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Membrane-initiated actions of estradiol (E2) in the regulation of LH secretion in ovariectomized (OVX) ewes

J Alejandro Arreguin-Arevalo12, Ryan L Ashley1, Elizabeth R Wagenmaker3, Amy E Oakley34, Fred J Karsch3 and Terry M Nett1*

Author Affiliations

1 Department of Biomedical Science, Colorado State University, Fort Collins, Colorado 80523, USA

2 Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias, Centro de Investigación Regional Golfo Centro, Veracruz, México

3 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA

4 Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA

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Reproductive Biology and Endocrinology 2010, 8:40  doi:10.1186/1477-7827-8-40

Published: 10 May 2010



We demonstrated that E2 conjugated to BSA (E2BSA) induces a rapid membrane-initiated inhibition of LH secretion followed hours later by a slight increase in LH secretion. Whether these actions of E2BSA are restricted to the pituitary gland and whether the membrane-initiated pathway of E2BSA contributes to the up-regulation of the number of GnRH receptors during the positive feedback effect of E2 were evaluated here. We have shown that the suppression of LH secretion induced by E2 and E2BSA is the result of a decreased responsiveness of the pituitary gland to GnRH. In this study we further tested the ability of E2BSA to decrease the responsiveness of the pituitary gland to GnRH under the paradigm of the preovulatory surge of LH induced by E2.


For the first experiment GnRH and LH secretions were determined in samples of pituitary portal and jugular blood, respectively, in ewes treated with 12 mg E2BSA. In the second experiment, the number of GnRH receptors was quantified in ewes 12 h after administration of 25 micrograms E2 (the expected time for the increase in the number of GnRH receptors and the positive feedback effect of E2 in LH secretion) or 12 mg E2BSA. In the third experiment, the preovulatory-like surge of LH was characterized in ewes injected with 25 micrograms E2 alone or followed 8 h later (before the beginning of the LH surge) with 60 mg E2BSA.


a) the decrease in LH secretion induced by E2BSA was not accompanied by changes in the pulsatile pattern of GnRH, b) E2BSA increased the number of GnRH receptors, and c) the presence of E2BSA in E2-treated ewes delayed the onset, reduced the length, and decreased the amount of LH released during the preovulatory surge of LH.


a) the rapid suppression of LH secretion induced by E2BSA is mediated only via a direct action on the pituitary gland, b) E2 acting via a membrane-initiated pathway contributes to increase the number of GnRH receptors and, c) administration of E2BSA near the beginning of the pre-ovulatory surge of LH delays and reduces the magnitude of the surge.