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Testosterone receptor

Giuseppe Loverro, Leonardo Resta, Miriam Dellino, Di Naro Edoardo, Maria Arcangela Cascarano, Matteo Loverro, Salvatore Andrea Mastrolia
OBJECTIVE: Female-to-male transition remains a specific clinical indication for long-term testosterone administration. There is a limited number of studies dealing with the effect of androgen treatment on their female receptive targets (mainly breast and uterus) and the knowledge in this field is scarce and, sometimes, contradictory. MATERIALS AND METHODS: We performed a prospective study including 12 patients aged between 20 years and 32 years, with a diagnosis of gender dysphoria, treated with parenteral testosterone administration before sexual reassignment surgery...
October 2016: Taiwanese Journal of Obstetrics & Gynecology
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
October 6, 2016: Psychoneuroendocrinology
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Maria Magdalena Montt-Guevara, Jorge Eduardo Shortrede, Maria Silvia Giretti, Andrea Giannini, Paolo Mannella, Eleonora Russo, Alessandro David Genazzani, Tommaso Simoncini
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...
2016: Frontiers in Endocrinology
Wararut Buncharoen, Kanokporn Saenphet, Supap Saenphet, Chatchote Titaram
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine has used Uvaria rufa Blume as an ethnomedicinal plant for treating fever, skin allergies, intestinal ulcers and prostate disorders including BPH. However, no scientific evidence supports the traditional use. AIM OF THE STUDY: This study aimed to evaluate the therapeutic potential of U. rufa on BPH using in vitro and in vivo models. MATERIALS AND METHODS: In vitro studies screened the efficacy of a 5α-reductase (5αR) inhibition and antioxidant activity of petroleum ether, ethyl acetate, ethanol and aqueous extracts from the stem of U...
October 9, 2016: Journal of Ethnopharmacology
Yadanar Moe, Chaw Kyi-Tha-Thu, Tomoko Tanaka, Hiroto Ito, Satowa Yahashi, Ken-Ichi Matsuda, Mitsuhiro Kawata, Goro Katsuura, Fumihiro Iwashige, Ichiro Sakata, Atsushi Akune, Akio Inui, Takafumi Sakai, Sonoko Ogawa, Shinji Tsukahara
We found a novel sexually dimorphic area in the dorsal hypothalamus of mice (hereafter the SDA-DH). The SDA-DH was sandwiched between two known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal cell density. The density of neurons in the SDA-DH was increased in male mice by orchidectomy on the day of birth and decreased in female mice by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth...
October 11, 2016: Endocrinology
Min Jae Kang, Jeong Seon Lee, Hwa Young Kim, Hae Woon Jung, Young Ah Lee, Sun Hee Lee, Ji-Young Seo, Jae Hyun Kim, Hye Rim Chung, Se Young Kim, Choong Ho Shin, Sei Won Yang
The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled...
October 6, 2016: Endocrine Journal
Edgar Flores-Soto, Jorge Reyes-García, Abril Carbajal-García, Elías Campuzano-González, Mercedes Perusquía, Bettina Sommer, Luis M Montaño
: Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17β-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca(2+) channel (L-VDCC, D-600) and store operated Ca(2+) channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca(2+) concentrations (b[Ca(2+)]i) as D-600+2-APB but to a higher extend...
October 4, 2016: Molecular and Cellular Endocrinology
Rebecca Milsk, Jenna E Cavallin, Elizabeth J Durhan, Kathleen M Jensen, Michael D Kahl, Elizabeth A Makynen, Dalma Martinović-Weigelt, Nathan Mueller, Anthony Schroeder, Daniel L Villeneuve, Gerald T Ankley
The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnows (Pimephales promelas) treated with the model androgen receptor (AR) antagonist flutamide. Reproductively-mature fish were exposed in a flow-through test to analytically-confirmed concentrations of either 50 or 500μg flutamide/L for 8 d, followed by an 8-d recovery period in clean water. Fish were sampled at 1, 2, 4 and 8days during each phase of the experiment. Flutamide (500μg/L) caused significant reductions in relative gonad size of the females on day 8 of the exposure and day 1 of the recovery, and reduced expression of secondary sex characteristics in males during the exposure phase of the experiment...
October 1, 2016: Aquatic Toxicology
Yufeng Gong, Hua Tian, Yifei Dong, Xiaona Zhang, Wei Wang, Shaoguo Ru
Refuse leachate is likely an important source of androgens. However, common in vitro bioassays underestimate the potential androgenic activity of leachate, owing to non-receptor-mediated mechanisms that modify the balance of sex hormones and promote the accumulation of endogenous androgens. This study aimed to develop an in vivo assay by using multiple biomarkers related to testosterone synthesis and conversion for assessing the potential androgenic activity of refuse leachate sampled from a municipal solid waste treatment plant in Qingdao, China...
October 4, 2016: Ecotoxicology and Environmental Safety
Nur-Vaizura Mohamad, Ima-Nirwana Soelaiman, Kok-Yong Chin
Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts...
2016: Clinical Interventions in Aging
Christoph Eisenegger, Robert Kumsta, Michael Naef, Jörg Gromoll, Markus Heinrichs
A contribution to a special issue on Hormones and Human Competition Studies in non-human animals and humans have demonstrated the important role of testosterone in competitive interactions. Here, we investigated whether endogenous testosterone levels predict the decision to compete, in a design excluding spite as a motive underlying competitiveness. In a laboratory experiment with real monetary incentives, 181 men solved arithmetic problems, first under a noncompetitive piece rate, followed by a competition incentive scheme...
October 1, 2016: Hormones and Behavior
Lixian Cheng, Hui Shi, Yan Jin, Xiaoxi Li, Jinshun Pan, Yimei Lai, Yan Lin, Ya Jin, Gaurab Roy, Allan Zhao, Fanghong Li
Adipose tissue plays an important role in regulating female fertility owing to not only its energy stores but also the endocrine actions of secreted adipokines. As one of the adipokines, adiponectin is almost exclusively secreted from the fat and its circulating concentration is paradoxically reduced in obesity. Although recent studies implied a purported positive role of adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed subfertility in female adiponectin null mice, and therefore postulated a protective role of adiponectin in ovarian functions...
October 4, 2016: Endocrinology
Bo Huang, Ryan Butler, Yifei Miao, Yubing Dai, Wanfu Wu, Wen Su, Yoshiaki Fujii-Kuriyama, Margaret Warner, Jan-Åke Gustafsson
The aryl hydrocarbon receptor (AhR) is now recognized as an important physiological regulator in the immune and reproductive systems, and in the development of the liver and vascular system. AhR regulates cell cycle, cell proliferation, and differentiation through interacting with other signaling pathways, like estrogen receptor α (ERα), androgen receptor (AR), and Notch signaling. In the present study, we investigated Notch and estrogen signaling in AhR(-/-) mice. We found low fertility with degenerative changes in the testes, germ cell apoptosis, and a reduced number of early spermatids...
September 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
Shubo Jin, Dajiang Sun, Qingkai Xi, Xiaoli Dong, Dan Song, Hongtuo Fu, Ying Zhang
Kisspeptin plays an important role in the reproduction and onset of puberty in vertebrates through stimulation of gonadotropin-releasing hormone (GnRH). However, the mechanisms whereby kisspeptin-related genes regulate sexual differentiation in teleosts are poorly understood. We aimed to study the relationship between the hypothalamus-pituitary-gonad (HPG) axis and sexual differentiation in relation to kisspeptin in the sturgeon Acipenser schrenckii. We performed comparative transcriptomic analysis of the brains of sturgeons treated with KISS1-10 during the gonadal sex-differentiation-sensitive period (170-210days post-hatching (dph)) using an Illumina sequencing platform...
September 26, 2016: Gene
Rabab H Sayed, Muhammed A Saad, Ayman E El-Sahar
Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s...
September 27, 2016: Toxicology and Applied Pharmacology
Mayumi Okamoto, Kyosuke Naka, Kiichi Ishiwata, Isao Shimizu, Jun Toyohara
OBJECTIVE: 7α-Substituted androgen derivatives may have the potential to visualize androgen receptors with positron emission tomography. In the present study, we synthesized fluoropropyl derivatives of 7α-(3-[(18)F]fluoropropyl)-testosterone ([(18)F]7) and 7α-(3-[(18)F]fluoropropyl)-dihydrotestosterone ([(18)F]15), and characterized their in vitro binding, in vivo biodistribution, and performed blocking studies in mature androgen deprived male rats. METHODS: We synthesized [(18)F]7 and [(18)F]15...
September 28, 2016: Annals of Nuclear Medicine
Charles E Roselli, Rebecka Amodei, Kyle Gribbin, Keely Corder, Fred Stormshak, Charles T Estill
Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess testosterone exposure. The objective of this study was to determine the effect of exogenous exposure to testosterone on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to 58 of gestation acutely decreased (P<0...
September 27, 2016: Endocrinology
Luca De Toni, Diego Guidolin, Vincenzo De Filippis, Simone Tescari, Giacomo Strapazzon, Maria Santa Rocca, Alberto Ferlin, Mario Plebani, Carlo Foresta
The undercarboxylated form of osteocalcin (ucOC) regulates male fertility and energy metabolism, acting through the G protein-coupled receptor GPRC6A thus forming a new pancreas-bone-testis axis. Recently, GPRC6A has also been suggested to mediate the non-genomic responses of free testosterone (T). However, these data did not consider the physiological scenario, where circulating T is mainly bound to sex hormone-binding globulin (SHBG) and only a small percentage circulates freely in the blood. Here, by the use of computational modelling, we document the existence of similar structural moieties between ucOC and SHBG that are predicted to bind to GPRC6A at docking analysis...
September 27, 2016: Endocrinology
Alexandra I Lazar, Frank Biedermann, Kamila R Mustafina, Khaleel I Assaf, Andreas Hennig, Werner M Nau
Cucurbit[n]urils (CBn, n = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations...
October 5, 2016: Journal of the American Chemical Society
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