Control of 5α-Reduction of Testosterone in Neuroendocrine Tissues of Female Rats1

Abstract

An assay that involved generating [3H] dihydrotestosterone from [1.alpha.,2.alpha.-3H] testosterone by a microsomal preparation was developed to measure 5.alpha.-reductase (5.alpha.R) activity in brain and pituitary tissues of female rats. A major part of the activity was located within the microsomes and was linear, with protein concentrations ranging from 0.01 to 0.23 mg. The apparent Michaelis-Menten constants for pituitary and hypothalamic-preoptic areas were 2.37 and 2.69 .mu.M respectively. Using this assay, we studied changes in 5.alpha.R activity in brains and pituitaries of female rats ovariectomized 3 days prior to treatment and treated with either vehicle (oil) or estradiol benzoate (E2B, 10 .mu.g/100 g of body weight). Groups of 5-17 animals were killed at 0, 12, 24, 48 and 72 h after treatment. In the pituitary gland, 5.alpha.R activity 48 and 72 h after treatment was twice the value obtained at time 0 (p < 0.05). A single injection of E2B maintained the 5.alpha.R at pretreatment levels (p < 0.05). The 5.alpha.R values for intact females were significantly less than the values obtained from pituitaries of animals treated with estrogen (p < 0.05). This probably indicates that the ovaries control 5.alpha.R through mechanisms other than E2 secretion. In the preoptic area and the hypothalamus, ovariectomy did not produce marked elevations in 5.alpha.R activity (p > 0.05). Thus, the responsiveness of the brain to estrogen treatment differed from the responsiveness of the pituitary. These results confirm the work of others on the effects of ovariectomy and estrogen treatment on 5.alpha.R activity in the brain and pituitary. In addition, the data establish a time course for estrogen action that can be correlated with data on estrogen in the circulation. New data are also provided for understanding short-term effects of estrogen on the brain, effects that may be applicable to the control of gonadotropin secretion in rats.