A Nongenomic Action of Estradiol as the Mechanism Underlying the Acute Suppression of Secretion of Luteinizing Hormone in Ovariectomized Ewes1

The objective of the present study was to determine how rapidly estradiol (E2) was able to suppress the secretion of LH in ovariectomized (OVX) ewes and to evaluate the ability of conjugated forms of E2 (E2 conjugated to BSA [1,3,5(10)-estratrien-3,17beta-diol-6-one-6-carboxymethyloxime:BSA [E2-BSA] and a novel conjugate, E2 conjugated to a small peptide [E2-PEP]) to mimic the actions of E2 on secretion of LH and FSH. Animals (n = 5-6 per group) were given infusions for 4 h of 50 microg of E2 or equimolar concentrations of E2-BSA or E2-PEP. Treatments with E2, E2-BSA, and E2-PEP each induced an acute suppression of LH secretion (<20 min, P < 0.01). In contrast, E2, but not E2-BSA or E2-PEP, induced the characteristic preovulatory-like surge of LH (at 10 h after priming treatment) and decreased secretion of FSH (at 4 h after priming treatment). In conclusion, the acute inhibition of LH secretion induced by E2 in OVX ewes supports the concept of a nongenomic action as the mechanism underlying the sudden suppression in secretion of LH. In addition, the fact that conjugated forms of E2 mimicked only the acute suppression of secretion of LH, without inducing the putative genomic actions on secretion of LH or FSH (i.e., a preovulatory-like surge), suggests that the acute effect of E2 may be mediated via the plasma membrane.