Hormonal Regulation of Prolactin Cell Development in the Fetal Pituitary Gland of the Mouse

Abstract

The developmental process of prolactin (PRL) cells in the fetal pituitary gland was studied in mice. Although PRL cells were hardly detectable in the pituitary gland of intact fetuses, a treatment with 17beta-estradiol (E(2)) in vitro induced a number of PRL cells that varied drastically in number depending on the stage of gestation with a peak at embryonic d 15. This effect was specific to E(2), with epidermal growth factor, insulin, and forskolin failing to induce PRL cells. Although both estrogen receptor (ER)alpha and ERbeta were expressed in the fetal pituitary gland, the results from ER knockout models showed that only ERalpha mediates E(2) action on PRL cells. A few PRL cells were observed in ERalpha-deficient mice as well as in their control littermates, suggesting that estrogen is not required for the phenotype determination of PRL cells. Unexpectedly, the effect of E(2) on the induction of PRL cells in vitro was diminished after embryonic d 15. Present results suggest that the exposure of fetal PRL cells to glucocorticoids (GCs) results in a reduction of sensitivity to E(2). The mechanism underlying the down-regulation of estrogen sensitivity by GCs was found not to be down-regulation of ER levels, induction of annexin 1, a GC-inducible inhibitor of PRL secretion, or a decrease in the number of PRL precursors by apoptosis. The effect of GCs appeared within 2 h and did not require a de novo protein synthesis. GCs are considered to be involved in the mechanisms of silencing pituitary PRL in gestation possibly through a novel mechanism.

Inhibition of epidermal growth factor receptor stimulates prolactin expression in primary culture of the mouse pituitary gland

“…Our previous studies have revealed that the delayed onset of PRL expression in the mouse pituitary gland is a result of the presence of α‐fetoprotein in the foetal circulation, which binds and inhibits the action of oestrogens, which are strong activators of PRL transcription . Thus far, oestrogens are the only factors able to induce PRL cells in the foetal pituitary gland in mice either in vivo or in vitro . In the present study, we revealed that treatment of foetal pituitary cells with erlotinib and the MAPK kinase inhibitor PD98529 also induced immunocytochemically detectable PRL cells in culture without oestrogen.…”

“…Although pituitary cells other than PRL cells appear in the foetal pituitary gland before parturition, only PRL cells are not detected until after birth in rodents . Our previous studies have revealed that the delayed onset of PRL expression in the mouse pituitary gland is a result of the presence of α‐fetoprotein in the foetal circulation, which binds and inhibits the action of oestrogens, which are strong activators of PRL transcription . Thus far, oestrogens are the only factors able to induce PRL cells in the foetal pituitary gland in mice either in vivo or in vitro .…”

Birthdating studies reshape models for pituitary gland cell specification

“…The lactotrope population was not examined because prolactin expression is estrogen dependent and is not readily detectable until after birth (Ogasawara et al, 2009; Slabaugh et al, 1982). Folliculo-stellate cells are also only detectable post partum, and were not examined in this study (Soji et al, 1997).…”

Use of a prolactin-Cre/ROSA-YFP transgenic mouse provides no evidence for lactotroph transdifferentiation after weaning, or increase in lactotroph/somatotroph proportion in lactation

“…2004)), and by the observation, also in mice, that estrogen can induce PRL cells to appear prior to the onset of GH gene expression on day 15 of fetal life (Matsubara et al . 2001, Ogasawara et al . 2009).…”