Neonatal programming of ethylmorphine demethylase and corticosteroid 5 alpha-reductase by testosterone, dihydrotestosterone, and estradiol. Effects of an anti-estrogen, an anti-androgen, and an inhibitor of estrogen synthetase.
The neonatal imprinting of ethylmorphine demethylase and corticosteroid 5 alpha-reductase was studied. Males, castrated at birth (day 1), were injected (sc) with testosterone, dihydrotestosterone, or estradiol on days 2, 4, and 6 and with testosterone (2 mg/rat/day) on days 50-59. Microsomes were prepared on day 60. All three steroids, at greater than or equal to 0.73 mumol/pup, increased the apparent Vmax and decreased the apparent Km of the demethylase to values that did not differ (p less than 0.05) from those of intact adult males. Analogously, all steroids, at greater than or equal to 0.73 mumol/pup, decreased the apparent Vmax of the reductase to intact male values; its apparent Km was increased to adult male values by both androgens (at greater than or equal to 0.37 mumol/pup) and by estradiol (at greater than or equal to 0.73 mumol/pup). Flutamide (1.45 mumol/pup) failed to alter these effects indicating that androgen receptors are not involved in the imprinting process. Nafoxidine (1.45 mumol/pup) blocked the effects of all three steroids, indicating that androgens and estrogens both imprint via the estrogen receptor. An inhibitor of androgen aromatase, 1,4,6-androstatriene-3, 17 dione, blocked the imprinting effects of testosterone, but not those of dihydrotestosterone. Thus, testosterone is oxidized to estradiol prior to imprinting, while dihydrotestosterone imprints as the parent compound. The latter may reflect a pharmacologic occupancy of the estrogen receptor by dihydrotestosterone.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002369:Castration; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology*
D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase