Corticosterone impairs the mRNA expression and activity of 3β- and 17β-hydroxysteroid dehydrogenases in adult rat Leydig cells

Abstract

Clinical and experimental studies, including our own observations, have shown the adverse effects of excess glucocorticoids on testicular steroid hormone production. The present study was designed to gain insight into the molecular mechanisms by which excess corticosterone impairs Leydig cell steroidogenesis. To achieve this, adult rats were administered with corticosterone-21-acetate (2 mg/100 g body weight) twice daily for 15 days. After the treatment period, rats were killed by decapitation. The testes were removed, decapsulated aseptically and used for the isolation of Leydig cells. Purified Leydig cells were used for assessing the activity of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSDs) and total RNA isolation. For in vitro studies, purified Leydig cells (7.5 x 10(6) cells) of control rats were plated in culture flasks and exposed to different concentrations (50, 100, 200, 400, and 800 nmol/L) of corticosterone for 24 h. At the end of incubation, total RNA was isolated from cultured Leydig cells, and the mRNA of 3beta- and 17beta-HSDs was quantified by RT-PCR. A significant reduction in the activities and levels of 3beta-HSD type-I and 17beta-HSD type-III mRNAs in Leydig cells were observed. In vitro studies demonstrated a dose-dependent significant impairment in both the activity and mRNA expression of these enzymes. These results suggest that corticosterone might have a direct effect on the transcription of the genes of 3beta- and 17beta-HSD. It is inferred from the present in vivo and in vitro studies that one of the molecular mechanisms by which excess corticosterone decreases the steroidogenic potency of Leydig cells is by suppressing the mRNA expression of 3beta-HSD type-I and 17beta-HSD type-III enzymes.

Repeated immobilization stress disturbed steroidogenic machinery and stimulated the expression of cAMP signaling elements and adrenergic receptors in Leydig cells

“…It was suggested that corticosterone might have a direct effect on the transcription of the genes for HSD3B and HSD17B. The in vivo and in vitro studies showed that one of the molecular mechanisms by which excess corticosterone decreases the steroidogenic potency of Leydig cells is by suppressing the mRNA expression of HSD3B1 and HSD17B3 enzymes (6). On the other hand, it was reported that the mRNA, protein, and activity of HSD3B were significantly increased in Leydig cells of corticosterone-deficient animals, whereas the mRNA levels and the specific activities of CYP11A1 and HSD17B were decreased (57).…”

Brain microglia express steroid-converting enzymes in the mouse

“…by [60]). Increased glucocorticoid levels can block steroidogenesis in testicular Leydig cells [61,62], and may have similar effects in brain microglia. We tested whether direct stimulation with corticosterone would decrease steroid-converting enzyme expression, however corticosterone failed to reduce StAR, 17␤HSD1, or 5␣R expression in vitro in both resting and LPS-activated microglia (data not shown).…”

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

“…For example, it is well established that conditions associated with high levels of circulating glucocorticoids, as observed in stress, Cushing syndrome, and long-term therapy with synthetic glucocorticoids, disrupt male fertility (Gabrilove et al, 1974;Sapolsky, 1985;Cooke et al, 2004;Hardy et al, 2005). High plasma levels of glucocorticoids induce reproductive dysfunction by multiple mechanisms, such as suppression of testicular response to gonadotropins (Welsh et al, 1982;Sapolsky, 1985;Orr & Mann, 1992), down-regulation of genes encoding testosterone biosynthetic enzymes (Hales & Payne, 1989;Payne & Sha, 1991;Badrinarayanan et al, 2006), induction of Leydig cell and germ cell apoptosis (Yazawa et al, 2000;Gao et al, 2002Gao et al, , 2003, and induction of oxidative stress in the epididymis (Balasubramanian et al, 1987;Dhanabalan et al, 2010Dhanabalan et al, , 2011Dhanabalan et al, , 2013.…”