Steroid feedback on gonadotropin release and pituitary gonadotropin subunit mRNA in mice lacking a functional estrogen receptor α

Steroid hormones regulate levels of gonadotropin mRNA in the pituitary, and gonadotropic hormones in plasma. To determine whether estrogen receptor a (ER alpha) mediates steroid negative feedback, wild type (WT) and estrogen receptor a knockout (ER alpha KO) mice of both sexes were gonadectomized and implanted with a Silastic capsule containing either estradiol (E-2), dihydrotestosterone (DHT), testosterone, or a blank capsule, Ten days later, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levers were measured. Pituitary mRNA levels of gonadotropin subunit (alpha, LH beta, FSH beta) and prolactin (PRL) were quantified, LH levels in gonad-intact ER alpha KO females were elevated, similar to values seen following gonadectomy, By contrast, serum LH concentrations in gonad-intact ER alpha KO males were low and rose following gonadectomy, suggesting androgen feedback, Estradiol treatment significantly decreased plasma LH in WT animals, but not in ER alpha KOs. In fact, in female ER alpha KOs, our dose of E-2 increased plasma levels of LH as compared with untreated, ovariectomized ER alpha KOs, All the steroid treatments suppressed LH in WT animals whereas only DHT consistently suppressed LH concentrations in ER alpha KO mice, The postgonadectomy rise in plasma FSH was prevented by steroid treatments in WT females, but not in any of the other groups. Gonadotropin subunit and PRL mRNA responses to E-2 treatment (both inhibitory and stimulatory) were absent in ER alpha KO mice, suggesting a critical role for ER alpha. Although E-2 can exert negative feedback effects on LH release in both males and females by actions at the ER alpha, the androgen receptor plays the primary physiological role in the male mouse.