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Testosterone synthesis

I Savchuk, M L Morvan, J P Antignac, K Gemzell-Danielsson, B Le Bizec, O Söder, K Svechnikov
It is generally accepted that androgens produced by fetal Leydig cells (FLC) control proper masculinization of the male external genitalia. Here, we hypothesized that the human genital tubercle (GT) has potential to synthesize androgens independently of FLC at early pregnancy. We observed that human GT of both genders have capacity to synthesize steroids of the Δ4 , Δ5 and alternative pathway of DHT synthesis including the androgen itself. The presence of steroids in the GT was associated with the expression of corresponding steroidogenic enzymes...
June 18, 2018: Molecular and Cellular Endocrinology
Sara Della Torre, Nico Mitro, Clara Meda, Federica Lolli, Silvia Pedretti, Matteo Barcella, Luisa Ottobrini, Daniel Metzger, Donatella Caruso, Adriana Maggi
Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice...
June 6, 2018: Cell Metabolism
Mayank Choubey, Ashutosh Ranjan, Puran S Bora, Fátima Baltazar, Amitabh Krishna
Obesity is a major health problem that is linked to decreased sperm count. It is hypothesized that an obesity-associated reduction in adiponectin secretion may be responsible for impairment of spermatogenesis. Therefore, the aim of the study was to evaluate the direct role of adiponectin in spermatogenesis and steroid synthesis in adult mice. This study showed that adiponectin receptors (AdipoR1 and AdipoR2) were localized in Leydig cells and seminiferous tubules in the testis of adult mice. The result of the in vitro study showed the direct action of adiponectin on spermatogenesis by stimulating cell proliferation (PCNA) and survival (Bcl2) and by suppressing cell apoptosis...
June 14, 2018: General and Comparative Endocrinology
Livio Casarini, Daniele Santi, Giulia Brigante, Manuela Simoni
Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in a ∼90 min half-life molecule targeting the gonads, to regulate gametogenesis and androgen synthesis...
June 13, 2018: Endocrine Reviews
Yu V Ukraintseva, K M Liaukovich, А A Polishchuk, О V Martynova, D A Belov, E S Simenel, М Meira E Cruz, А N Nizhnik
OBJECTIVES: Levels of steroid hormones such as androgens and cortisol exhibit circadian variation, and their fluctuations are related to the sleep-wake cycle. Currently, the functional role of different stages of sleep in steroid hormone secretion remains unclear. The present study aims to explore the effect of slow-wave sleep (SWS) suppression on morning levels of cortisol and androgens. METHODS: Twelve healthy male volunteers participated in two experimental sessions: a session with selective SWS suppression during night sleep and a session with regular night sleep (control)...
May 12, 2018: Sleep Medicine
Erkut Ilaslan, Pierre Calvel, Dominika Nowak, Maria Szarras-Czapnik, Jolanta Slowikowska-Hilczer, Anna Spik, Pauline Sararols, Serge Nef, Jadwiga Jaruzelska, Kamila Kusz-Zamelczyk
Identification of novel genes involved in sexual development is crucial for understanding disorders of sex development (DSD). Here, we propose a member of the START domain family, the X chromosome STARD8, as a DSD candidate gene. We have identified a missense mutation of this gene in 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue of one of the sisters contained Leydig cells overloaded with cholesterol droplets, i.e., structures previously identified in 46,XY DSD patients carrying mutations in the STAR gene encoding another START domain family member, which is crucial for steroidogenesis...
June 8, 2018: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
Tiago J Costa, Graziela S Ceravolo, Cinthya Echem, Carolina M Hashimoto, Beatriz P Costa, Rosangela A Santos-Eichler, Maria Aparecida Oliveira, Francesc Jiménez-Altayó, Eliana H Akamine, Ana Paula Dantas, Maria Helena C Carvalho
Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to development of cardiovascular diseases including hypertension and it also increases cytochrome P -450-induced 20-HETE synthesis which in turn results in vascular dysfunction...
2018: Frontiers in Physiology
Song Wang, Peng Xia, Nicholas A Cacalano, Haikun Xu, Dejun Li
Androgen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders of sex development (46,XY DSD). This syndrome is an X-linked recessive genetic disease characterized by resistance to the actions of androgens in an individual with a male karyotype and it is caused by mutations in the androgen receptor (AR) gene. We evaluated two siblings with primary amenorrhea, normal secondary sex characteristics, absence of uterus and ovaries, intra-abdominal testis, and elevated testosterone levels. Sequence analysis of the AR gene revealed a splice acceptor site mutation in intron 2 (c...
May 30, 2018: Steroids
Daniel Hettel, Ao Zhang, Mohammad Alyamani, Michael Berk, Nima Sharifi
3βHSD1 enzymatic activity is essential for synthesis of potent androgens from adrenal precursor steroids in prostate cancer. A germline variant in HSD3B1, the gene that encodes 3βHSD1, encodes for a stable enzyme, regulates adrenal androgen dependence, and is a predictive biomarker of poor clinical outcomes after gonadal testosterone deprivation therapy. However, little is known about HSD3B1 transcriptional regulation. Generally, it is thought that intratumoral androgen synthesis is up-regulated after gonadal testosterone deprivation, enabling development of castration-resistant prostate cancer (CRPC)...
May 29, 2018: Endocrinology
Chau T Tay, Anju E Joham, Danielle S Hiam, Moustafa A Gadalla, Jyotsna Pundir, Shakila Thangaratinam, Helena J Teede, Lisa J Moran
BACKGROUND: Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of non-reproductive outcomes in PCOS is unknown. OBJECTIVE: To summarise and appraise the methodological quality of systematic reviews and meta-analyses evaluating pharmacological and surgical treatments for non-reproductive outcomes in PCOS. METHODS: A literature search from MEDLINE, EMBASE, CINAHL PLUS, and PROSPERO was performed from inception until 15th of September 2017...
May 30, 2018: Clinical Endocrinology
Jigal Haas, Rawad Bassil, Noa Gonen, Jim Meriano, Andrea Jurisicova, Robert F Casper
BACKGROUND: Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation...
May 29, 2018: Reproductive Biology and Endocrinology: RB&E
Senem Ozcan-Sezer, Elif Ince, Atilla Akdemir, Özlem Öztürk Ceylan, Sibel Suzen, Hande Gurer-Orhan
1. A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer. 2. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use...
May 28, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Michal Jurášek, Markéta Černohorská, Jiří Řehulka, Vojtěch Spiwok, Tetyana Sulimenko, Eduarda Dráberová, Maria Darmostuk, Soňa Gurská, Ivo Frydrych, Renata Buriánová, Tomáš Ruml, Marián Hajdúch, Petr Bartůněk, Pavel Dráber, Petr Džubák, Pavel B Drašar, David Sedlák
Microtubule dynamics is one of the major targets for new chemotherapeutic agents. This communication presents the synthesis and biological profiling of steroidal dimers based on estradiol, testosterone and pregnenolone bridged by 2,6-bis(azidomethyl)pyridine between D rings. The biological profiling revealed unique properties of the estradiol dimer including cytotoxic activities on a panel of 11 human cell lines, ability to arrest in the G2/M phase of the cell cycle accompanied with the attenuation of DNA/RNA synthesis...
May 24, 2018: Journal of Steroid Biochemistry and Molecular Biology
Emma H Allott, Elizabeth M Masko, Alexis R Freedland, Everardo Macias, Kristine Pelton, Keith R Solomon, Elahe A Mostaghel, George V Thomas, Salvatore V Pizzo, Michael R Freeman, Stephen J Freedland
BACKGROUND: Some, but not all, epidemiologic evidence supports a role for cholesterol, the precursor for steroid hormone synthesis, in prostate cancer. Using a PTEN-null transgenic mouse model of prostate cancer, we tested the effect of modifying serum cholesterol levels on prostate tumor development and growth. We hypothesized that serum cholesterol reduction would lower tumor androgens and slow prostate cancer growth. METHODS: PTENloxP/loxP -Cre+ mice consuming ad libitum high fat, high cholesterol diets (40% fat, 1...
May 23, 2018: Prostate Cancer and Prostatic Diseases
Ya-Li Yang, Li-Feng Sun, Yan Yu, Tian-Xia Xiao, Bao-Bei Wang, Pei-Gen Ren, Hui-Ru Tang, Jian V Zhang
BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. METHODS: Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days...
May 24, 2018: Reproductive Biology and Endocrinology: RB&E
Juan Díaz-Ramos, Maribel Flores-Flores, María E Ayala, Andrés Aragón-Martínez
Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p-chloroamphetamine (PCA) (0...
May 22, 2018: Systems Biology in Reproductive Medicine
Jie Hou, Yujing Su, Wang Lin, Honghui Guo, Li Li, Donald M Anderson, Dapeng Li, Rong Tang, Wei Chi, Xi Zhang
Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes...
May 14, 2018: Environmental Pollution
Muafia Jabeen, Muhammad Iqbal Choudhry, Ghulam Abbas Miana, Khondaker Miraz Rahman, Umer Rashid, Hidayat-Ullah Khan, Arshia, Abdul Sadiq
Steroidal hormones progesterone and testosterone play a vital role in breast and prostate cancers. In this research, we have synthesized and characterized a total of thirty-one (31) new nitrogenous derivatives of progesterone and testosterone. The synthesized derivatives (1-31) were screened for their anti-cancer potential against MCF-7 and PC-3 cell lines of breast using MTT assay. The compounds 1-31exhibited significant inhibitory potentials against MCF-7 and PC-3 cell lines. In MCF-7 assay, compound 17 displayed IC50 value of 04 ±0...
May 14, 2018: Steroids
Xianglong Zhao, Wangjie Xu, Jiajie Wu, Dong Zhang, Abdelrahman Abou-Shakra, Ling Di, Zhaoxia Wang, Lianyun Wang, Fan Yang, Zhongdong Qiao
A new report has shown that nicotine exposure can decrease serum testosterone by apoptosis in Leydig cells; however, in our previous studies, we have almost never observed apoptosis there. The purpose of this study is to ensure whether apoptosis or autophagy in Leydig cells occurred. Our results confirmed again that the concentration of testosterone in the sera of nicotine-treated mice statistically decreased (P < 0.05). Furthermore, the data of single cell transcriptome indicated that the expression of autophagy-related genes was increased after nicotine exposure...
May 10, 2018: International Journal of Biochemistry & Cell Biology
Chihiro Miyashita, Atsuko Araki, Takahiko Mitsui, Sachiko Itoh, Houman Goudarzi, Seiko Sasaki, Jumboku Kajiwara, Tsuguhide Hori, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi
BACKGROUND: Prenatal exposure to dioxin-like compounds (DLCs) irreversibly affects fetal reproductive and steroid hormone synthesis. OBJECTIVE: This study aimed to assess the relationships between maternal DLCs and cord blood reproductive and steroid hormones. METHODS: Participants in this study were pregnant women who enrolled in the Sapporo Cohort of the Hokkaido Study between 2002 and 2005. We quantified 29 DLCs during the 2nd and 3rd trimesters in maternal blood...
May 9, 2018: Environment International
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