PARENT SESSION

(T650) MORPHOLOGICAL STUDY OF GONADOTROPIN-SECRETING CELLS IN OVARIECTOMIZED RATS TREATED WITH DIFFERENT ESTROGEN RECEPTOR (ER) LIGANDS: A ROLE FOR ER IN THE GONADOTROPE?

Sanchez-Criado, Jose¹, Martin de las Mulas, Juana¹, Navarro, Victor¹, Bellido, Carmen¹, Aguilar, Rafaela¹, Garrido-Gracia, Jose¹, Tena-Sempere, Manuel¹, Blanco, Alfonso¹, ¹ University of Cordoba, Cordoba, Spain

ABSTRACT- Estrogen (E) is a key regulator of gonadotropin secretion (synthesis and release) through activation of ER. Gonadotropes express and isoforms of ER and both can activate transcription in response to E. The aim of these experiments was to evaluate the relative contribution of activation of ER and ER in the gonadotrope function. Two-week ovariectomized (OVX) rats were injected over three days with 25 g estradiol benzoate (EB), 0.3 or 1.5 mg of the selective ER agonist PPT with or without 1.5, 3.0 or 4.5 mg of the selective ER agonist DPN, DPN alone and 0.3 or 3 mg of the SERM tamoxifen (TX). Controls were given 0.2 ml oil. Serum concentration of LH and FSH, gonadotrope progesterone receptor (PR) expression, pituitary PR content, and gonadotrope morphology were analyzed by RIA, immunohistochemistry, Western blotting and light and electron microscopy, respectively. Results showed that whereas PPT restored the negative feedback on gonadotropin release, induced PR expression, and reverted the effects of OVX on gonadotrope size and morphology of the membranous cytoplasm (RER, Golgi complex and secretory granules), DPN alone activated all secretory morphological aspects of the secretion of gonadotropins except exocytosis. When DPN was combined with PPT, it reduced, in a dose-dependent manner, the positive effects of PPT on the synthesis apparatus without interfering with the PPT releasing activity. Thus, the moderate effect of the cognate ligand (EB) on the gonadotrope synthesis apparatus seen in these experiments can be interpreted as a result of simultaneous activation of both ER isoforms. In addition, TX, whose agonistic action on LH secretion is exerted through ER subtype, had positive effects on both synthesis and release processes. It is suggested that (1) the isoforms ER and ER are not components of a redundant regulatory system at the gonadotrope; (2) the synthesis of gonadotropins is stimulated by ER and modulated by ER in a ying-yang relationship; and (3) the release of gonadotropins, the final step of the secretory process, is dependent on ER exclusively

KEY WORDS: estrogen receptor, estrogen receptor ligands, gonadotropins, progesterone receptor