Nongenomic effect of testosterone on chloride secretion in cultured rat efferent duct epithelia

Abstract

Short-circuit current (I(sc)) technique was used to investigate the role of testosterone in the regulation of chloride secretion in cultured rat efferent duct epithelia. Among the steroids tested, only testosterone, and to a lesser extent, 5alpha-dihydrotestosterone (5alpha-DHT), reduced the basal and forskolin-induced I(sc) in cultured rat efferent duct epithelia when added to the apical bathing solution. Indomethacin, a 3alpha-hydroxysteroid dehydrogenase, did not affect the inhibitory effect of 5alpha-DHT. The effect of testosterone occurred within 10-20 s upon application and was dose dependent with apparent IC(50) value of 1 microM. The effect was abolished by removal of Cl(-) but not HCO from the normal Krebs-Henseleit solution, suggesting that testosterone mainly inhibited Cl(-) secretion. The efferent duct was found to be most sensitive to testosterone, while the caput and the cauda epididymidis were only mildly sensitive. Cyproterone acetate, a steroidal antiandrogen, or flutamide, a nonsteroidal antiandrogen, did not block the effect of testosterone on the forskolin-induced I(sc), nor did protein synthesis inhibitors, cycloheximide, or actinomycin D. However, pertussis toxin, a G(i) protein inhibitor, attenuated the inhibition of forskolin-induced I(sc) by testosterone. Testosterone caused a dose-dependent inhibition of forskolin-induced rise in cAMP in efferent duct cells. It is suggested that the rapid effect of testosterone was mediated through a membrane receptor that is negatively coupled to adenylate cyclase via G(i) protein. The role of nongenomic action of testosterone in the regulation of electrolyte and fluid transport in the efferent duct is discussed.

Androgens Inhibit Estradiol-17β Synthesis in Atlantic Croaker (Micropogonias undulatus) Ovaries by a Nongenomic Mechanism Initiated at the Cell Surface1

“…However, the results of the current study show that the antiandrogens cyproterone acetate and p,pЈ-DDE do not affect the androgenic inhibition of in vitro gonadotropin-stimulated estradiol production despite the previous identification of a nuclear androgen receptor (AR2) in the croaker ovary [18]. These results, along with other studies showing that antiandrogens do not inhibit rapid, nongenomic androgen actions [16,[37][38][39][40], further support the existence of nonclassical androgen receptors. However, it should be noted that although cyproterone acetate and p,pЈ-DDE are weak competitors for AR2 [19], the ability of these synthetic compounds to act as antiandrogens has not been established in croaker.…”

Finasteride for Chronic Central Serous Chorioretinopathy

“…The enzyme inhibited by finasteride, 5α– reductase, is expressed in human RPE cells27. Analogous to the effect of glucocorticoids on RPE cells, DHT inhibits the electric potential in epididymal epithelium28. The effects of DHT on the RPE pump (if any) are not known, but if DHT is indeed produced by 5α– reductase in RPE cells and has a deleterious effect on the RPE pump, then its inhibition may help improve subretinal fluid resorption by RPE cells.…”

Steroids Modulate Transepithelial Resistance and Na+ Absorption Across Cultured Porcine Vas Deferens Epithelia1

“…Testosterone has been shown to stimulate fluid and anion secretion by a canine kidney cell line, MDCK cells [33]. Most importantly, it has been shown that testosterone and dihydrotestosterone, but not estrogen, dexamethasone, or aldosterone, reduce Cl Ϫ -dependent, forskolin-stimulated ion transport across cultured rat efferent ductile epithelium [34]. Although these effects of steroid hormones on ion transport are intriguing, it must be noted that their rapid time course, the requirement for high concentrations, and a pharmacological profile that is inconsistent with known estrogen or androgen receptors argue strongly that these effects are unrelated to the receptor-mediated events for which we were testing in the present experiments.…”