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Department of Cell Biology, Physiology and Immunology, University of Córdoba, Avda. Menendez Pidal s/n, 14004 Córdoba, Spain
¹ Department of Physiology, University of La Laguna, La Laguna, Spain
² Department of Comparative Pathology, University of Córdoba, Córdoba, Spain

(Requests for offprints should be addressed to J E Sánchez-Criado; Email: fi1sacrj{at}uco.es)

In the rat, administration of tamoxifen (TX) in the absence of oestrogen (E) induces LHRH self-priming, the progesterone receptor (PR)-dependent property of LHRH that increases gonadotrope responsiveness to itself. The oestrogen-dependent PR can be phosphorylated/activated by progesterone (P₄) and, in the absence of the cognate ligand, by intracellular LHRH signals, particularly cAMP/protein kinase A. We have recently found that oestradiol-17ß (E₂), acting on a putative membrane estrogen receptor- in the gonadotrope, inhibits this agonist action of TX. This study investigated the mechanism by which E₂ inhibits TX-elicited LHRH self-priming using both incubated pituitaries from TX-treated ovariectomized (OVX) rats and anterior pituitary cells from OVX rats cultured with TX. It was found that (1) in addition to the inhibitory effect on TX-elicited LHRH self-priming, E₂ blocked P₄ and adenylyl cyclase activator forskolin augmentation of LHRH-stimulated LH secretion, and (2) E₂ did not affect the increasing action of TX on gonadotrope PR expression or pituitary cAMP content. Furthermore, inhibition of protein phosphatases with okadaic acid suppressed E₂ inhibition of TX-elicited LHRH-induced LH secretion, while stimulation of protein phosphatases with ceramide blocked TX-induced LHRH self-priming. Together, these results indicated that membrane ER-mediated E₂ inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases. Results also suggested that the inhibitory effect of E₂on TX-induced LHRH self-priming is exerted through modulation of cellular protein phosphatase activity in the gonadotrope.

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				A. Gordon, J. C Garrido-Gracia, R. Aguilar, S. Guil-Luna, Y. Millan, J. M. de las Mulas, and J. E Sanchez-Criado Ovarian stimulation with FSH reduces phosphorylation of gonadotrope progesterone receptor and LH secretion in the rat Reproduction, January 1, 2009; 137(1): 151 - 159. [Abstract] [Full Text] [PDF]

				A. Gordon, J. C Garrido-Gracia, R. Aguilar, C. Bellido, J. A G. Velasco, Y. Millan, M. Tena-Sempere, J. Martin de las Mulas, and J. E Sanchez-Criado The ovary-mediated FSH attenuation of the LH surge in the rat involves a decreased gonadotroph progesterone receptor (PR) action but not PR expression J. Endocrinol., March 1, 2008; 196(3): 583 - 592. [Abstract] [Full Text] [PDF]

				J. C Garrido-Gracia, A. Gordon, C. Bellido, R. Aguilar, I. Barranco, Y. Millan, J. M. de las Mulas, and J. E Sanchez-Criado The integrated action of oestrogen receptor isoforms and sites with progesterone receptor in the gonadotrope modulates LH secretion: evidence from tamoxifen-treated ovariectomized rats J. Endocrinol., April 1, 2007; 193(1): 107 - 119. [Abstract] [Full Text] [PDF]