A Nongenomic Action of 17(beta)-Estradiol as the Mechanism Underlying the Acute Suppression of Secretion of Luteinizing Hormone

The objective of the present study was to determine the ability of 17(beta)-estradiol (E2) and conjugated forms of E2 (E2 conjugated to BSA [E2-BSA] and a novel conjugate, E2 conjugated to a small peptide [E2-PEP]) to prevent the GnRH-induced secretion of LH and to determine the role of estradiol receptors (ERs) and ER subtypes (ER(alpha), also known as ESR1, and ER(beta), also known as ESR2) in the mediation of the acute action of E2 in primary cultures of ovine pituitary cells. Preincubation of cells for 15 min with E2, E2-BSA, or E2-PEP prevented the GnRH-induced secretion of LH (P < 0.01). Treatment of cells with nonestrogenic steroid hormones did not affect secretion of LH when given alone, nor did these steroids impair the E2-induced inhibition of LH secretion (P > 0.1). Likewise, treatment of cells with the ER-antagonists tamoxifen, hydroxytamoxifen, or ICI 182 780 did not affect (P > 0.1) secretion of LH when given alone but did prevent (P < 0.01) the inhibition by E2 and the E2-conjugates on GnRH-induced secretion of LH. When cells were treated with subtype-selective ER agonists, the ER(alpha) agonist (propylpyrazole-triol), but not the ER(beta) agonist (diarylpropionitrile), decreased (P < 0.01) the GnRH-induced secretion of LH. In conclusion, the rapidity by which E2 prevented GnRH-induced release of LH in ovine pituitary cells suggests that this inhibition is mediated via a nongenomic action of E2. The inhibition of GnRH-induced secretion of LH proved to be steroid specific and mediated by ERs. It may occur specifically through ER(alpha) . The fact that E2-BSA or E2-PEP mimicked the action of E2 suggests that this effect was mediated by an ER associated with the plasma membrane.