Aromatase activity in developing guinea pig brain: ontogeny and effects of exogenous androgens.
The formation of estrogens from androgens by aromatase in the developing brain is an important step in the sexual differentiation of many species. We characterized aromatase activity (AA) in a high-speed pellet of brain tissue from fetal guinea pigs. The apparent substrate affinity (approximately 17 nM) was comparable to reported values in other species. Aromatase activity was highest in the amygdala (AMG) and preoptic area (POA), with lesser amounts in the septum (SEPT) and medial basal hypothalamus (MBH). Activity was low but measurable in parietal cortex (CTX). In the AMG, POA, SEPT, and MBH, AA was highest in early gestation (Days 35-40) and showed a steady decline through development. No sex difference in AA was apparent. We also determined the effects of administration of exogenous androgens to pregnant females on brain AA in the fetus. Testosterone propionate (5 mg/day on Days 30-39 followed by 1 mg/day on Days 40-50) caused a significant increase (p < 0.05) in AA found in the MBH and CTX. Administration of dihydrotestosterone propionate (2.5 mg/day on Days 30-39 followed by 1 mg/day on Days 40-50) significantly stimulated AA in SEPT, MBH, and CTX. These data demonstrate that the fetal guinea pig brain contains high levels of AA during the critical period of sexual differentiation. Treatment with high levels of exogenous androgens consistently induces AA in the MBH and CTX. These latter effects may be among the mechanisms through which exogenous androgens act on the developing brain.
Connolly
P B
PB
Department of Physiology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Roselli
C E
CE
Resko
J A
JA
D000679:Amygdala / Q000196:embryology / Q000201:enzymology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D005260:Female; D005865:Gestational Age; D006168:Guinea Pigs; D007033:Hypothalamus, Middle / Q000196:embryology / Q000201:enzymology; D008297:Male; D010296:Parietal Lobe / Q000196:embryology / Q000201:enzymology; D011247:Pregnancy; D011301:Preoptic Area / Q000196:embryology / Q000201:enzymology; D012733:Sex Differentiation; D013379:Substrate Specificity; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D013739:Testosterone; D001141:Aromatase