Endocrinology, Vol 137, 1714-1718, Copyright © 1996 by Endocrine Society

ARTICLES

Suppression of endogenous corticosterone levels in vivo increases the steroidogenic capacity of purified rat Leydig cells in vitro

HB Gao, LX Shan, C Monder and MP Hardy
Center for Biomedical Research, Population Council, New York, New York 10021, USA.

In vitro studies have shown that corticosterone (B) directly inhibits testosterone (T) production by purified Leydig cells but does so only at high concentrations. 11 beta-Hydroxysteroid dehydrogenase (11 beta- HSD) in Leydig cells oxidatively inactivates B, lowering its effective concentration, thus protecting against the suppressive effect of glucocorticoid on T production. The aim of the present study was to assess the significance of B at physiological levels in modulating T production and 11 beta-HSd activity in Leydig cells. To determine the effects of endogenous B on Leydig cell steroidogenesis, male rats (200- 250 g body wt) were adrenalectomized (ADX), while control rats were subjected to sham surgery (SHAM). Seven days after surgery: T and LH were measured in serum; T production was measured in aliquots of spent culture media from 3-h incubations of purified Leydig cells; 11 beta- HSD activity and messenger RNA was measured in purified Leydig cells. ADX rats had elevated serum T (P < 0.05) in contrast to SHAM control or ADX rats that received B replacement (1 mg/100 g body wt per day, i.p., on the final 3 days). Serum LH levels were uninfluenced by ADX, with or without B replacement (SHAM), 0.45 +/- 0.16 ng/ml; ADX, 0.35 +/- 0.13 ng/ml; ADX + B, 0.61 +/- 0.09 ng/ml, NS, P > 0.05). This indicated that the alteration of T production was induced by a mechanism that is independent of LH. ADX nearly doubled LH-stimulated T production by purified Leydig cells, from 106.3 +/- 9.3 (SHAM) to 183.2 +/- 16.7 (ADX) ng/10(6) cells.3 h (mean +/- SEM for three replications of the experiment, P < or = 0.02). T production by Leydig cells from the ADX + B treatment group was suppressed to 53% of SHAM values, indicating that B inhibits T production after ADX. The oxidative activity of 11 beta- HSD in Leydig cells exceeded its reductive activity, and both activities declined after ADX. The decline in 11 beta-HSD activities after ADX was prevented by B replacement. Similarly, the steady state levels of 11 beta-HSD messenger RNA declined in Leydig cells after ADX, and this decline was prevented by B replacement. We conclude that physiological levels of B exert a tonic, negative control directly on Leydig cell steroidogenesis and also induce intracellular 11 beta-HSD activity, thereby protecting against B-mediated inhibition of T production. By modulating the level of active glucocorticoid in Leydig cells, 11 beta-HSD is thus a significant determinant of their steroidogenic capacity.

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