraful; Parnes, Howard L; Schenk, Jeannette M; Tangen, Catherine M; Thompson, Ian M; Reichardt, Juergen K V; Figg, William D

    2016-08-01

    Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment. A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. There were significant associations of genetic polymorphisms in steroid 5α-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend = .03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend = .01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend cancer risk. Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. Cancer 2016;122:2332-2340. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. 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. ...

  16. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    Science.gov (United States)

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. 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.

  18. 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

  19. 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 ...

  20. Clinical and genetic characterization of six cases with complete ...

    Indian Academy of Sciences (India)

    Themutations of androgen receptor (AR) gene are the most common cause for complete androgen insensitivity syndrome (CAIS). We aimed to characterize the six cases enrolled in our hospital (the First People's Hospital of Yunnan, China) and explore the molecular mechanism of CAIS. Between 2010 and 2013, six female ...

  1. 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.

  2. Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling.

    Science.gov (United States)

    Montt-Guevara, Maria Magdalena; Shortrede, Jorge Eduardo; Giretti, Maria Silvia; Giannini, Andrea; Mannella, Paolo; Russo, Eleonora; Genazzani, Alessandro David; Simoncini, Tommaso

    2016-01-01

    The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen 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 remodeling. 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 breast cancer treatment.

  3. Supplementation with Pfaffia glomerata (Sprengel) Pedersen does not affect androgenic-anabolic parameters in male rats.

    Science.gov (United States)

    Fernandes, Ney Felipe; Martino-Andrade, Anderson Joel; Dos Santos Lourenço, Ana Carolina; Muller, Juliane Centeno; Spercoski, Katherinne Maria; Nihi, Fabiola; Miguel, Marilis Dallarmi; de Oliveira, Vinícius Bednarczuk; Dalsenter, Paulo Roberto; Morais, Rosana Nogueira

    2015-02-23

    Paffia spp (Amaranthacea) has a widespread use of in Brazil as a possible hormonal supplement and a substitute of Panax ginseng, although information on its reproductive effects is missing. To evaluated possible anabolic-androgenic or anti-androgenic effects of Pfaffia glomerata (PG) extract using intact eight-months-old male rats and pre-pubertal castrated rats. Three different dose levels of PG (8.5, 30 and 85 mg/kg/day) were administered to eight-months-old rats for 28 days or to castrated males for 7 days (Hershberger assay). In the experiment with intact animals, 24h fecal samples were collected for quantification of fecal metabolites of androgens throughout treatment. At the end of the treatment period, animals were euthanized for evaluation of serum testosterone, reproductive organ weights, number of spermatids per testis, diameter of seminiferous tubules and cross-sectional area of soleus muscle fibers. In the Hershberber assay, androgenic or anti-androgenic effects were evaluated by the weights of androgen-dependent tissues: ventral prostate, seminal vesicle, glans penis and levator ani muscle/bulbocavernosus muscle. No effects were observed in the concentrations of fecal metabolites of androgens monitored during the treatment of intact eight-months-old rats. Moreover, at the end of treatment, no changes were seen in any of the investigated parameters. In the Hershberger assay, the PG extract did not induce androgenic or anti-androgenic effects at the dose levels tested. Significant effects were only observed in animals treated with testosterone and testosterone plus flutamide, which were used as positive controls for androgenicity and anti-androgenicity, respectively. At the dose levels tested, PG extract does not induce anabolic-androgenic or anti-androgenic effects in rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Courant Number and Mach Number Insensitive CE/SE Euler Solvers

    Science.gov (United States)

    Chang, Sin-Chung

    2005-01-01

    It has been known that the space-time CE/SE method can be used to obtain ID, 2D, and 3D steady and unsteady flow solutions with Mach numbers ranging from 0.0028 to 10. However, it is also known that a CE/SE solution may become overly dissipative when the Mach number is very small. As an initial attempt to remedy this weakness, new 1D Courant number and Mach number insensitive CE/SE Euler solvers are developed using several key concepts underlying the recent successful development of Courant number insensitive CE/SE schemes. Numerical results indicate that the new solvers are capable of resolving crisply a contact discontinuity embedded in a flow with the maximum Mach number = 0.01.

  5. Polarisation-insensitive strip-loaded waveguide for electro-optic modulators and switches

    Science.gov (United States)

    Sun, Jie; Chen, Changming; Gao, Lei; Sun, Xiaoqiang; Gao, Weinan; Ma, Chunsheng; Zhang, Daming

    2009-06-01

    A polarisation-insensitive electro-optic (EO) waveguide consisting of a dye-doped TiO2/SiO2 slab and a SU-8 strip-loaded rib is designed and fabricated. By optimizing the refractive index and size of waveguide, a trade-off between polarisation-insensitive condition and large EO efficiency (optical field interaction with the EO material) is obtained. The average transmission loss of the waveguide is less than 2.0 dB/cm. A Mach-Zehnder (M-Z) interferometer intensity modulator based on this waveguide with excellent poling stability is fabricated and measured, exhibiting 7 V half-wave voltage with 1.8 cm EO interaction length and 2.7 cm total length. This strip-loaded structure is proved to be a valuable application in EO modulators and switches.

  6. 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.

  7. 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 algorith...... was submitted to the Music Information Retrieval eXchange (MIREX) 2007 audio cover song identification task, where it came fourth of the eight submitted algorithms.......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...

  8. 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.

  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. 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

  11. 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

  12. Design methodology for understanding the sympathetic detonation characteristics of insensitive high explosives

    OpenAIRE

    Raghavan, Dinesh.

    2005-01-01

    The understanding of sympathetic detonation of energetic materials is important from the stand point of safety, shelf life, storage requirements and handling. The objective of this thesis is to introduce a methodology to assess performance and sensitivity levels of insensitive munitions to sympathetic detonations. AUTODYN code was utilized to validate the shock sensitivity results for Composition B explosives. Upon code validation, simulations were conducted to evaluate small scale sympat...

  13. Development of Environmental Health Criteria for Insensitive Munitions: Aquatic Ecotoxicological Exposures Using 2,4-Dinitroanisole

    Science.gov (United States)

    2013-03-01

    Insensitive Munitions: Aquatic Ecotoxicological Exposures Using 2,4-Dinitroanisole E nv ir on m en ta l L ab or at or y Alan J. Kennedy, Christopher... Ecotoxicological Exposures Using 2,4-Dinitroanisole Alan J. Kennedy, Jennifer G. Laird, and Sandra M. Brasfield Environmental Laboratory U.S. Army...nitroguanidine (NQ). While general aquatic ecotoxicological information is available for two of the IMX constituents (NTO and NQ), such data are not

  14. 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

  15. 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.

  16. Insensitive explosive composition and method of fracturing rock using an extrudable form of the composition

    Science.gov (United States)

    Davis, Lloyd L

    2013-11-05

    Insensitive explosive compositions were prepared by reacting di-isocyanate and/or poly-isocyanate monomers with an explosive diamine monomer. Prior to a final cure, the compositions are extrudable. The di-isocyanate monomers tend to produce tough, rubbery materials while polyfunctional monomers (i.e. having more than two isocyanate groups) tend to form rigid products. The extrudable form of the composition may be used in a variety of applications including rock fracturing.

  17. Cocaine produces conditioned place aversion in mice with a cocaine insensitive dopamine transporter

    OpenAIRE

    O’Neill, Brian; Tilley, Michael R.; Gu, Howard H.

    2012-01-01

    Cocaine is an inhibitor of the dopamine, norepinephrine, and serotonin reuptake transporters. Because its administration would therefore elevate signaling of all these three neurotransmitters, many studies have been aimed at attributing individual effects of cocaine to specific transmitter systems. Using mice with a cocaine insensitive dopamine transporter (DAT-CI mice), we previously showed that cocaine-induced dopamine elevations were necessary for its rewarding and stimulating effects. In ...

  18. Joint photomicrobial process for the degradation of the insensitive munition N-guanylurea-dinitramide (FOX-12).

    Science.gov (United States)

    Perreault, Nancy N; Halasz, Annamaria; Thiboutot, Sonia; Ampleman, Guy; Hawari, Jalal

    2013-05-21

    N-Guanylurea-dinitramide (FOX-12) is a very insensitive energetic material intended to be used in the composition of next-generation insensitive munitions. To help predict the environmental behavior and fate of FOX-12, we conducted a study to determine its photodegradability and biodegradability. When dissolved in water, FOX-12, a guanylurea-dinitramide salt, also named GUDN, dissociated instantly to produce the dinitramide moiety and guanylurea, as demonstrated by high-performance liquid chromatography (HPLC) analysis. When an aqueous solution of FOX-12 was subjected to photolysis using a solar-simulated photoreactor, we found a rapid removal of the dinitramide with concurrent formation of N₂O, NO₂(-), and NO₃(-). The second component, guanylurea, was photostable. However, when FOX-12 was incubated aerobically with the soil isolate Variovorax strain VC1 and protected from light, the dinitramide component of FOX-12 was recalcitrant but guanylurea degraded effectively to ammonia, guanidine, and presumably CO₂. When FOX-12 was incubated with strain VC1 in the presence of light, both components of FOX-12 degraded, giving similar products to those described above. We concluded that the new insensitive explosive FOX-12 can be effectively degraded by a joint photomicrobial process and, therefore, should not cause persistent contamination of surface waters.

  19. 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.

  20. Molecular analysis of pyrethroid resistance conferred by target insensitivity and increased metabolic detoxification in Plutella xylostella.

    Science.gov (United States)

    Sonoda, Shoji

    2010-05-01

    The pyrethroid resistance of the diamondback moth Plutella xylostella (L.) is conferred by increased gene expression of cytochrome P450 to detoxify the insecticide and/or through gene mutation of the sodium channel, which makes the individual insensitive to pyrethroids. However, no information is available about the correlation between the increased metabolic detoxification and the target insensitivity in pyrethroid resistance. Frequencies of pyrethroid-resistant alleles (L1014F, T929I and M918I) and two resistance-related mutations (A1101T and P1879S) at the sodium channel and expression levels of the cytochrome P450 gene CYP6BG1 were examined individually using laboratory and field strains of P. xylostella. Real-time quantitative PCR analysis using the laboratory strains revealed that levels of larval expression of the resistant strain, homozygous for the pyrethroid-resistant alleles other than the M918I, are significantly higher than those of the susceptible strain. In the field strains, the expression levels in insects having the same resistant alleles as those of the resistant strains varied greatly among individuals. The expression levels were not significantly higher than those in the heterozygotes. Significant correlation between the target insensitivity and the increased metabolic detoxification in pyrethroid resistance of P. xylostella was observed in the laboratory but not in the field.

  1. 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.

  2. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kim, Joonyoung; Jones, Lynne A.; Mercer, Nicole M.; Engelbach, John A.; Sharp, Terry L.; Welch, Michael J. E-mail: welchm@mir.wustl.edu

    2002-11-01

    PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, {sup 18}F-FDG and {sup 11}C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 {mu}g dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, n = 18), Group B (DES, no-DHT, n = 18) and Group C (DES, DHT, n = 18). In each group, 10 animals received {sup 18}F-FDG, whereas the remaining eight animals were administered {sup 11}C-acetate. Rats were sacrificed at 120 min post-injection of {sup 18}F-FDG or 30 min post-injection of {sup 11}C-acetate. Pretreatment of the mouse model using DHT (200 {mu}g of DHT in 0.1 mL of sunflower seed oil) or DES (200 {mu}g of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in {sup 18}F-FDG study, while there was no significant difference in {sup 11}C-acetate uptake. These results indicate that changes in serum testosterone levels influence {sup 18}F-FDG uptake in the prostate gland, which is closely tied to glucose

  3. Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin.

    Science.gov (United States)

    Vanky, E; Salvesen, K A; Carlsen, S M

    2004-03-01

    The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.

  4. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge

    2017-01-01

    and glucuronidase resulting in free steroids in the extract. It is well known that some sulphates are not deconjugated using aryl sulphatase; instead, for example, solvolysis can be used for deconjugation of these aliphatic sulphates. The effectiveness of solvolysis on androgenic steroid sulphates was tested...... with selected aliphatic steroid sulphates (boldenone sulphate, nortestosteron sulphate and testosterone sulphate), and the method was validated for analysis of androgenic steroids in bovine urine using free steroids, steroid sulphates and steroid glucuronides as standards. Glucuronidase and sulphuric acid......After administration of steroids to animals the steroids are partially metabolised in the liver and kidney to phase 2 metabolites, i.e., glucuronic acid or sulphate conjugates. During analysis these conjugated metabolites are normally deconjugated enzymatically with aryl sulphatase...

  5. Cortical venous thrombosis following exogenous androgen use for bodybuilding.

    Science.gov (United States)

    Sveinsson, Olafur; Herrman, Lars

    2013-02-05

    There are only a few reports of patients developing cerebral venous sinus thrombosis (CVST) after androgen therapy. We present a young man who developed cortical venous thrombosis after using androgens to increase muscle mass. He was hospitalised for parasthesia and dyspraxia in the left hand followed by a generalised tonic-clonic seizure. At admission, he was drowsy, not fully orientated, had sensory inattention, pronation drift and a positive extensor response, all on the left side. The patient had been using anabolic steroids (dainabol 20 mg/day) for the last month for bodybuilding. CT angiography showed a right cortical venous thrombosis. Anticoagulation therapy was started with intravenous heparin for 11 days and oral anticoagulation (warfarin) thereafter. A control CT angiography 4 months later showed resolution of the thrombosis. He recovered fully.

  6. Selective androgen receptor modulators in preclinical and clinical development.

    Science.gov (United States)

    Narayanan, Ramesh; Mohler, Michael L; Bohl, Casey E; Miller, Duane D; Dalton, James T

    2008-01-01

    Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on prostate and other secondary sexual organs. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, or end-stage renal disease, osteoporosis, frailty, and hypogonadism. This review summarizes the current standing of research and development of SARMs, crystallography of AR with SARMs, plausible mechanisms for their action and the potential therapeutic indications for this emerging class of drugs.

  7. Aquatic toxicity of photo-degraded insensitive munition 101 (IMX-101) constituents.

    Science.gov (United States)

    Kennedy, Alan J; Poda, Aimee R; Melby, Nicolas L; Moores, Lee C; Jordan, Shinita M; Gust, Kurt A; Bednar, Anthony J

    2017-08-01

    Insensitive munitions are desirable alternatives to historically used formulations, such as 2,4,6-trinitrotoluene (TNT), because of their so-called insensitivity to unintended detonation. The insensitive munition IMX-101 is a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). Environmental releases of munitions may be from production wastewaters or training; these munitions may be exposed to ultraviolet (UV) light. Therefore, it is useful to understand the relative toxicity of IMX-101 and its constituents both before and after photodegradation. The intent of the present study was to generate relative hazard information by exposing the standard ecotoxicological model Ceriodaphnia dubia to each insensitive munition constituent individually and to IMX-101 before and after the exposure solution was irradiated in a UV photoreactor. Without photodegradation, DNAN was more toxic (median lethal concentration [LC50] = 43 mg/L) than the other 2 constituents and it contributed predominantly to the toxicity of IMX-101 (LC50 = 206 mg/L) based on toxic units. Toxicity was observed only at high levels of NQ (LC50 = 1174 mg/L) and pH-adjusted NTO (LC50 = 799 mg/L). The toxicity of IMX-101 is lower than literature-reported TNT toxicity. Photodegradation efficiency was greater at lower insensitive munition concentrations. The observed degradation was greatest for NQ (42-99%), which in turn corresponded to the greatest relative increase in toxicity (100-1000-fold). Modest percent of degradation (4-18%) and increases in phototoxicity (2-100-fold) were observed for NTO and DNAN. Photodegraded NQ products were the predominant source of toxicity of photodegraded IMX-101. Future work involves research to enable analytical and computational confirmation of the specific degradation compounds inducing the observed photoenhanced toxicity. Environ Toxicol Chem 2017;36:2050-2057. Published 2017 Wiley Periodicals Inc. on

  8. Evaluation of androgenic activity of Mucuna pruriens in male rats ...

    African Journals Online (AJOL)

    Methanolic extract of Mucuna pruriens seed was tested for their possible androgenic activity in Wister male albino rats. The methanolic extract of M. pruriens plant was gavaged separately into 2 group of rat at similar doses of 1000 mg/kg b.wt and 1500 mg/kg b.wt for 30 days. At the end of the treatment, the animals were ...

  9. Androgen Receptor Mutations and Polymorphisms in African American Prostate Cancer

    OpenAIRE

    Koochekpour, Shahriar; Buckles, Erick; Shourideh, Mojgan; Hu, SiYi; Chandra, Dhyan; Zabaleta, Jovanny; Attwood, Kristopher

    2014-01-01

    The Androgen receptor (AR) plays a central role in the normal development of the prostate gland, in prostate carcinogenesis, and in the progression of prostate cancer (PCa) to advanced metastatic disease. African American (AA) men with PCa present with higher tumor volume, more advanced tumor stage, and higher Gleason score. This could be in part related to the AR expression or activity in the prostate tissue of AA men, or to unique mutations or polymorphisms of the AR. In Caucasian Americans...

  10. Androgen effect on body composition and fat metabolism.

    Science.gov (United States)

    Jensen, M D

    2000-01-01

    Recognizing the adverse metabolic effects of predominantly visceral body fat distribution associated with low testosterone levels, researchers have investigated the effects of androgen treatment on body fat distribution in men. This presentation reviews the results of research on acute and longer-term effects of treatment with testosterone and dihydrotestosterone. Methods for investigating these results, including measurement of lipoprotein lipase activity and of radiolabeled fat uptake and turnover, are described and discussed.

  11. Androgen receptor overexpression in prostate cancer in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Stefan Zoltán Lutz

    2018-02-01

    Conclusions: We report elevated androgen receptor signaling and activity presumably due to altered insulin/IGF-1 receptors and decreased levels of protective estrogen receptor ligands in prostate cancer in men with diabetes. Our results reveal new insights why these patients have a worse prognosis. These findings provide the basis for future clinical trials to investigate treatment response in patients with prostate cancer and diabetes.

  12. Hematopoietic androgen receptor deficiency promotes visceral fat deposition in male mice without impairing glucose homeostasis

    OpenAIRE

    Rubinow, K. B.; Wang, S.; den Hartigh, L. J.; Subramanian, S.; Morton, G. J.; Buaas, F. W.; Lamont, D.; Gray, N.; Braun, R. E.; Page, S. T.

    2015-01-01

    Androgen deficiency in men increases body fat, but the mechanisms by which testosterone suppresses fat deposition have not been elucidated fully. Adipose tissue macrophages express the androgen receptor (AR) and regulate adipose tissue remodeling. Thus, testosterone signaling in macrophages could alter the paracrine function of these cells and thereby contribute to the metabolic effects of androgens in men. A metabolic phenotyping study was performed to determine whether the loss of AR signal...

  13. Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study

    OpenAIRE

    Glaser, RL; Dimitrakakis, C; Messenger, AG

    2012-01-01

    Background Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept. Objectives To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients. Methods A total of 285 women, treated for a minimum of 1 year with subcutaneous testosterone implants for symptoms of androg...

  14. Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

    Science.gov (United States)

    2011-04-01

    androgens through de novo steroidogenesis (41–43). Xeno - graft studies have shown that knocking down AR expres- sion by shRNA could delay the progression...AD_________________ Award Number: W81XWH-08-1-0291 TITLE: Telomerase as an Androgen Receptor...March 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate

  15. Biological aspects of the potential interaction between androgen suppression and radiation therapy

    International Nuclear Information System (INIS)

    Zietman, Anthony L.

    1996-01-01

    It is a basic axiom of radiotherapy that the radiation dose required for tumor eradication increases with increasing tumor volume. These Patterns of Care Studies and prospective studies using rebiopsy have shown that this holds true for prostate cancer as well. Despite our best endeavors with conventional dose, there remains a substantial element of local failure following radiotherapy, and this is T-stage related. Unlikely many other solid tumors, a convenient method of volume reduction exists for prostate carcinoma. Approximately 90% demonstrate shrinkage following androgen suppression, an effect that is more pronounced at the primary site than metastatic sites. Transrectal ultrasound studies have shown a median of 40% prostatic tumor volume reduction after 3-4 months of androgen suppression. With more protracted androgen suppression the shrinkage progresses and a small minority of patients may actually have a complete response determined pathologically. Animal models demonstrate clearly that the TCD 50 of androgen dependent tumors may be decreased by prior androgen depression. This effect is most pronounced if radiation is deferred until the time of maximal tumor regression. The advantage is lost if the tumor is allowed to regrow in an androgen independent fashion to its original volume. It is not clear whether this benefit of neoadjuvant androgen suppression results solely from volume shrinkage. The potential for synergy exists as both radiation and androgen suppression have an element of apoptosis as a common pathway of cell death. Although apoptosis is certainly the major cause of cell death from androgen suppression its' contribution to radiation cell kill in prostatic adenocarcinomas is yet to be evaluated. If the two effects are additive and not synergistic, then sequence should be unimportant. Animal models, however, demonstrate that the TCD 50 of androgen dependent tumors is not significantly reduced by adjuvant androgen suppression. Human data is still

  16. The estrogenic and androgenic potential of pyrethroids in vitro. Review.

    Science.gov (United States)

    Saillenfait, Anne-Marie; Ndiaye, Dieynaba; Sabaté, Jean-Philippe

    2016-08-01

    Synthetic pyrethroids are used worldwide as insecticides. Their metabolites are regularly detected in the urine of adults and children from the general population. There is increasing concern that they may induce sex-hormone disrupting effects. The present work reviews available published information on the (anti)estrogenic and (anti)androgenic activity of pyrethroids in in vitro screening tests. In recent years, a large number of pyrethroids have been evaluated using various common testing methods. In tests using recombinant yeast or mammalian cells, the pyrethroids were found to be essentially negative or weakly estrogenic. More inconsistent results were found regarding their estrogenic action in proliferation tests. Conflicting findings were also reported across studies and/or assays which evaluated their anti-estrogenic or anti-androgenic potential. Some studies have suggested that certain pyrethroids may have potential antagonist activity. However, no strong interaction with the estrogenic or androgenic pathway was reported. The present review confirms the interest in performing a screening battery and in adopting an integrative approach for identifying the potential of different compounds from a chemical family to interfere with the endocrine system. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Taxifolin suppresses rat and human testicular androgen biosynthetic enzymes.

    Science.gov (United States)

    Ge, Fei; Tian, Erpo; Wang, Li; Li, Xiaoheng; Zhu, Qiqi; Wang, Yiyan; Zhong, Ying; Ge, Ren-Shan

    2018-03-01

    Taxifolin is a flavonoid. It has been used as a chemopreventive agent and supplement. It may have some beneficial effects to treat prostate cancer by suppressing androgen production in Leydig cells. The objective of the present study was to study the effects of taxifolin on androgen production of rat Leydig cells isolated from immature testis and some rat and human testosterone biosynthetic enzyme activities. Rat Leydig cells were incubated with 100μM taxifolin without (basal) or with 10ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and steroid enzyme substrates (20μM): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione. The medium concentrations of 5α-androstane-3α, 17β-diol (DIOL) and testosterone were measured. Taxifolin significantly suppressed basal, LH-stimulated, 8BR-stimulated, pregnenolone-mediated, and progesterone-mediated androgen production by Leydig cells. Further study demonstrated that taxifolin inhibited rat 3β-hydroxysteroid dehydrogenase and 17α-hydroxylase/17, 20-lyase with IC 50 values of 14.55±0.013 and 16.75±0.011μM, respectively. Taxifolin also inhibited these two enzyme activities in human testis with IC 50 value of about 100μM. Taxifolin was a competitive inhibitor for these two enzymes when steroid substrates were used. In conclusion, taxifolin may have benefits for the treatment of prostate cancer. Copyright © 2018. Published by Elsevier B.V.

  18. Androgen Receptor Genotype in Humans and Susceptibility to Endocrine Disruptors.

    Science.gov (United States)

    Lundberg Giwercman, Yvonne

    2016-01-01

    Although animal studies have raised concern that the influence of endocrine-disrupting compounds would obstruct the development of the male reproductive system, in general, exposure levels far above those found in humans have been needed to induce reproductive toxicity in animal models. Human data are inconclusive and have evoked the question whether endocrine-disrupting compounds can have any impact on hormonal function and thus health consequences when natural hormones are present. Indeed, many contaminants with hormone-like activity are much less potent than endogenous hormones themselves: 17β-oestradiol was, for instance, estimated to be 17,000 times more potent than o,p'-DDT. However, humans are exposed to a multitude of agents, and when present in sufficient number and concentration, they might in principle act collected on the actions of endogenous hormones. Whether such effects will be physiologically relevant is still not known. Nevertheless, in the worst-case scenario, there are no threshold levels below which there are no effects at all, and one target molecule is the androgen receptor. This mini review focuses on the androgen receptor gene, its link with classical endocrine disruptors and smoking, and how common genetic variants in the androgen receptor gene may influence physiological outcomes. © 2016 S. Karger AG, Basel.

  19. Minoxidil may suppress androgen receptor-related functions.

    Science.gov (United States)

    Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, An-Chi; Yang, Chih-Hsun; Chung, Wen-Hung; Wu, Wen-Guey

    2014-04-30

    Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a K(d) value of 2.6 µM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

  20. Prenatal androgen exposure and children's aggressive behavior and activity level.

    Science.gov (United States)

    Spencer, Debra; Pasterski, Vickie; Neufeld, Sharon; Glover, Vivette; O'Connor, Thomas G; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L; Hines, Melissa

    2017-11-01

    Some human behaviors, including aggression and activity level, differ on average for males and females. Here we report findings from two studies investigating possible relations between prenatal androgen and children's aggression and activity level. For study 1, aggression and activity level scores for 43 girls and 38 boys, aged 4 to 11years, with congenital adrenal hyperplasia (CAH, a genetic condition causing increased adrenal androgen production beginning prenatally) were compared to those of similarly-aged, unaffected relatives (41 girls, 31 boys). Girls with CAH scored higher on aggression than unaffected girls, d=0.69, and unaffected boys scored higher on activity level than unaffected girls, d=0.50. No other group differences were significant. For study 2, the relationship of amniotic fluid testosterone to aggression and activity level was investigated in typically-developing children (48 girls, 44 boys), aged 3 to 5years. Boys scored higher than girls on aggression, d=0.41, and activity level, d=0.50. However, amniotic fluid testosterone was not a significant predictor of aggression or activity level for either sex. The results of the two studies provide some support for an influence of prenatal androgen exposure on children's aggressive behavior, but not activity level. The within-sex variation in amniotic fluid testosterone may not be sufficient to allow reliable assessment of relations to aggression or activity level. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis.

    Science.gov (United States)

    Di Francesco, Simona; Tenaglia, Raffaele L

    2017-07-01

    Links between metabolic syndrome and prostate cancer after androgen deprivation therapy are emerging. The aim of the research was to investigate the association of metabolic syndrome and aggressive prostate malignancy, at initial diagnosis, without the influence of hormonal treatment. Retrospective analysis of 133 patients with prostate tumor diagnosis between 2007 and 2009 was conducted. Patients with prostate cancer were subdivided in 2 groups according to Gleason score: Gleason score≥7 as high-grade prostate tumor (Group 1) and Metabolic syndrome was defined according to International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute definition. Metabolic syndrome was significantly associated with aggressive prostate cancer (OR 1.87, pmetabolic syndrome were more likely to present with more aggressive prostate carcinoma vs. patients without metabolic syndrome. Further research should elucidate these relations in larger samples to confirm these associations and to stabilize future prevention and therapeutic strategies. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Steroid Androgen Exposure during Development Has No Effect on Reproductive Physiology of Biomphalaria glabrata.

    Directory of Open Access Journals (Sweden)

    Satwant Kaur

    Full Text Available Gastropod mollusks have been proposed as alternative models for male reproductive toxicity testing, due to similarities in their reproductive anatomy compared to mammals, together with evidence that endocrine disrupting chemicals can cause effects in some mollusks analogous to those seen in mammals. To test this hypothesis, we used the freshwater pulmonate snail, Biomphalaria glabrata, for which various genetic tools and a draft genome have recently become available, to investigate the effects of two steroid androgens on the development of mollusk secondary sexual organs. Here we present the results of exposures to two potent androgens, the vertebrate steroid; 5α-dihydrotestosterone (DHT and the pharmaceutical anabolic steroid; 17α-methyltestosterone (MT, under continuous flow-through conditions throughout embryonic development and up to sexual maturity. Secondary sexual gland morphology, histopathology and differential gene expression analysis were used to determine whether steroid androgens stimulated or inhibited organ development. No significant differences between tissues from control and exposed snails were identified, suggesting that these androgens elicited no biologically detectable response normally associated with exposure to androgens in vertebrate model systems. Identifying no effect of androgens in this mollusk is significant, not only in the context of the suitability of mollusks as alternative model organisms for testing vertebrate androgen receptor agonists but also, if applicable to other similar mollusks, in terms of the likely impacts of androgens and anti-androgenic pollutants present in the aquatic environment.

  3. Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

    Science.gov (United States)

    Segal, Scott; Narayanan, Ramesh; Dalton, James T

    2006-04-01

    Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

  4. 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...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  6. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Science.gov (United States)

    Altintas, Dogus Murat; Allioli, Nathalie; Decaussin, Myriam; de Bernard, Simon; Ruffion, Alain; Samarut, Jacques; Vlaeminck-Guillem, Virginie

    2013-01-01

    Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer. ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1). By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94). We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along

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

    Science.gov (United States)

    2009-12-01

    or arrest [55], and possibly in wasting diseases associated with androgen deficiency and reduced bone mass, such as HIV [56]. Anabolic steroids...controlled trial of nandrolone decanoate in HIV - infected men with mild to moderate weight loss with recombinant human growth hormone as active reference...alkaline phosphatase subclones of SaOS2 cells [121], and human osteoblastic cells [109]. However, there are also reports, in a variety of model systems

  8. Loss and recovery of androgen receptor protein expression in the adult rat testis following androgen withdrawal by ethane dimethanesulfonate.

    Directory of Open Access Journals (Sweden)

    Boycho Nikolov

    2006-06-01

    Full Text Available Androgens are especially important for the maintenance of spermatogenesis in adulthood and the experimental withdrawal of testosterone (T production by ethane dimenthanesulfonate (EDS is a valuable tool for studying androgen-dependent events of spermatogenesis. The aim of the present study was to investigate the specific changes in immunoexpression of androgen receptor (AR in the testis in relation to degeneration and regeneration of Leydig cell (LC population and seminiferous epithelium. Immunohistochemistry for AR and 3beta-hydroxysteroid dehydrogenase (3beta-HSD as well as TUNEL assay for apoptosis were performed on testicular sections of control and EDS-treated rats. Serum LH and T levels were measured by RIA. Our results revealed a total loss of AR immunoexpression from the nuclei of Sertoli (SCs, LCs and peritubular cells during the first week after EDS administration and that coincided with severe drop in T levels. Two weeks after EDS administration, the AR expression was recovered in these cells but normal stage-specificity in SCs was replaced by uniform intensity of AR immunostaining at all the stages of the spermatogenic cycle. The stage-specific pattern of androgen expression in SCs with a maximum at stages VII-VIII appeared 5 weeks after treatment. LC immunoreactivity for 3beta-HSD at different time points after EDS administration correlated with values of T concentration. The maximal germ cell apoptosis on day 7 was followed by total loss of elongated spermatids 2 weeks after EDS treatment. Regeneration of seminiferous epithelium 3 weeks after EDS administration and onwards occurred in tandem with the development of new LC population indicated by the appearance of 3beta-HSD-positive cells and gradual increase in T production. The specific changes in AR after EDS including their loss and recovery in Sertoli cells paralleled with degenerative and regenerative events in Leydig and germ cell populations, confirming close functional

  9. [3H] D-serine labels strychnine-insensitive glycine recognition sites of rat central nervous system

    International Nuclear Information System (INIS)

    Danysz, W.; Fadda, E.; Wroblewski, J.T.; Costa, E.

    1990-01-01

    In the central nervous system, glycine binds to two recognition sites; one of them (G 2 ), associated with the glutamate receptor, is insensitive to strychnine. Strychnine-insensitive sites were predominant in the forebrain areas and bound D-serine and D-alanine better than the respective L stereoisomers. [ 3 H] D-serine was a more selective radioligand than [ 3 H]glycine for the strychnine-insensitive sites. In the forebain, the binding of both ligands was inhibited by the putative G 2 receptor antagonists, 7-chlorokynurenate and 3-amino-1-hydroxy-2-pyrrolidone, while in pons and in spinal cord only the latter drug was effective. This may indicate the heterogeneity of strychnine-insensitive glycine recognition sites

  10. Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.

    Science.gov (United States)

    Turrens, J F; Bickar, D; Lehninger, A L

    1986-06-01

    The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.

  11. Evolution toward small molecule inhibitor resistance affects native enzyme function and stability, generating acarbose-insensitive cyclodextrin glucanotransferase variants

    NARCIS (Netherlands)

    Kelly, Ronan M.; Leemhuis, Hans; Gatjen, Linda; Dijkhuizen, Lubbert; Gätjen, Linda

    2008-01-01

    Small molecule inhibitors play an essential role in the selective inhibition of enzymes associated with human infection and metabolic disorders. Targeted enzymes may evolve toward inhibitor resistance through selective incorporation of mutations. Acquisition of insensitivity may, however, result in

  12. The role of disconnected and extremely insensitive parenting in the development of disorganized attachment: validation of a new measure.

    Science.gov (United States)

    Out, Dorothee; Bakermans-Kranenburg, Marian J; Van Ijzendoorn, Marinus H

    2009-09-01

    Early adverse caregiving experiences constitute an important risk factor for the development of disorganized attachment in infancy, especially extreme insensitivity and frightening behavior associated with an unresolved loss or trauma. Using existing measures for frightening parenting and disrupted communication, we developed a new measure assessing Disconnected and extremely Insensitive Parenting (DIP), in order to investigate the unique contribution of disconnected and extremely insensitive parenting behaviors to infant disorganization. Maternal behavior was assessed during a laboratory session in a low-risk sample of 202 mothers and their infants. Construct and discriminant validity of the DIP was established for both types of parental behavior. Disconnected parental behavior predicted infant disorganization but not organized attachment security, whereas extreme insensitivity was marginally related to organized attachment insecurity in boys but not to attachment disorganization.

  13. ARA24/Ran enhances the androgen-dependent NH2- and COOH-terminal interaction of the androgen receptor

    International Nuclear Information System (INIS)

    Harada, Naoki; Ohmori, Yuji; Yamaji, Ryoichi; Higashimura, Yasuki; Okamoto, Kazuki; Isohashi, Fumihide; Nakano, Yoshihisa; Inui, Hiroshi

    2008-01-01

    The androgen receptor (AR) acts as an androgen-dependent transcription factor controlling the development of prostate tissue. Upon binding to androgen, AR undergoes a dynamic structural change leading to interaction between the NH 2 - and COOH-terminal regions of AR (N-C interaction). ARA24/Ran, which is a small GTPase, functions as an AR coactivator. Here, we report that ARA24/Ran enhances the N-C interaction of AR. The constitutively GTP- or GDP-bound form of ARA24/Ran repressed the AR N-C interaction. ARA24/Ran did not enhance the transcriptional activities of AR mutants that disrupt the N-C interaction. ARA24/Ran formed an endogenous protein complex with nuclear AR, but not cytoplasmic AR. Unlike SRC-1 with the positive activity for AR N-C interaction, ARA24/Ran did not enhance the transcriptional activity of the COOH-terminal domain-deleted AR mutant that is constitutively localized in the nucleus. These data demonstrate that ARA24/Ran increases AR transactivation by enhancing the AR N-C interaction in the nucleus

  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. Hunter Syndrome

    Science.gov (United States)

    ... in girls. There's no cure for Hunter syndrome. Treatment of Hunter syndrome involves management of symptoms and complications. Symptoms Hunter syndrome is one type of a group of inherited metabolic disorders called mucopolysaccharidoses (MPSs), and Hunter syndrome is ...

  17. Contributions by the CAG-repeat Polymorphism of the Androgen Receptor Gene and Circulating Androgens to Muscle Size. Odense Androgen Study - A Population-based Study of 20-29 Year-old Danish Men

    DEFF Research Database (Denmark)

    Nielsen, Torben Leo; Hagen, Claus; Wraae, Kristian

    2007-01-01

    -29 years, who matched the background population as regards body mass index, chronic disease, medication, physical activity, smoking, and sociodemographic parameters. Genotyping was performed in 767 men, whole body DXA in 783 men, and MRI in 406 consecutively included men. Main Outcome Measures: Six......-repeat number correlated inversely with thigh and axial muscle area and with lower and upper extremity lean body mass. Except for upper extremity lean body mass, these findings remained significant in multivariate analyses controlling for circulating androgens, physical activity, smoking, alcohol intake......Context: The number of CAG-repeats within the CAG-repeat polymorphism of the androgen receptor gene is inversely correlated with the transcriptional activity of the androgen receptor. Objective: To study the effect of the CAG-repeat number and circulating androgens on muscle size, to examine...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-27

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  20. Human Adrenal Androgens: Regulation of Biosynthesis and Role in Estrogen-Responsive Breast Cancer in a Mouse Model

    National Research Council Canada - National Science Library

    Hornsby, Peter

    1997-01-01

    .... An androgen-dependent human breast cancer model was established in the scid mouse. To provide zona reticularis function, essential for adrenal androgen biosynthesis, in human adrenal organoids in the mouse, two approaches are being taken...

  1. Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

    Science.gov (United States)

    Akdoğan, Mehmet; Tamer, Mehmet Numan; Cüre, Erkan; Cüre, Medine Cumhur; Köroğlu, Banu Kale; Delibaş, Namik

    2007-05-01

    Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism. Copyright 2007 John Wiley & Sons, Ltd.

  2. IL-17A Monoclonal Antibody Partly Reverses the Glucocorticoids Insensitivity in Mice Exposed to Ozonec.

    Science.gov (United States)

    Fei, Xia; Zhang, Peng-Yu; Zhang, Xue; Zhang, Guo-Qing; Bao, Wu-Ping; Zhang, Ying-Ying; Zhang, Min; Zhou, Xin

    2017-06-01

    Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0.1 ml, respectively, for 10 times over 5 weeks. At sacrifice, lung histology, airway inflammatory cells, levels of related cytokines in bronchoalveolar lavage fluid (BALF), and serum were analyzed, airway inflammatory cell infiltration density and mean linear intercept (Lm) were measured, the expression of IL-17A mRNA, glucocorticoid receptors (GR), NF-κB, and p38 mitogen-activated protein kinase (MAPK) phosphorylation were determined. We found that combination administration markedly reduced ozone-induced total inflammatory cells, especially neutrophils; inhibited levels of cytokines, including IL-8, IL-17A, and TNF-α in BALF; and suppressed airway inflammatory cell infiltration density and Lm. Additionally, combination administration significantly elevated levels of IFN-γ in BALF, decreased the dexamethasone-induced increase of IL-17A mRNA, and increased the expression of GR and decrement of NF-κB and p38MAPK phosphorylation, which are also related to glucocorticoids insensitivity. Collectively, combination administration shows profound efficacy in inhibiting certain cytokines, and IL-17 mAb partly improved the glucocorticoids insensitivity via modulating the enhanced production rate and improving expression of IL-17A induced by glucocorticoids administration and p38MAPK, NF-κB signaling pathway.

  3. Design and performance analysis of delay insensitive multi-ring structures

    DEFF Research Database (Denmark)

    Sparsø, Jens; Staunstrup, Jørgen

    1993-01-01

    . The vector multiplier circuit has been laid out, submitted for fabrication and successfully tested. Throughout the analysis elements from this design are used to illustrate the design and performance analysis techniques. The design technique is based on a data flow approach using pipelines and rings......A set of simple design and performance analysis techniques that have been successfully used to design a number of nontrivial delay insensitive circuits is described. Examples are building blocks for digital filters and a vector multiplier using a serial-parallel multiply and accumulate algorithm...

  4. Congenital Insensitivity to Pain with Anhidrosis (CIPA Manifested with Chronic Osteomyelitis; A Case Report

    Directory of Open Access Journals (Sweden)

    Fatih Kucukdurmaz

    2014-03-01

    Full Text Available      Chronic osteomyelitis is a very rare entity among children. Also congenital insensitivity to pain with anhidrosis (CIPA is a very rare autosomal-recessive disease  of the nervous system which is one of the hereditary sensory and autonomic neuropathies (HSAN. Loss of pain, fever due to anhidrosis, recurrent fractures, chronic osteomyelitis, mental retardation, self mutilation, wound ulcers can be seen. We present a 10-year-old boy with loss of generalized pain sensation, chronic osteomyelitis on his right distal femur, bilateral corneal opacities, and decreased mental capacity.

  5. Long-Term Psychiatric and Medical Consequences of Anabolic-Androgenic Steroid Abuse

    Science.gov (United States)

    Kanayama, Gen; Hudson, James I.; Pope, Harrison G.

    2008-01-01

    Background The problem of anabolic-androgenic steroid (AAS) abuse has recently generated widespread public and media attention. Most AAS abusers, however, are not elite athletes like those portrayed in the media, and many are not competitive athletes at all. This larger but less visible population of ordinary AAS users began to emerge in about 1980. The senior members of this population are now entering middle age; they represent the leading wave of a new type of aging former substance abusers, with specific medical and psychiatric risks. Methods We reviewed the evolving literature on long-term psychiatric and medical consequences of AAS abuse. Results Long-term use of supraphysiologic doses of AAS may cause irreversible cardiovascular toxicity, especially atherosclerotic effects and cardiomyopathy. In other organ systems, evidence of persistent toxicity is more modest, and interestingly, there is little evidence for an increased risk of prostate cancer. High concentrations of AAS, comparable to those likely sustained by many AAS abusers, produce apoptotic effects on various cell types, including neuronal cells - raising the specter of possibly irreversible neuropsychiatric toxicity. Finally, AAS abuse appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood syndromes, and progression to other forms of substance abuse. However, the prevalence and severity of these various effects remains poorly understood. Conclusions As the first large wave of former AAS users now moves into middle age, it will be important to obtain more systematic data on the long-term psychiatric and medical consequences of this form of substance abuse. PMID:18599224

  6. Hamartomatous polyposis syndromes

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

    2014-01-01

    Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

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

    Science.gov (United States)

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

    2017-08-01

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

  8. Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals

    DEFF Research Database (Denmark)

    Körner, Wolfgang; Vinggaard, Anne; Terouanne, B.

    2004-01-01

    We evaluated and compared four in vitro assays to detect androgen agonists and antagonists in an international interlaboratory study. Laboratory 1 used a cell proliferation assay (assay 1) with human mammary carcinoma cells stably transfected with human androgen receptor. The other laboratories u...

  9. Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP

    NARCIS (Netherlands)

    L.J. Blok (Leen); J.E. Perry; J.K. Lindzey; D.J. Tindall; Y. Gong (Yuewen)

    1995-01-01

    textabstractElevation of intracellular calcium levels in the presence of normal androgen levels has been implicated in apoptotic prostate cell death. Since the androgen receptor (AR) plays a critical role in the regulation of growth and differentiation of the prostate, it was of

  10. Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

    Science.gov (United States)

    Low, M S Y; Vilcassim, S; Fedele, P; Grigoriadis, G

    2016-04-01

    Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians. © 2016 Royal Australasian College of Physicians.

  11. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

    Directory of Open Access Journals (Sweden)

    Tom Hildebrandt

    2018-03-01

    Full Text Available Synthetic androgens (i. e., anabolic-androgenic steroids are the primary component to the majority of problematic appearance and performance enhancing drug (APED use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc. via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  12. Penguin chicks benefit from elevated yolk androgen levels under sibling competition.

    Directory of Open Access Journals (Sweden)

    Maud Poisbleau

    Full Text Available Crested penguins (genus Eudyptes have a peculiar hatching pattern, with the first-laid egg (A-egg hatching after the second-laid egg (B-egg and chicks from A-eggs typically having a much lower survival probability. Maternal yolk androgens have been suggested to contribute to the competitive superiority of the B-chick in southern rockhopper penguins Eudyptes chrysocome, given their important role in mediating sibling competition in other species. We therefore increased the yolk androgen levels in freshly-laid eggs and examined the consequences for sibling competition--via effects on embryonic developmental times, chick growth and early survival. We placed one androgen-treated egg and one control egg into each foster nest, matching them for mass, laying date and laying order. The androgen treatment did not significantly affect embryonic developmental times or chick measurements at hatching. However, elevated yolk androgen levels benefitted chick growth in interaction with the number of siblings in a brood. Chicks from androgen-treated eggs had faster growth in the presence of a sibling than chicks from control eggs. Under these circumstances they also had a higher survival probability. Thus maternal androgens appear to reinforce the observed hatching pattern, facilitating brood reduction. This contrasts to most previous studies in other species where yolk androgens have been shown to compensate for the negative consequences of delayed hatching within the brood hierarchy.

  13. Ligand-specific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cells

    Science.gov (United States)

    Baek, Sung Hee; Ohgi, Kenneth A.; Nelson, Charles A.; Welsbie, Derek; Chen, Charlie; Sawyers, Charles L.; Rose, David W.; Rosenfeld, Michael G.

    2006-01-01

    The androgen receptor not only mediates prostate development but also serves as a key regulator of primary prostatic cancer growth. Although initially responsive to selective androgen receptor modulators (SARMs), which cause recruitment of the nuclear receptor–corepressor (N-CoR) complex, resistance invariably occurs, perhaps in response to inflammatory signals. Here we report that dismissal of nuclear receptor–corepressor complexes by specific signals or androgen receptor overexpression results in recruitment of many of the cohorts of coactivator complexes that permits SARMs and natural ligands to function as agonists. SARM-bound androgen receptors appear to exhibit failure to recruit specific components of the coactivators generally bound by liganded nuclear receptors, including cAMP response element-binding protein (CBP)/p300 or coactivator-associated arginine methyltransferase 1 (CARM1) to the SARM-bound androgen receptor, although still causing transcriptional activation of androgen receptor target genes. SARM-bound androgen receptors use distinct LXXLL (L, leucine; X, any amino acid) helices in the p160 nuclear receptor interaction domains that may impose selective allosteric effects, providing a component of the molecular basis of differential responses to different classes of ligands by androgen receptor. PMID:16492776

  14. Why do winners keep winning? Androgen mediation of winner but not loser effects in cichlid fish

    Science.gov (United States)

    Oliveira, Rui F.; Silva, Ana; Canário, Adelino V.M.

    2009-01-01

    Animal conflicts are influenced by social experience such that a previous winning experience increases the probability of winning the next agonistic interaction, whereas a previous losing experience has the opposite effect. Since androgens respond to social interactions, increasing in winners and decreasing in losers, we hypothesized that socially induced transient changes in androgen levels could be a causal mediator of winner/loser effects. To test this hypothesis, we staged fights between dyads of size-matched males of the Mozambique tilapia (Oreochromis mossambicus). After the first contest, winners were treated with the anti-androgen cyproterone acetate and losers were supplemented with 11-ketotestosterone. Two hours after the end of the first fight, two contests were staged simultaneously between the winner of the first fight and a naive male and between the loser of first fight and another naive male. The majority (88%) of control winners also won the second interaction, whereas the majority of control losers (87%) lost their second fight, thus confirming the presence of winner/loser effects in this species. As predicted, the success of anti-androgen-treated winners in the second fight decreased significantly to chance levels (44%), but the success of androgenized losers (19%) did not show a significant increase. In summary, the treatment with anti-androgen blocks the winner effect, whereas androgen administration fails to reverse the loser effect, suggesting an involvement of androgens on the winner but not on the loser effect. PMID:19324741

  15. Androgenic alopecia is not useful as an indicator of men at high risk of prostate cancer.

    NARCIS (Netherlands)

    Cremers, R.G.H.M.; Aben, K.K.H.; Vermeulen, S.; Heijer, M. den; Oort, I.M. van; Kiemeney, L.A.L.M.

    2010-01-01

    BACKGROUND: Androgens are assumed to play a central role in the pathophysiology of both prostate cancer (PC) and androgenic alopecia (AA). A correlation between the two phenotypes may be relevant for identification of men at high risk of PC. We evaluated the association between AA at different ages

  16. Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways

    Science.gov (United States)

    The focus of this meeting is the SAP's review and comment on the Agency's proposed high-throughput computational model of androgen receptor pathway activity as an alternative to the current Tier 1 androgen receptor assay (OCSPP 890.1150: Androgen Receptor Binding Rat Prostate Cyt...

  17. OM4 bend insensitive multi-mode fibers’ usefulness for MCM integration

    International Nuclear Information System (INIS)

    Guzowski, Bartłomiej; Lisik, Zbigniew; Tosik, Grzegorz; Ciupa, Emilia

    2012-01-01

    Highlights: ► The influence of high temperature exposure on OM4 fibers’ mechanical properties. ► Researching OM4 class fibers for use in innovative Optical Multi Chip Module. ► The influence of bending at a very small radius, up to 2 mm, on MM fibers. - Abstract: For future generations of electronic systems, a severe bottleneck is expected on the interconnection level and the use of optical interconnection is considered as one of the most promising solutions in this matter. Recent progress in fiber development resulted in new generation of optical fibers that are bend insensitive. This makes them ideal for Multi Chip Module (MCM) application. This paper focuses on OM4 bend insensitive multi-mode fibers’ usefulness for MCM integration, particularly the investigation of MM fiber loss is presented, which is influenced by bend diameter and the fiber's mechanical performance under influence of high temperature (400 °C–1000 °C adequate to MCM production process).

  18. A two-stage extraction procedure for insensitive munition (IM) explosive compounds in soils.

    Science.gov (United States)

    Felt, Deborah; Gurtowski, Luke; Nestler, Catherine C; Johnson, Jared; Larson, Steven

    2016-12-01

    The Department of Defense (DoD) is developing a new category of insensitive munitions (IMs) that are more resistant to detonation or promulgation from external stimuli than traditional munition formulations. The new explosive constituent compounds are 2,4-dinitroanisole (DNAN), nitroguanidine (NQ), and nitrotriazolone (NTO). The production and use of IM formulations may result in interaction of IM component compounds with soil. The chemical properties of these IM compounds present unique challenges for extraction from environmental matrices such as soil. A two-stage extraction procedure was developed and tested using several soil types amended with known concentrations of IM compounds. This procedure incorporates both an acidified phase and an organic phase to account for the chemical properties of the IM compounds. The method detection limits (MDLs) for all IM compounds in all soil types were regulatory risk-based Regional Screening Level (RSL) criteria for soil proposed by the U.S. Army Public Health Center. At defined environmentally relevant concentrations, the average recovery of each IM compound in each soil type was consistent and greater than 85%. The two-stage extraction method decreased the influence of soil composition on IM compound recovery. UV analysis of NTO established an isosbestic point based on varied pH at a detection wavelength of 341 nm. The two-stage soil extraction method is equally effective for traditional munition compounds, a potentially important point when examining soils exposed to both traditional and insensitive munitions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Insensitive high-energy energetic structural material of tungsten-polytetrafluoroethylene-aluminum composites

    Directory of Open Access Journals (Sweden)

    Liu Wang

    2015-11-01

    Full Text Available Energetic structural material is a kind of materials that are inert under normal conditions but could produce exothermic chemical reaction when subjected to impact. This report shows a kind of energetic structural material of tungsten (W-polytetrafluoroethylene (PTFE-aluminum (Al with density of 4.12 g/cm3, excellent ductility and dynamic compressive strength of 96 MPa. Moreover, 50W-35PTFE-15Al (wt% can exhibit a high reaction energy value of more than 2 times of TNT per unit mass and 5 times of TNT per unit volume, respectively, but with excellent insensitivity compared with traditional explosives. Under thermal conditions, the W-PTFE-Al composite can keep stable at 773 K. Under impact loading, when the strain rate up to ∼4820 s−1 coupled with the absorbed energy per unit volume of 120 J/cm3, deflagration occurs and combustion lasts for 500 μs. During impact compressive deformation, the PTFE matrix is elongated into nano-fibers, thus significantly increases the reaction activity of W-PTFE-Al composites. The nano-fiber structure is necessary for the reaction of W-PTFE-Al composites. The formation of PTFE nano-fibers must undergo severe plastic deformation, and therefore the W-PTFE-Al composites exhibit excellent insensitivity and safety. Furthermore, the reaction mechanisms of W-PTFE-Al composites in argon and in air are revealed.

  20. A Robust, Gravity-Insensitive, High-Temperature Condenser for Water Recovery

    Science.gov (United States)

    Chen, Weibo; Conboy, Thomas; Ewert, Michael

    2016-01-01

    Regenerative life support systems are vital for NASA's future long-duration human space exploration missions. A Heat Melt Compactor (HMC) system is being developed by NASA to dry and compress trash generated during space missions. The resulting water vapor is recovered and separated from the process gas flow by a gravity-insensitive condenser. Creare is developing a high-temperature condenser for this application. The entire condenser is constructed from metals that have excellent resistance to chemical attack from contaminants and is suitable for high-temperature operation. The metal construction and design configuration also offer greatest flexibility for potential coating and regeneration processes to reduce biofilm growth and thus enhancing the reliability of the condenser. The proposed condenser builds on the gravity-insensitive phase separator technology Creare developed for aircraft and spacecraft applications. This paper will first discuss the design requirements for the condenser in an HMC system that will be demonstrated on the International Space Station (ISS). Then, it will present the overall design of the condenser and the preliminary thermal test results of a subscale condenser. Finally, this paper will discuss the predicted performance of the full-size condenser and the development plan to mature the technology and enhance its long-term reliability for a flight system.

  1. Biochemical characterization of trinitrotoluene transforming oxygen-insensitive nitroreductases from Clostridium acetobutylicum ATCC 824.

    Science.gov (United States)

    Kutty, Razia; Bennett, George N

    2005-11-01

    The genes that encode oxygen-insensitive nitroreductases from Clostridium acetobutylicum possessing 2,4,6-Trinitrotoluene (TNT) transformation activity were cloned, sequenced and characterized. The gene products NitA (MW 31 kDa) and NitB (MW 23 kDa) were purified to homogeneity. The NitA and NitB are oxygen-insensitive nitroreductases comprised of a single nitroreductase domain. NitA and NitB enzymes show spectral characteristics similar to flavoproteins. The biochemical characteristics of NitA and NitB are highly similar to those of NfsA, the major nitroreductase from E. coli. NitA exhibited broad specificity similar to that of E. coli NfsA and displayed no flavin reductase activity. NitB showed broad substrate specificity toward nitrocompounds in a pattern similar to NfsA and NfsB of Escherichia coli. NitB has high sequence similarity to NAD(P)H nitroreductase from Archaeoglobus fulgidus. NitA could utilize only NADH as an electron donor, whereas NitB utilized both NADH and NADPH as electron donors with a preference for NADH. The activity of both nitroreductases was high toward 2,4-Dinitrotoluene (2,4-DNT) as a substrate. Both the nitroreductases were inhibited by dicoumarol and salicyl hydroxamate. The nitroreductases showed higher relative expression on induction with TNT, nitrofurazone and nitrofurantoin compared to the uninduced control.

  2. The rotenone-insensitive reduction of quinones and nitrocompounds by mitochondrial NADH:ubiquinone reductase.

    Science.gov (United States)

    Bironaite, D A; Cenas, N K; Kulys, J J

    1991-10-18

    The rotenone-insensitive reduction of quinones and aromatic nitrocompounds by mitochondrial NADH: ubiquinone reductase (complex I, EC 1.6.99.3) has been studied. It was found that these reactions proceed via a mixed one- and two-electron transfer. The logarithms of the bimolecular rate constants of oxidation (TN/Km) are proportional to the one-electron-reduction potentials of oxidizers. The reactivities of nitrocompounds are close to those of quinones. Unlike the reduction of ferricyanide, these reactions are not inhibited by NADH. However, they are inhibited by NAD+ and ADP-ribose, which also act as the mixed-type inhibitors for ferricyanide. TN/Km of quinones and nitrocompounds depend on the NAD+/NADH ratio, but not on NAD+ concentration. They are diminished by the limiting factors of 2.5-3.5 at NAD+/NADH greater than 200. It seems that rotenone-insensitive reduction of quinones and nitrocompounds takes place near the NAD+/NADH and ferricyanide binding site, and the inhibition is caused by induced conformational changes after the binding of NAD+ or ADP-ribose.

  3. Concentration-insensitive phosphorescent organic light emitting devices (PhOLEDs) for easy manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Dumur, Frédéric, E-mail: frederic.dumur@univ-amu.fr [Aix-Marseille Université, CNRS, ICR, UMR 7273, F-13397 Marseille (France); Lepeltier, Marc [Institut Lavoisier de Versailles, UMR 8180 CNRS, Université de Versailles Saint-Quentin en Yvelines, 45 avenue des Etats-Unis, 78035 Versailles Cedex (France); Zamani Siboni, Hossein, E-mail: hzamanis@uwaterloo.ca [Department of Electrical and Computer Engineering, University of Waterloo, 200 University Avenue West Waterloo, ON, Canada N2L 3G1 (Canada); Xiao, Pu; Graff, Bernadette; Lalevée, Jacques [Institut de Science des Matériaux de Mulhouse IS2M, UMR 7361 CNRS, Université de Haute Alsace, 15 rue Jean Starcky, 68057 Mulhouse Cedex (France); Gigmes, Didier [Aix-Marseille Université, CNRS, ICR, UMR 7273, F-13397 Marseille (France); Aziz, Hany [Department of Electrical and Computer Engineering, University of Waterloo, 200 University Avenue West Waterloo, ON, Canada N2L 3G1 (Canada)

    2014-07-01

    Two heteroleptic iridium(III) complexes Ir(piq){sub 2}(dbm) and Ir(btp){sub 2}(acac) have been tested as emitters for phosphorescent OLEDs (PhOLEDs). Interestingly, device performance exhibited a marked insensitivity to the dopant concentration. In this study, a dibenzoylmethane (dbm)-based complex has also been tested for the first time as dopant for OLEDs. To evaluate the emissive properties of this new emitter belonging to a family of complexes that has not been investigated yet, identical devices were prepared with the well-known red dopant Ir(btp){sub 2}(acac) for comparison. The new complex Ir(piq){sub 2}(dbm) exhibited comparable performance to that obtained with Ir(btp){sub 2}(acac). - Highlights: • A new neutral iridium complex has been tested as emitter. • TD-DFT calculations and electrochemical measurements were carried out to support the experimental results. • UV–visible absorption and photoluminescence spectroscopy of complexes were investigated. • Concentration-insensitive phosphorescent organic light emitting devices were obtained.

  4. Divalent phosphate is a counterion for carboxyatractyloside-insensitive adenine nucleotide transport in rat liver mitochondria

    International Nuclear Information System (INIS)

    Nosek, M.T.; Aprille, J.R.

    1986-01-01

    Unidirectional, carboxyatractyloside(CAT)-insensitive adenine nucleotide (AdN) fluxes have been studied in isolated rat liver mitochondria (mito). Previous work has shown that ATP x Mg transport in one direction is coupled to ATP x Mg or P/sub i/ transport in the opposite direction. The purpose of this study was to determine whether divalent HPO 4 2- or monovalent H 2 PO 4 - is the transported phosphate species. The authors used the monofluorophosphate (PO 3 F 2- ) and difluorophosphate (PO 2 F 2 - ) analogues as potential counterions forAdN efflux. After a preincubation on ice with 14 C-ADP to label the matrix AdN, efflux was measured at 30 0 C, pH 7.4, in 225mM sucrose, 10mM KCl, 5mM MgCl 2 , 5mM glutamate, 5mM malate, 10mM Tris, 0.5mM P/sub i/, 1mM ATP, and 5μM CAT. With no other additions efflux was -0.62 +/- 0.20 nmole/minute/mg protein. The data supports the hypothesis that divalent but not monovalent phosphate can act as a counterion for ATPx Mg transport over this CAT-insensitive carrier

  5. Ultrathin triple-band polarization-insensitive wide-angle compact metamaterial absorber

    International Nuclear Information System (INIS)

    Shang, Shuai; Yang, Shizhong; Tao, Lu; Yang, Lisheng; Cao, Hailin

    2016-01-01

    In this study, the design, realization, and characterization of an ultrathin triple-band polarization-insensitive wide-angle metamaterial absorber are reported. The metamaterial absorber comprises a periodic array of modified six-fold symmetric snowflake-shaped resonators with strip spiral line load, which is printed on a dielectric substrate backed by a metal ground plane. It is shown that the absorber exhibits three distinct near-unity absorption peaks, which are distributed across C, X, Ku bands, respectively. Owing to the six-fold symmetry, the absorber is insensitive to the polarization of the incident radiation. In addition, the absorber shows excellent absorption performance over wide oblique incident angles for both transverse electric and transverse magnetic polarizations. Simulated surface current and field distributions at the three absorption peaks are demonstrated to understand the absorption mechanism. Particularly, the absorption modes come from the fundamental and high-order dipole resonances. Furthermore, the experimental verification of the designed absorber is conducted, and the measured results are in reasonable agreement with the simulated ones. The proposed ultrathin (∼0.018λ 0 , λ 0 corresponding to the lowest peak absorption frequency) compact (0.168λ 0 ×0.168λ 0 corresponding to the area of a unit cell) absorber enables potential applications such as stealth technology, electromagnetic interference and spectrum identification.

  6. Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides

    International Nuclear Information System (INIS)

    Monaco, M.E.

    1987-01-01

    Previous studies have indicated the existence of two separate pools of phosphoinositides in WRK-1 cells; one is labile and hormone-sensitive with respect to turnover, while the other is stable. Hormonal stimulation results in a rapid increase in 32 Pi incorporation into the sensitive pool, while in the absence of hormone, incorporation of 32 Pi into this pool is slow. Results are quite different when [ 3 H]inositol is the precursor utilized. Incorporation of [ 3 H]inositol into hormone-sensitive phosphoinositides is not stimulated in the presence of hormone, suggesting entry of this exogenous precursor into the cycle by a route other than the resynthetic phase of the cycle. Furthermore, failure of hormone to induce loss of [ 3 H]phosphoinositide in pulse-chase experiments in the absence of lithium suggests reutilization of the [ 3 H]inositol moiety generated by phosphodiesteratic cleavage of hormone-sensitive phosphoinositide. Time course studies indicate that the relative rates of incorporation of [ 3 H]inositol into sensitive and insensitive phosphoinositide remain constant from 2 to 24 h. Several factors are capable of increasing [ 3 H]inositol incorporation into hormone-insensitive phosphoinositide including vasopressin, calcium ionophores, and manganese. On the other hand, vasopressin treatment appears to decrease incorporation of [ 3 H]inositol into the hormone-sensitive pool, probably by shifting the equilibrium between phosphoinositides and inositol phosphates, since the decrease in radioactivity observed in the phosphoinositides is equaled by the increase observed in that in the inositol phosphates

  7. Androgen-Dependent Regulation of Human MUC1 Mucin Expression

    Directory of Open Access Journals (Sweden)

    Stephen Mitchell

    2002-01-01

    Full Text Available MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor. (20AR activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1protein expression: 1 AR+MUCi + [DAR17+19. (20AR transfectants of DU-145, ZR-75-1, MDA-MB-453, and T47D]; 2 AR-MUCi+ [DZeoi. (20AR- vector control, DU-145, BT20, MDA-MB231, and MCF7]; 3 AIR +MUCi -. (20LNCaP and LNCaP-r. Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 pM to 1 µM. Cell surface MUC1expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide. (204-OH, a nonsteroidal AR antagonist. The functional significance of MUC1expression was investigated with a cell-cell aggregation assay. Only AR+ MUC1 + cell lines showed a significant increase in MUC1expression with AR activation. (20P. (20range =.01 to .0001, reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1was associated with a significant. (20P. (20range =.002 to .001 reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.

  8. Androgenic alopecia and dutasteride in hair mesotherapy: A short review

    Directory of Open Access Journals (Sweden)

    Estela B Busanello

    2018-02-01

    Full Text Available Androgenic alopecia (AGA is the most common cause of patterned hair loss in predisposed men and women. AGA is a multifactorial and polygenetic condition, affecting up to 80% of men and 40-50% of women during life. AGA is characterized by a gradual reduction of the anagen and increase in telagen phase, leading to a progressive follicle miniaturization. As a consequence, terminal hairs are converted into vellus hairs decreasing hair density. The pathophysiology of AGA is heterogeneous and highly complex. A diverse combination of genetical factors, endocrine abnormalities, circulating androgens, drugs, diet and microinflammation in hair follicles of each individual are related to this condition. However, it is well known that androgens are the major modulators of male AGA but their specific action on female AGA is still under debate. Circulating testosterone is converted by 5a-reductase in 5a-dihydrotestosterone (DHT in the periphery, a decrease of anagen phase occur, anticipating catagen phase in a complex process involving apoptosis as probably microinflammation. In AGA treatment, mesotherapy is being used with 5a-reductase inhibitors, especially dutasteride, injected directly on scalp. Thus, this updated review summarized the injectable use of dutasteride based on data available on PubMed until March 2017. Dutasteride, a second-generation inhibitor of 5a-reductase is more potent than finasteride due to the capability of inhibit types 1 and 2 of the enzyme. The efficacy and safety of hair mesotherapy with dutasteride were reported by distinct groups and the best results were achieved when this compound was used in combination with other substances, increasing hair growth. This result could be explained by the multifactorial pathophysiology of AGA, involving hair follicle sensitivity to DHT and microinflammation. Therefore, a multi-therapeutic approach seems to be more effective in AGA management. In conclusion, more studies are needed to

  9. Androgen status in healthy premenopausal women with loss of libido.

    Science.gov (United States)

    Nyunt, A; Stephen, G; Gibbin, J; Durgan, L; Fielding, A M; Wheeler, M; Price, D E

    2005-01-01

    Androgen deficiency may contribute to female sexual dysfunction and loss of libido. The role of the active metabolite of testosterone, dihydrotestosterone (DHT), in these conditions is uncertain. The aim of this study was to determine the role of androgens and DHT in the etiology of loss of libido in healthy women. We studied 29 premenopausal women with reduced libido (subjects) and 12 healthy females (controls). They were aged 18 to 45 years and in a stable heterosexual relationship. At 9 a.m. we took venous blood in the follicular phase for serum estradiol, total testosterone, and DHT, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels. Subjects were interviewed by a psychosexual counsellor. Using the modified Wilson's sexual fantasy questionnaire (Baumgartner, Scalora, & Huss, 2002) and sexual satisfaction by Golombok-Rust Inventory of Sexual Satisfaction (GRISS Rust & Golombok, 1985, 1986) we assessed sexual drive. The total testosterone and DHT levels (mean +/- SD) were respectively 0.97 +/- 0.38 mmol/L and 0.76 +/- 0.37 nmol/L in subjects and 0.97 +/- 0.41 mmol/L and 0.77 +/- 0.15 nmol/L in controls. The SHBG and DHEAS were respectively 65 +/- 42 mmol/L and 3.76 +/- 1.0 umol/L in subjects and 65 +/- 29 mmol/L and 3.67 +/- 2.6 in controls. The scores of the Wilson questionnaire and GRISS were respectively 21 +/- 14.1 and 5 +/- 2.1 in subjects and 35 +/- 14.8 & 2 +/- 1.2 in controls. Subjects were more likely than controls to have low income (48% versus 8%, p libido in otherwise healthy women may be related to relationship problem, depression, psychosocial factors, and sexual dysfunction in the partner but do not appear to be related to androgen status.

  10. The androgen receptor as an emerging target in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kanda T

    2015-06-01

    Full Text Available Tatsuo Kanda, Osamu Yokosuka Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan Abstract: Hepatocellular carcinoma (HCC is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase–, v-akt murine thymoma viral oncogene homolog 1–, or signal-transducer and activator of transcription–signaling pathway, which has been implicated in the development of HCC. It has been reported that more than 200 RNA expression levels are altered by androgen treatment. In the liver, androgen-responsive genes are cytochrome P450s, transforming growth factor , vascular endothelial growth factor, and glucose-regulated protein 78 kDa, which are also associated with human hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell migration and metastasis. It is possible that cross-talk among AR-signaling, endoplasmic reticulum stress, and innate immune response is important for human hepatocarcinogenesis and HCC development. This review shows that AR could play a potential role in human HCC and represent one of the important target molecules for the treatment of HCC. Keywords: vascular endothelial growth factor, angiogenesis, glucose-regulated protein 78 kDa, hepatocarcinogenesis, molecular targets 

  11. Platelet-Rich Plasma in Androgenic Alopecia: Indications, Technique, and Potential Benefits.

    Science.gov (United States)

    Ferneini, Elie M; Beauvais, Daniel; Castiglione, Concetta; Ferneini, Moniek V

    2017-04-01

    The purpose of this study was to provide an overview of platelet-rich plasma (PRP) injected into the scalp for the management of androgenic alopecia. A literature review was performed to evaluate the benefits of PRP in androgenic alopecia. Hair restoration has been increasing. PRP's main components of platelet-derived growth factor, transforming growth factor, and vascular endothelial growth factor have the potential to stimulate hard and soft tissue wound healing. In general, PRP showed a benefit on patients with androgenic alopecia, including increased hair density and quality. Currently, different PRP preparations are being used with no standard technique. This review found beneficial effects of PRP on androgenic alopecia. However, more rigorous study designs, including larger samples, quantitative measurements of effect, and longer follow-up periods, are needed to solidify the utility of PRP for treating patients with androgenic alopecia. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Is there a correlation between androgens and sexual desire in women?

    DEFF Research Database (Denmark)

    Wåhlin-Jacobsen, Sarah; Pedersen, Anette Tønnes; Kristensen, Ellids

    2015-01-01

    INTRODUCTION: For women, the correlation between circulating androgens and sexual desire is inconclusive. Substitution with androgens at physiological levels improves sexual function in women who experience decreased sexual desire and androgen deficiency from surgical menopause, pituitary disease...... between serum levels of androgens and sexual desire in women and whether the level of ADT-G is better correlated than the level of circulating androgens with sexual desire. METHODS: This was a cross-sectional study including 560 healthy women aged 19-65 years divided into three age groups. Correlations...... were considered to be statistically significant at PSexual desire was determined as the total score of the sexual desire domain of the Female Sexual Function Index. Total testosterone (TT), calculated free testosterone (FT), androstenedione, dehydroepiandrosterone sulfate...

  13. Ekspresi Gen CYP19 Aromatase, Estrogen, Androgen pada penderita Periodontitis Agresif

    Directory of Open Access Journals (Sweden)

    Dahlia Herawati

    2016-11-01

    Full Text Available Kepadatan tulang tubuh ditentukan oleh gen CYP19 aromatase, hormon estrogen dan androgen. Pada periodontitis agresif terjadi perkembangan cepat kerusakan tulang alveolar, dan kerusakan tulang alveoler tersebut tidak diimbangioleh regenerasi tulang. Tujuan penelitian ini adalah menunjukkan ekspresi gen CYP19 aromatase, estrogen, androgen pada penderita periodontitis agresif agar dapat untuk menjadi pertimbangan pada saat melakukan perawatan periodontal. Metode penelitian, pemeriksaan ekspresi gen aromatse CYP19 berasal dari spesimen tulang alveolar menggunakan imunohistokimia, pengukuran hormon estrogen dan androgen dari serum menggunakan Vidas: Elfa. Hasil penelitian ekspresi gene CYP19 aromatase pada periodontitis agresif menunjukkan gambaran lebih rendah densitasnya dibandingkan pada nonperiodontitis. Estrogen dan androgen pad aperiodontitis agresif ada kecenderungan lebih rendah dibandingkan pada nonperiodontitis. Kesimpulan regenerasi tulang alveoler pad a periodontitis agresif terhambat karena sedikitnya gen CYP19 aromatase dan hormon estrogen dan androgen yang berperan pada pembentukan tulang alveoler kurang memadai.

  14. Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

    Directory of Open Access Journals (Sweden)

    Manal K. Al Kindi

    2012-11-01

    Full Text Available Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosteronein females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG, free androgen index (FAI, and calculated free testosterone (CFT in the assessment of androgen status in women investigated for suspected hyperandrogenism.Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18. The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19, hirsutism (group 3; n=18, menstrual disturbances (irregularities or infertility (group 4; n=49, as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5;n=18. Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation.Results: There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73

  15. Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

    Science.gov (United States)

    Al Kindi, Manal K.; Al Essry, Faiza S.; Al Essry, Fatma S.; Mula-Abed, Waad-Allah S.

    2012-01-01

    Objectives There are technical limitations for the currently available methods of measuring serum total and free testosterone in females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), and calculated free testosterone (CFT) in the assessment of androgen status in women investigated for suspected hyperandrogenism. Methods This is a case control study that was conducted during the period from 1st May 2011 to 31st October 2011 on 122 patients aged (18-45 years) whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls (group 1; n=18). The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome (PCOS [group 2; n=19), hirsutism (group 3; n=18), menstrual disturbances (irregularities) or infertility (group 4; n=49), as well as combination of PCOS or hirsutism and menstrual disturbances or infertility (group 5; n=18). Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation. Results There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG 5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73

  16. In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA

    DEFF Research Database (Denmark)

    Nielsen, M. E.; Rasmussen, I. A.; Kristensen, Stine Gry

    2011-01-01

    RNA analysis (24 women). Expression of Androgen Receptor (AR) mRNA levels in granulosa cells, and of androstenedione and testosterone in FF, were correlated to the expression of FSH receptor (FSHR), LH receptor (LHR), CYP19 and anti-Müllerian Hormone-receptor2 (AMHR2) mRNA in the granulosa cells and to the FF....... This suggests that follicular sensitivity towards FSH stimulation may be augmented by stimulation of androgens via the AR....

  17. Lepidium meyenii (Maca) does not exert direct androgenic activities.

    Science.gov (United States)

    Bogani, P; Simonini, F; Iriti, M; Rossoni, M; Faoro, F; Poletti, A; Visioli, F

    2006-04-06

    Maca is the edible root of the Peruvian plant Lepidum meyenii, traditionally employed for its purported aphrodisiac and fertility-enhancing properties. This study aimed at testing the hypothesis that Maca contains testosterone-like compounds, able to bind the human androgen receptor and promote transcription pathways regulated by steroid hormone signaling. Maca extracts (obtained with different solvents: methanol, ethanol, hexane and chloroform) are not able to regulate GRE (glucocorticoid response element) activation. Further experiments are needed to assess which compound, of the several Maca's components, is responsible of the observed in vivo effects.

  18. Identification of novel androgen receptor target genes in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gerald William L

    2007-06-01

    Full Text Available Abstract Background The androgen receptor (AR plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa. However, little is known about AR target genes that mediate the receptor's roles in disease progression. Results Using Chromatin Immunoprecipitation (ChIP Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant and LNCaP (androgen-dependent PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells – D-dopachrome tautomerase (DDT, Protein kinase C delta (PRKCD, Glutathione S- transferase theta 2 (GSTT2, Transient receptor potential cation channel subfamily V member 3 (TRPV3, and Pyrroline-5-carboxylate reductase 1 (PYCR1 – most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT, was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation. Conclusion AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are

  19. 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......, determined in the presence of increasing concentrations of R1881. No cytotoxic effects of the tested compounds were observed as determined either by metabolic reduction using AlamarBlue (up to 20 mu M) or determined in cells transfected with a constitutively active hAR (up to 10 mu M). The well-known ability...

  20. Gingival fibromatosis with hypertrichosis syndrome: Case series of rare syndrome

    Directory of Open Access Journals (Sweden)

    Preetha Balaji

    2017-01-01

    Full Text Available Gingival fibromatosis with hypertrichosis syndrome is an extremely rare genetic condition characterized by profound overgrowth of hair and gums, as well as other variable features. Gingival fibromatosis is characterized by a large increase in the gingival dimension which extends above the dental crowns, covering them partially or completely. They were found to have a genetic origin, may also occur in isolation or be part of a syndrome, or acquired origin, due to specific drugs administered systemically. Congenital generalized hypertrichosis is a heterogeneous group of diseases with continuing excessive growth of terminal hair without androgenic stimulation. It has informally been called werewolf syndrome because the appearance is similar to that of a werewolf. Various syndromes have been associated with these features such as epilepsy, mental retardation, cardiomegaly, or osteochondrodysplasia. As so far very few cases have been reported in literature, we are reporting a series of three cases with management of the same. The excess gingival tissues, in these cases, were removed by conventional gingivectomy under general anesthesia. The postoperative result was uneventful and the patient's appearance improved significantly. Good esthetic result was achieved to allow patient to practice oral hygiene measures. Though this is not a serious condition clinically, psychosocial trauma cannot be neglected owing to the cosmetic disfigurement it produces.