Prenatal inhibition of aromatase activity affects luteinizing hormone feedback mechanisms and reproductive behaviors of adult guinea pigs.

The necessity of brain aromatization for sexual differentiation was investigated by treating pregnant guinea pigs with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), from Day 30 to Day 55 of gestation. In postnatal Week 16, subjects were gonadectomized, and blood samples were collected after treatment with 10 micrograms estradiol benzoate (EB), used to elicit an LH surge; subjects were subsequently treated with GnRH to test pituitary responsiveness. Plasma samples were assayed for LH by RIA. Prenatal ATD treatment did not affect the organization of the LH surge mechanism in either male or female subjects. All animals, regardless of sex or treatment, released LH after GnRH treatment, but the responsiveness of the gonadotroph to GnRH was attenuated in both males and females treated with ATD in utero. In addition, a significant sex difference in the pattern of LH released in response to a GnRH challenge was found. ATD-treated animals did not respond to the negative feedback actions of EB on LH secretion (p < 0.05), and the percentage of males displaying lordosis behavior was greater in this group than in controls (p < 0.05). Mounting behavior and lordosis behavior of females were not significantly affected by treatment. These data demonstrate a need for estrogen in the organization of brain areas that mediate negative feedback control of LH in both sexes and lordosis behavior in the male guinea pig. The organization of positive feedback mechanisms for controlling LH seems to be under androgenic control. Our data also suggest that the responsiveness of the gonadotroph to GnRH action is developmentally coordinated by prenatal estrogen and is sexually differentiated.