Androgen metabolism in target tissues constitutes an important step for understanding hormone action. The in situ aromatization of androgen represents one of these metabolic events. We characterized aromatase activity (AA) in a microsomal preparation of brain tissue from adult guinea pigs since earlier reports questioned its presence in neural tissues of this species. Analyses revealed an apparent substrate affinity (approximately 17 nM) that was equivalent in adult males and females. However, adult male brains contained greater quantities of AA than female brains. Specifically, AA in the preoptic area (POA: p less than 0.05) and the medial basal hypothalamus (MBH; p less than 0.01) was greater in males than in females. AA was concentrated in the limbic system and hypothalamus (amygdala greater than POA greater than septum greater than MBH), whereas low levels were consistently measured in cortical tissue. In vitro estrogen formation was significantly lower in POA (p less than 0.05) and MBH (p less than 0.01) after castration. After dihydrotestosterone treatment, AA returned to levels equal to or greater than those observed in intact males. These data indicate that AA does exist in the guinea pig brain and is modulated by androgens through the androgen receptor. The presence of high levels of aromatase activity may suggest a role for locally formed estrogens in brain function in this species.

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In this study we compared the binding characteristics of methyltrienolone (R1881) in pooled cytosols from the hypothalamus-preoptic area-amygdala-septum (HPAS) of adult and fetal rhesus macaques. In addition, we studied the ontogeny of cytosolic androgen receptors (AR) in fetal neural tissue. Intact adult males and fetal rhesus monkeys of known gestational age were our experimental subjects. Fetuses were delivered by cesarean section at 50, 65, 80, and 150 days gestation. HPAS cytosols from 150-day fetuses and adult males were incubated with the synthetic ligand, [3H]R1881, for determining AR characteristics and to validate the assay. A single high affinity, low capacity receptor for R1881 was found in HPAS cytosols. The apparent dissociation constant was similar between adult and fetal HPAS (1.09 X 10(-10) vs. 1.59 X 10(-10) M, respectively). Binding specificity was determined by the addition of excess radioinert testosterone (T), 5 alpha-dihydrotestosterone, estradiol, or progesterone to the incubation tube. R1881 binding was displaced by the addition of excess amounts of T and dihydrotestosterone, but not of estradiol or progesterone. There were no differences between fetal and adult animals. Single point analyses of AR numbers in fetal animals showed significant age and regional differences (P less than 0.05). Since no sex differences were apparent, data from males and females were combined. In the hypothalamus-preoptic area there was a significant increase in AR throughout gestation [1.3 +/- 0.4 (+/- SE) fmol/mg protein; n = 7 (50 days gestation) vs. 6.2 +/- 0.3 fmol/mg protein; n = 4 (150 days of gestation); P less than 0.01]. These values differed significantly from adult male hypothalamic-preoptic area (14.1 +/- 0.3 fmol/mg protein; P less than 0.01; n = 3). AR levels in frontal and temporal cortex were high on day 50 of gestation, but showed a significant decline by day 150 (P less than 0.05). The administration of testosterone propionate (25 mg/kg.day) to pregnant animals from 40-50 days gestation, which resulted in elevated levels of serum T in female, but not male, fetuses had no effect on AR in any brain region studied. These studies confirm the presence of AR in fetal monkey brain. New information is provided on the changes in AR numbers in cortical and hypothalamic tissues during the critical period for sexual differentiation of the primate brain.(ABSTRACT TRUNCATED AT 250 WORDS)

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.