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

Abstract

In the rat, oestrogen is a key regulator of gonadotrophin synthesis and release through activation of oestrogen receptors (ERs). Gonadotropes express and isoforms of ER and both can activate transcription in response to oestrogen. These experiments were aimed at evaluating the relative contribution of ER and ER 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 agonist propylpyrazole triol (PPT) with or without 1·5, 3·0 or 4·5 mg of the selective ER 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 -like responses. When combined with PPT, DPN attenuated ER 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 and modulated, in a ying-yang fashion, by ER ; and (ii) the oestrogen-dependent exocytosis of LH, the final step in the secretory process, is dependent on ER exclusively.

The integrated action of oestrogen receptor isoforms and sites with progesterone receptor in the gonadotrope modulates LH secretion: evidence from tamoxifen-treated ovariectomized rats

“…Furthermore, it is also possible that the cognate ligand could have partially displaced TX from nuclear ERa because of the pharmacological doses used. Overall, the accumulated evidence from presented and previous data (Sánchez-Criado et al 2004, 2006a suggests that activation of ERb reduces the efficiency of LHRH in stimulating LH release in TX-treated rats.…”

“…These findings indicate that the negative feedback of oestrogen on LH secretion is a genomic ERa effect potentiated by activation of ERb. The expression of PR in the gonadotrope is an oestrogen effect of both E 2 and TX which occurs simultaneously with their negative feedback on LH secretion (Sánchez-Criado et al 2004, 2006a. Gonadotrope PR expression gives rise to a complex phase: the PR-dependent LH surge elicited by an acute rise in E 2 levels (Chappell et al 1999).…”

“…ERa and ERb isoform knockout mice (Pelletier et al 2003, Lindzey et al 2006 are not useful models for the study of ER isoforms interaction either because one or the other ER isoform is lacking. The discovery of ER subtype-selective ligands, such as the ERa agonist propylpyrazole triol (PPT; Stauffer et al 2000), the ERb agonist diarylpropionitrile (DPN; Meyers et al 2001) and the ERa-selective antagonist methyl-piperidino-pyrazole (MPP; Sun et al 2002, Harrington et al 2003, affords useful tools for dissecting the biology of ER subtypes at pituitary level (Sánchez-Criado et al 2004, 2006a in OVX rats. A ying-yang relationship between ERb and ERa on LH secretion has been reported in 2-week OVX rats treated with these ER-selective agonists (Sánchez-Criado et al 2004, 2006a.…”

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland

“…Both ERA (ESR1) and ERB (ESR2) are expressed in the pituitary gonadotrophs and net oestrogen sensitivity in the pituitary critically depends on the balanced expression of ER subtypes. ERA (ESR1) is thought to be the primary mediator of oestrogen-induced reversal of hypertrophied gonadotrophs after ovariectomy (Sanchez-Criado et al 2006). In support of these findings, Era (Esr1)-knockout female mice are completely infertile, have elevated levels of LH and do not ovulate, whereas Erb (Esr2)-knockout mice can ovulate, although they are sub-fertile (Hewitt & Korach 2003).…”

Influência do hormônio tireoideano na atividade do gonadotrofo.

“…A análise morfológica do gonadotrofo revelou aumento do número de células imunorreativas ao β LH, associado a um conteúdo citoplasmático difuso e granular de fluorescência intensa. Alterações estas compatíveis com o estímulo celular (WATANABE et al, 1998;SANCHEZ-CRIADO et al, 2006;KITAHARA et al, 2007;SORENSON et al, 2007;GARRIDO-GRACIA et al, 2008).…”