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The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period. It has been assumed that the undifferentiated brain is masculinized by direct induction of transcription by ligand-activated nuclear steroid receptors. We found that a primary effect of gonadal steroids in the highly sexually dimorphic preoptic area (POA) is to reduce activity of DNA methyltransferase (Dnmt) enzymes, thereby decreasing DNA methylation and releasing masculinizing genes from epigenetic repression. Pharmacological inhibition of Dnmts mimicked gonadal steroids, resulting in masculinized neuronal markers and male sexual behavior in female rats. Conditional knockout of the de novo Dnmt isoform, Dnmt3a, also masculinized sexual behavior in female mice. RNA sequencing revealed gene and isoform variants modulated by methylation that may underlie the divergent reproductive behaviors of males versus females. Our data show that brain feminization is maintained by the active suppression of masculinization via DNA methylation. testosterone.

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The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17?-estradiol, progesterone, 17?-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-?-actin smooth muscle and antibodies to each hormone receptor). ER?, ER?, tPR, and AR were detected in females or males. ER? was upregulated by E2 and T and downregulated by P4 in females; in males, ER? was downregulated by P4, E + P, and T. ER? was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats. testosterone.

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Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation. testosterone.

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Buthionine sulfoximine (BSO) inhibits synthesis of glutathione as the main intracellular antioxidant. The aim of the present study is to investigate the effect of BSO-induced oxidative stress on histological structure of testis, testosterone secretion and semen parameters. testosterone.

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Effects of chemical mixtures at environmentally relevant concentrations on endocrine systems of aquatic organisms are of concern. Triclocarban (TCC) and inorganic mercury (Hg(2+)) are ubiquitous in aquatic environments, and are known to interfere with endocrine pathways via different mechanisms of toxic action. However, effects of mixtures of the two pollutants on aquatic organisms and associated molecular mechanisms were unknown. This study examined effects of binary mixtures of TCC and Hg(2+) on histopathological and biochemical alteration of reproductive organs in zebrafish (Danio rerio) after 21 d exposure. The results showed that: 1) At concentrations studied, TCC alone caused little effect on hepatic tissues, but it aggravated lesions in liver caused by Hg(2+) via indirect mechanisms of disturbing homeostasis and altering concentrations of hormones; 2) Histological lesions were more severe in gonads of individuals, especially males, exposed to the binary mixture. Exposure to TCC alone (2.5 or 5?g/L) (measured concentration 140 or 310ng/L) or Hg(2+) alone (5?g/L or 10?g/L (measured concentration 367 or 557ng/L) slightly retarded development of oocytes, whereas co-exposure to nominal concentrations of 5?g/L TCC and 10?g /L Hg(2+) promoted maturation of oocytes. In males, maturation of sperm was slightly delayed by exposure to either TCC or Hg(2+), while their combinations caused testes to be smaller and sperm to be fewer compared with fish exposed to either of the contaminants individually; 3) Lesions observed in fish exposed to binary mixtures might be due to altered transcription of genes involved in steroidogenesis, such as cyp19a, 3beta-HSD, cyp17, 17beta-HSD and modulated concentrations of testosterone and estradiol in blood plasma. The observed results further support the complexity of toxic responses of fish exposed to lesser concentrations of binary chemical mixtures. Since it is impossible to collect empirical information in controlled studies of all possible combinations of toxicants, the application of omics methods might improve the predictive capabilities of results of single classes of chemicals. testosterone.

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The present study demonstrated that estradiol and testosterone have a synergistic effect on early stage atherosclerosis, and replacement therapy with the defined appropriate E2/T ratio can significantly suppress the development of atherosclerosis through reducing the lipid lesions, reducing the formation of foam cells, reducing endothelial injury, modulating the coagulation system function and inhibiting inflammation. testosterone.

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