Comparative aspects of 11 beta-hydroxysteroid dehydrogenase. Testicular 11 beta-hydroxysteroid dehydrogenase: development of a model for the mediation of Leydig cell function by corticosteroids.
It has been shown that stress or disease-induced increases in plasma corticosterone result in diminished testosterone secretion from the testes. This article reviews investigations from our laboratories that explore the role of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in this process. It is proposed that the level of 11 beta-OHSD in Leydig cells dictates the level of intracellular glucocorticoid available to the glucocorticoid receptor and thus the potency of corticosteroid as an inhibitor of testosterone secretion. Stressed and unstressed rats were housed under simulated natural conditions in a Visible Burrow System. Stressed animals showed elevated plasma corticosteroid, lowered plasma testosterone, and diminished testicular 11 beta-OHSD, Immunocytochemical analysis showed that only Leydig cells of the rat testis contain 11 beta-OHSD and glucocorticoid receptors. Half-maximal inhibition of testosterone by Leydig cells required 1.5 nM dexamethasone or 0.4 microM corticosterone. Glycyrrhetinic acid, an inhibitor of 11 beta-OHSD, increased the potency of corticosterone, but did not affect dexamethasone based inhibition. The glucocorticoid receptor blocker, RU 486, prevented inhibition by both corticosterone and dexamethasone. Other classes of steroid were not inhibitors of testosterone biosynthesis. Thus, 11 beta-OHSD oxidizes corticosterone to the inactive metabolite 11-dehydrocorticosterone, relieving steroid-dependent inhibition of Leydig cell function. Lowered enzyme activity increases glucocorticoid dependent inhibition of testosterone production. We conclude that the evidence supports a role of 11 beta-OHSD in testosterone secretion by the testes.
Monder
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Population Council, New York, NY 10021.
Hardy
M P
MP
Blanchard
R J
RJ
Blanchard
D C
DC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007985:Leydig Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013737:Testis / Q000201:enzymology*; D013739:Testosterone / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D013739:Testosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases