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

Steroid hormones regulate levels of gonadotropin mRNA in the pituitary, and gonadotropic hormones in plasma. To determine whether estrogen receptor a (ERα) mediates steroid negative feedback, wild type (WT) and estrogen receptor a knockout (ERαKO) mice of both sexes were gonadectomized and implanted with a Silastic capsule containing either estradiol (E₂), dihydrotestosterone (DHT), testosterone, or a blank capsule. Ten days later, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured. Pituitary mRNA levels of gonadotro-pin subunit (α, LHβ, FSHβ) and prolactin (PRL) were quantified. LH levels in gonad-intact ERαKO females were elevated, similar to values seen following gona-dectomy. By contrast, serum LH concentrations in gonad-intact ER a KO males were low and rose follow-ing gonadectomy, suggesting androgen feedback. Estradiol treatment significantly decreased plasma LH in WT animals, but not in ER a KOs. In fact, in female ER a KOs, our dose of E₂ increased plasma levels of LH as compared with untreated, ovariectomized ER a KOs. All the steroid treatments suppressed LH in WT ani-mals whereas only DHT consistently suppressed LH concentrations in ER a 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 E₂ treatment (both inhibitory and stimulatory) were absent in ER a KO mice, suggesting a critical role for ERα. Although E₂ can exert negative feedback effects on LH release in both males and females by actions at the ERα, the androgen receptor plays the primary physiological role in the male mouse.