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Journal of Endocrinology (2006) 188, 167-177    DOI: 10.1677/joe.1.06377
© 2006 Society for Endocrinology

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Gonadotropin-secreting cells in ovariectomized rats treated with different oestrogen receptor ligands: a modulatory role for ERß in the gonadotrope?

J E Sánchez-Criado*, J Martín de las Mulas1,*, C Bellido, V M Navarro, R Aguilar, J C Garrido-Gracia, M M Malagón, M Tena-Sempere and A Blanco1

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

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

* (J E Sánchez-Criado and J Martín de las Mulas contributed equally to this work)

In the rat, oestrogen is a key regulator of gonadotrophin synthesis and release through activation of oestrogen receptors (ERs). Gonadotropes express {alpha} and ß isoforms of ER and both can activate transcription in response to oestrogen. These experiments were aimed at evaluating the relative contribution of ER{alpha} and ERß on gonadotrope morphology, progesterone receptor (PR) expression and LH secretion. Ovariectomized rats were daily injected over 3 days with 25 µg oestradiol benzoate, 0.3 or 1.5 mg of the selective ER{alpha} agonist propylpyrazole triol (PPT) with or without 1.5, 3.0 or 4.5 mg of the selective ERß agonist diarylpropionitrile (DPN), DPN alone, and 0.3 or 3 mg of tamoxifen. Controls were given 0.2 ml oil. Serum concentration and pituitary content of LH, gonadotrope PR expression, pituitary PR content, and gonadotrope morphology were analyzed by RIA, immunohistochemistry, Western blotting and light and electron microscopy, respectively. Results showed that PPT reversed all consequences of ovariectomy, DPN mimicked the effects of PPT except for its LH-releasing action and tamoxifen had ER{alpha}-like responses. When combined with PPT, DPN attenuated ER{alpha} effects without interfering with its LH-releasing activity. Oestradiol benzoate had similar effects to those of combined PPT and DPN. It is suggested that (i) the structural reorganization of the cytoplasmic organelles provided by oestrogen, and the shrinkage of the ovariectomy-induced hypertrophy of gonadotropes, which precedes the expression of PR, are evoked by ER{alpha} and modulated, in a ying–yang fashion, by ERß; and (ii) the oestrogen-dependent exocytosis of LH, the final step in the secretory process, is dependent on ER{alpha} exclusively.




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