Morphological Studies of Prolactin-Secreting Cells in Estrogen Receptor α and Estrogen Receptor β Knockout Mice

Abstract

Estrogens play a major role in the regulation of prolactin (PRL) secretion through activation of pituitary and hypothalamic estrogen receptors (ERs). In order to evaluate the relative role of ERα and ERβ in the control of PRL density in the pituitary gland, we performed immunocytochemical localization of PRL and ERs in pituitaries of wild-type (WT), ERα knockout (KO) and ERβKO mice. In WT and ERβKO anterior pituitaries, the vast majority of secretory cells contained ERα immunoreactivity, while no ERα immunostaining could be found in ERαKO pituitaries. No ERβ immunoreactivity could be detected in pituitaries of WT, ERαKO or ERβKO mice. At the light microscopic level, a large number of cells staining for PRL were present in pituitaries of female WT, while in female ERαKO pituitaries, the density of PRL cells was much lower. In WT male pituitaries, the density of PRL cells was lower than observed in female WT, while PRL staining was markedly decreased in male ERαKO as compared to male WT. In ERβKO mice of both sexes, the results were identical to those observed in WT animals. At the electron microscopic level, in WT mice of both sexes, type 1 PRL cells exhibited a well-developed Golgi apparatus and a large number of strongly stained large mature and immature secretory granules. Type 2 PRL cells were also present in the pituitary. Type 2 PRL cells contain small poorly labelled granules. In ERαKO mice of both sexes, type 1 PRL cells were atrophied with poorly developed Golgi apparatus, and no type 2 PRL cells could be observed. In ERαKO pituitaries, typical gonadectomy cells were found. No ultrastructural changes were observed in PRL cells of ERβKO mice. The present data strongly suggest that the positive regulation of PRL expression at the pituitary level by estrogens is mediated by ERα and does not involve ERβ activation.

The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary

“…Several factors involved in PRL cell proliferation and differentiation have been investigated using knockout (KO) techniques. In adult insulin-like growth factor 1 (IGF1) KO (IGF1KO) and estrogen receptor 1 (Esr1) KO mice, PRL cells are decreased in number (Stefaneanu et al 1999, Pelletier et al 2003. Therefore, IGF1 and estrogen are suggested to influence PRL cell proliferation and differentiation in postnatal life.…”

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

“…Since E 2 activates the complete ER orchestra in the gonadotrope, it is difficult to chart separately the specific role of each ER pool on LH secretion using either intact cyclic or ovariectomized (OVX) rats treated with the cognate ligand. 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.…”

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

“…The pharmacological doses of EB used in the present experiment shrinks gonadotropes almost to the size exihibited by pituitaries in intact, proestrous rat (Sánchez-Criado et al 2005). The respective roles of ER and ER in prolactin-and gonadotrophin-secreting cells have previously been investigated through the use of ER-knockout mice (Pelletier et al 2003). However, the lack of either ER or ER in ER-knockout models limits the study of physiological interaction between ER isoforms.…”