Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the developing male rat.
The ontogeny of the effects of alcohol on serum testosterone levels was examined in male rats throughout sexual maturation (25-70 days). Alcohol decreased serum testosterone levels in rats 45 days or older as expected. In contrast to these results, we found precisely the opposite effects in prepubescent male rats (25-30 days old): namely, a marked stimulation of serum testosterone. Alcohol produced dose-dependent increases in serum testosterone levels in the prepubescent animal with increases of over 300% observed. In contrast to the biphasic effects of alcohol on serum testosterone levels in the developing animal, we found either no changes or modest decreases in serum luteinizing hormone levels at all ages tested. These data indicate that the increase in testosterone occurred independently of changes in luteinizing hormone in the prepubescent animal. Thus, it appears that the primary site of action of alcohol on the hypothalamic-pituitary-gonadal axis in prepubescent male rats is the testes and that alcohol acts to directly stimulate testosterone's biosynthesis. In contrast, alcohol appears to act at both central and testicular sites in rats 45 days or older to depress the synthesis and release of testosterone. The mechanisms underlying these age-dependent, biphasic effects of alcohol on serum testosterone levels are unknown at the present time, but it seems unlikely that differences in the biodisposition of alcohol were involved.(ABSTRACT TRUNCATED AT 250 WORDS)
Little
P J
PJ
Washington University School of Medicine, Department of Psychiatry, St. Louis, Missouri.
Adams
M L
ML
Cicero
T J
TJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*
D000431:Ethanol; D013739:Testosterone; D007986:Luteinizing Hormone