Expression ofmRNA for the estrogen receptor in neonatally androgenized female and castrated male rats
Description
The purpose of this study was to determine whether suppression of female behavioral and physiological characteristics by androgen circulating during critical periods of sexual differentiation involves permanent modifications in the expression of the estrogen receptor mRNA (ER mRNA). The experimental animals were female rats injected with either oil, 50 ug or 1.25 mg testosterone propionate (TP) on postnatal day 4, and male rats castrated at 6 hr, 5 days or 34 days of age. When adults, the animals were injected with oil or 9.9 ug estradiol benzoate (EB), and their brains processed 18 hr later for in situ hybridization, using an $\sp{35}$S-riboprobe complementary to the steroid binding domain of the ER. Computer-derived measures of integrated density and grain counts were obtained in the anteroventral periventricular nucleus (AVPv), the medial preoptic area (MPOA), the arcuate nucleus (Arc), and the ventromedial nucleus (VMH). It was hypothesized that in the aforementioned brain areas basal ER mRNA levels and the degree of down-regulation of ER mRNA expression by EB would be inversely related to the amount of neonatal androgen exposure Basal ER mRNA levels were inversely related to the amount of androgen exposure in female but not in male rats. Statistically significant differences among the oil, 50 ug, and 1.25 mg TP females were obtained in the AVPv and VMH EB significantly decreased the expression of ER mRNA in the AVPv and MPOA of oil-females by 56% and 39% respectively, and that of the 6 hr castrated males by 15% and 39%, respectively. EB decreased ER mRNA expression in the VMH of the 6 hr castrated males by 33%. Neonatal androgen diminished the capacity of EB to down-regulate ER mRNA expression. Additionally, the decrease in ER mRNA expression due to EB differed among the four brain regions The present study demonstrated that ER mRNA expression in the AVPv, a brain region involved in gonadotropin secretion, and in the VMH, an hypothalamic nucleus governing female sexual behavior, is permanently influenced by neonatal androgen. Furthermore, ER mRNA in the AVPv of females, and the MPOA of both female and male rats were most responsive to autologous regulation by estrogen. Thus, early exposure to androgen reduces basal ER mRNA levels, and attenuates the responsiveness of the ER system to estrogen in brain areas associated with ovulation and female sexual behavior