The functional importance of sex steroid hormones (testosterone and estrogens), derived from extragonadal tissues, has recently gained significant appreciation. Circulating dehydroepiandrosterone (DHEA) is peripherally taken up and converted to testosterone by 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD, and testosterone in turn is irreversibly converted to estrogens by aromatase cytochrome P-450 (P450arom). Although sex steroid hormones have been implicated in skeletal muscle regulation and adaptation, it is unclear whether skeletal muscles have a local steroidogenic enzymatic machinery capable of metabolizing circulating DHEA. Thus, here, we investigate whether the three key steroidogenic enzymes (3beta-HSD, 17beta-HSD, and P450arom) are present in the skeletal muscle and are capable of generating sex steroid hormones. Consistent with our hypothesis, the present study demonstrates mRNA and protein expression of these enzymes in the skeletal muscle cells of rats both in vivo and in culture (in vitro). Importantly, we also show an intracellular formation of testosterone and estradiol from DHEA or testosterone in cultured muscle cells in a dose-dependent manner. These findings are novel and important in that they provide the first evidence showing that skeletal muscles are capable of locally synthesizing sex steroid hormones from circulating DHEA or testosterone.

The cellular distribution of two oestrogen receptor (ER) subtypes, ER and ER mRNAs, was studied in the entire female reproductive organ of the rat using in situ hybridization. Expression of ER and ER mRNAs was predominant in the reproductive tract and ovary respectively. ER mRNA had the most pronounced expression in epithelial cells and subepithelial stromal cells from the oviduct to the vagina, while in the ovary it was moderately detected in only the theca folliculi and interstitial glands. The oviduct showed a region-dependent expression of ER mRNA: the isthmus had the most intense signals while the infundibulum revealed a low intensity of expression. Signals for ER mRNA in the ovary were most intense in the granulosa cells of healthy follicles, whereas degenerating follicles lacked any significant expression. Less intense signals for ER mRNA were localized in the theca folliculi and corpus luteum. Detectable levels of ER mRNA were observed in the subepithelial stromal cells from the oviduct to the vagina. This study shows that the two ER subtypes are differentially expressed in cells and compartments of the reproductive organ, suggesting that the mediation of oestrogen action in these tissues may be accomplished through the respective predominant receptor.

Body tissues are traditionally classified as estrogen targets based on both the response to the hormone and the presence of estrogen receptors (ERs). We undertook the study on expression of ERalpha and ERbeta in the penis to identify compartments/cells responsive to estrogen, using immunohistochemistry, Western blotting, in situ hybridization, and RT-PCR analyses. Expressions of ERalpha and ERbeta in the rat penis were age dependent at both mRNA and protein levels, with the most intense signals being observed during the perinatal period and declining thereafter with age. Initial signals (fetal d 17) of ERalpha were localized to the mesenchyme and subepithelial stroma and later (postnatal d 2) to the corpus spongiosus, corpus cavernosus, and urethral epithelia. ERbeta was initially detected by postnatal d 2 and was localized diffusely in corpus spongiosus and cavernosus in immature rats. In the adult, both ERs were concentrated largely to the urethral epithelia and vascular and neuronal structures. The present study provides the first evidence for ER expression in the penis. Thus, our data add the penis to the list of estrogen-responsive tissues in males and provide a base and insight for future studies aimed at investigating a functional role of estrogen in the penis, especially in development.

No abstract