Region-specific regulation of cytochrome P450 aromatase messenger ribonucleic acid by androgen in brains of male rhesus monkeys.
We demonstrated previously that testosterone regulates aromatase activity in the anterior/dorsolateral hypothalamus of male rhesus macaques. To determine the level of the androgen effect, we developed a ribonuclease protection assay to study the effects of testosterone or dihydrotestosterone (DHT) on aromatase (P450(AROM)) mRNA in selected brain areas. Adult male rhesus monkeys were treated with testosterone or DHT. Steroids in serum were quantified by RIA. Fourteen brain regions were analyzed for P450(AROM) mRNA. Significant elevations of its message over controls (P<0.05) were found in the medial preoptic area/anterior hypothalamus of both androgen treatment groups and the medial basal hypothalamus of the testosterone-treated males. Other brain areas were not affected by androgen treatment. We conclude that testosterone and DHT regulate P450(AROM) mRNA in brain regions that mediate reproductive behaviors and gonadotropin release. The P450(AROM) mRNA of other brain areas is not androgen dependent. Brain-derived estrogens may also be important for maintaining neural circuitry in brain areas not related to reproduction. The control of P450(AROM) mRNA in these areas may differ from what we report here, but it is equally important to understand the function of in situ estrogen formation in these areas.
Resko
J A
JA
Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. reskoj@ohsu.edu
Pereyra-Martinez
A C
AC
Stadelman
H L
HL
Roselli
C E
CE
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007032:Hypothalamus, Anterior / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D011301:Preoptic Area / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D000728:Androgens; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase