11 beta-hydroxysteroid dehydrogenase is a predominant reductase in intact rat Leydig cells

C M Leckie, L A M Welberg, J R Seckl

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11 beta-Hydroxysteroid dehydrogenases (11 beta-HSDs) interconvert active corticosterone and inert 11-dehydrocorticosterone. In tissue homogenates, 11 beta-HSD type 1 (11 beta-HSD-1) exhibits bath 11 beta-dehydrogenase (corticosterone inactivating) and 11 beta-reductase (corticosterone regenerating) activities, whereas 11 beta-HSD type 2 (11 beta-HSD-2) is an exclusive dehydrogenase. In the rat testis, 11 beta-HSD has been proposed to reduce glucocorticoid inhibition of testosterone production, promoting puberty and fertility.. This hypothesis presupposes dehydrogenation predominates. 11 beta-HSD-1 immunoreactivity has been localised to Leydig cells. However, recent studies suggest that 11 beta-HSD-1 is predominantly an 11 beta-reductase in many intact cells. We therefore examined the expression and reaction direction of 11 beta-HSD isozymes in cultures of intact rat Leydig cells. Reverse transcriptase PCR demonstrated expression of 11 beta-HSD-1, but not 11 beta-HSD-2 mRNA in rat testis. Primary cultures of intact rat Leydig cells showed predominant 11 beta-reductase activity, activating 50-70% of 11-dehydrocorticosterone to corticosterone over 3h, whereas 11 beta-dehydrogenation was <5%. Although both dexamethasone (10 nM) and corticosterone (1 mu M) modestly inhibited LH-stimulated testosterone production by Leydig cells, inert 11-dehydrocorticoscerone (1 mu M) had similar effects, suggesting 11 beta-reductase is functionally important. Carbenoxolone (10(-5) M) inhibited Ilpreduction in intact Leydig cells. However, although carbenoxolone reduced Leydig cell testosterone production, this also occurred in the absence of glucocorticoids, suggesting effects distinct from modulation of corticosteroid access to Leydig cells. In conclusion, rat Leydig cell 11 beta-HSD-1 is unlikely to reduce glucocorticoid access to testicular receptors. More likely, 11 beta-reductase amplifies glucocorticoid action, perhaps to maintain Leydig cell metabolic and endocrine functions.

Original languageEnglish
Pages (from-to)233-238
Number of pages6
JournalJournal of Endocrinology
Issue number2
Publication statusPublished - Nov 1998


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