Testosterone regulates aromatase activity in discrete brain areas of male rhesus macaques.
The nonhuman primate brain contains two divergent pathways for testosterone (T) metabolism. Estradiol is biosynthesized from T by aromatization through the first pathway, whereas dihydrotestosterone is produced by the action of 5 alpha-reductase through the second pathway. Previously, we mapped the distribution of these enzyme activities within specific microdissected brain area and determined that aromatase activity (AA), but not 5 alpha-reductase activity (5 alpha RA), was reduced in certain brain areas after castration. In the present study, we measured AA and 5 alpha RA in thirteen brain nuclei and subregions from five castrated and five T-treated castrated male rhesus monkeys to determine whether exogenous androgen treatment could reverse the effects of castration on brain AA. We found that T, administered in a dose that maintained serum levels at 14.2 +/- 1.6 (SEM) ng/ml, suppressed circulating luteinizing hormone (Castrates = 491.9 +/- 86 ng/ml vs. T-treated castrates = 1.8 +/- 0.2 ng/ml), and stimulated AA in specific nuclei including the suprachiasmatic nucleus (n.), periventricular area, ventromedial n., and lateral hypothalamus. T treatment had no significant effect on AA in nine other nuclei or on 5 alpha RA in any brain areas that we studied. These data indicate that AA in diencephalic and limbic structures of the nonhuman primate brain is distributed heterogeneously into androgen-dependent and androgen-independent regions. This distribution is similar to that found in rodents. 5 alpha RA, on the other hand, is more homogeneously distributed than AA in these same brain regions and is not controlled by androgens.
Department of Physiology, Oregon Health Sciences University, Portland 97201.
C E
CE
Roselli
J A
JA
Resko
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D013196:Dihydrotestosterone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D009919:Orchiectomy; D013739:Testosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D013196:Dihydrotestosterone; D013739:Testosterone; D007986:Luteinizing Hormone; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase