Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation.
The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.
Orpana
A K
AK
Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Finland.
Orava
M M
MM
Vihko
R K
RK
Härkönen
M
M
Eriksson
C J
CJ
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D000077604:Fomepizole; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013256:Steroids / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D006063:Chorionic Gonadotropin; D011720:Pyrazoles; D013256:Steroids; D000431:Ethanol; D013739:Testosterone; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D003345:Corticosterone