5 alpha-reductase activity regulates testosterone accumulation in two bands of immature cultured Leydig cells isolated on Percoll density gradients.
The 5 alpha-reductase inhibitor, 4-methyl-4-aza-3-oxo-5 alpha-pregnan-20(s)-carboxylate was utilized to examine maturational changes in testosterone synthesizing capacity of Leydig cells localizing in Band 2 and Band 3 of Percoll density gradients. Immature Band 2 Leydig cells (from 25- to 39-day-old rats) cultured without the 5 alpha-reductase inhibitor, produced increased testosterone in response to hCG or 8-br-cAMP; however, basal, hCG- or 8-br-cAMP-stimulated testosterone accumulation was 4- to 12-fold higher when cells were cultured in the presence of inhibitor. Band 2 cells from older rats produced much less testosterone in response to hCG or 8-br-cAMP (less than 3.5 pmol/10(5], even when cultured with the inhibitor. Although immature Band 3 cells cultured in the absence of 5 alpha-reductase inhibitor produced increased testosterone in response to hCG or 8-br-cAMP, testosterone levels were relatively low, because elevated 5 alpha-reductase prevented appreciable androgen accumulation; however, Band 3 cells from older rats (over 39 days old) accumulated progressively more testosterone, because of the age-dependent decline in 5 alpha-reductase activity. Immature Band 3 cells cultured with the 5 alpha-reductase inhibitor accumulated 20- to 44-fold more testosterone in response to hCG of 8-br-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Murono
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EP
Medical Research Service, WJB Dorn Veterans' Hospital, Columbia, SC.
Washburn
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AL
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D011278:Pregnanes; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D006063:Chorionic Gonadotropin; D011278:Pregnanes; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; C037399:4-methyl-4-aza-3-oxopregnane-20-carboxylate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase