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

Abstract

Epithelial cells were isolated from adult porcine vas deferens and grown in the absence or presence of steroid hormones. Transepithelial resistance (R(te)), basal short circuit current (I(sc)), and the effects of selected ion transport modulators on these parameters were evaluated in modified Ussing chambers at three time points (5-8, 11-14, and 18-22 days postseeding). At the earliest time point, no significant differences were observed. At the middle time point, when compared with R(te) in untreated control monolayers, R(te) in monolayers exposed to 17beta-estradiol, aldosterone, cortisol, cortisone, prednisolone, prednisone, and dexamethasone was significantly lower; in contrast, R(te) in monolayers exposed to testosterone, dihydrotestosterone, or progesterone did not differ from that in control monolayers. Treatments with cortisol, prednisolone, and dexamethasone were associated with an elevated basal I(sc) that was amiloride sensitive, indicating ongoing Na(+) absorption by these monolayers. R(te) was increased by amiloride treatment in glucocorticoid-treated monolayers but remained significantly less than that of control monolayers. At the third time point, the postamiloride R(te) of glucocorticoid-treated monolayers was not different from that of control monolayers. Responses to ATP, forskolin, bumetanide, and DASU-02 were not affected by steroid treatment at any time point. Taken together, these results suggest that estrogens and corticosteroids can modulate epithelial function in the distal excurrent duct of the adult male reproductive system. At physiological or pharmacological concentrations, these hormones would be expected to modify the luminal environment (both the ionic composition and pH) to which sperm are exposed and thus affect male fertility.

11β-Hydroxysteroid dehydrogenase enzymes in the testis and male reproductive tract of the boar (Sus scrofa domestica) indicate local roles for glucocorticoids in male reproductive physiology

“…Hence, we would speculate that in this duct, the high NADP(H)-dependent 11bHSD activities, which we observed in this region, may be important in modulating the potential effects of GCs on ion and fluid transport. In light of the presence of sodium-proton co-transporters, any steroidal control of sodium flux within the caput epididymidis would be expected to alter the luminal pH and hence affect the final maturation of sperm in this duct (Pushkin et al 2000, Phillips & Schultz 2002. Previous studies have also reported a predominant 11KSR activity in the rat cauda epididymidis (Waddell et al 2003).…”

Impact of adrenalectomy and dexamethasone treatment on testicular morphology and sperm parameters in rats: insights into the adrenal control of male reproduction

“…Previous studies indicated that normal systemic levels of glucocorticoids may be required for post-natal development of the testis (Weber et al, 2000), fluid transport across the epithelium of the excurrent duct system (Au et al, 1978;Turner & Cesarini, 1983;Phillips & Schultz, 2002) and control of ejaculation and erectile function (Penson et al, 1997;Corona et al, 2012). Experimental conditions in which bilateral adrenalectomy was employed to manipulate the circulating levels of adrenal steroids further indicate an involvement of glucocorticoids in the modulation of spermatogenesis and testicular steroidogenesis (Lescoat et al, 1982;Saxena & Paul, 1987, 1988Gao et al, 1997;Weber et al, 2000), as well as in the fluid reabsorption by epithelial cells from the epididymis and vas deferens (Au et al, 1978;Turner & Cesarini, 1983;Phillips & Schultz, 2002).…”

“…Previous studies indicated that normal systemic levels of glucocorticoids may be required for post-natal development of the testis (Weber et al, 2000), fluid transport across the epithelium of the excurrent duct system (Au et al, 1978;Turner & Cesarini, 1983;Phillips & Schultz, 2002) and control of ejaculation and erectile function (Penson et al, 1997;Corona et al, 2012). Experimental conditions in which bilateral adrenalectomy was employed to manipulate the circulating levels of adrenal steroids further indicate an involvement of glucocorticoids in the modulation of spermatogenesis and testicular steroidogenesis (Lescoat et al, 1982;Saxena & Paul, 1987, 1988Gao et al, 1997;Weber et al, 2000), as well as in the fluid reabsorption by epithelial cells from the epididymis and vas deferens (Au et al, 1978;Turner & Cesarini, 1983;Phillips & Schultz, 2002). In agreement with these observations, the differential expression of the glucocorticoid receptor (GR) and 11b-hydroxysteroid dehydrogenase isoforms in tissues from the male reproductive tract of different species (Schultz et al, 1993;Mohler et al, 1996;Weber et al, 2000;Biagini & Pich, 2002;Waddell et al, 2003;Sharp et al, 2007;Silva et al, 2010;Gladstones et al, 2012;Cabrera-Sharp et al, 2013) indicate that they are targets for glucocorticoid actions.…”

Innate Immunity in the Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens

“…The FBS-induced reduction in TER was circumvented by pretreatment of the cells with the estrogen receptor antagonist, ICI 182,780, indicating that epithelial monolayer integrity is directly influenced by E 2 via its receptor. Estradiol has also been shown to disrupt adheren junctions in endothelial cells [27] and to decrease TER in porcine vas deferens epithelia [28].…”