Hypothalamic Aromatase Activity in Male and Female Rats during Juvenile Peripubertal Development

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Abstract
Evidence exists that testosterone (T) regulates brain aromatase activity in adult rats. It is not known, however, whether the activity and/or its regulation by androgens change during the time of puberty. In the present study, we examined the change in basal aromatase activity associated with puberty in both male and female rats. We also assessed the influence of castration and treatment with a nonaromatizable androgen, dihydrotestosterone (DHT), on the hypothalamic aromatase system during juvenile and peripubertal development of male rats. Aromatase activity was estimated by both quantifying the 3H2Oreleased from [ 1 β-3H]T and by isolating the estrogen product(s) by thin-layer chromatography (TLC) after incubations with [1,2,6,7-3H]T. 5α-Reductase activity was determined simultaneously in the male hypothalamus by TLC using [1α-3H]Tas the substrate. Aromatase activity was linear with time of incubation and amount of tissue used. It was detected at similar levels in both tissue fragments and acutely dispersed cell preparations. Expression in the latter, but not the former required the addition of NADPH. Intracellular rates of both aromatase and 5α-reductase activities were highest in the mitochondrial-microsomal fraction. In both males and females the time of puberty was associated with a decrease in hypothalamic aromatase activity. In females, this drop was found to occur between the days of first proestrus and first estrus. In males, it occurred between 48 and 68 days of age (i.e., after the animals had reached puberty, as assessed by the presence of free sperm in the seminiferous tubules). Castration of juvenile (28-day-old), peripubertal (48-day-old), and adult (88-day-old), but not young adult (68-day-old) males decreased aromatase activity. DHT treatment restored the activity in the juvenile-peripubertal animals but, like castration, failed to effect the low levels found in the young adults. 5α-Reductase activity also decreased after puberty, but in contrast to aromatase was not altered, at any age studied, by either castration or DHT. The results indicate that: (a) acquisition of male sexual maturity is accompanied by a (transient) loss in the ability of androgens to upregulate hypothalamic aromatase activity, and (b) in both male and female rats completion of puberty is associated with a decline in this activity, which at least in males occurs even in the absence of the gonads. Since 5α-reductase and aromatase activities decrease with puberty, a reduction in the ability of the hypothalamus to metabolize T to its active metabolites is expected. This may represent a factor determining the decreased sensitivity to steroid negative feedback that accompanies the completion of puberty.