Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression

FERRARIS J; BOUTILLON F; BERNADET M; A. SEILICOVICH; GOFFIN V; PISERA D

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

AMER PHYSIOLOGICAL SOC

Año: 2012 vol. 302 p. 356 - 364

0193-1849

Cell turnover in the anterior pituitary (AP) of female rats is coordinated by circulating levels of gonadal steroids. During proestrus the rate of AP apoptosis is the highest and a peak in circulating levels of prolactin (PRL) occurs. Since we have previously demonstrated that PRL exerts autocrine/paracrine actions on AP cells inducing apoptosis and decreasing proliferation, the aim of this study was to investigate the in vivo effect of PRL on female AP cell proliferation and apoptosis rates. The administration of PRL and sulpiride-induced hyperprolactinemia decreased proliferation and increased apoptosis in the AP gland of ovariectomized rats. Apoptosis in the AP gland of female mice was higher at proestrus than at diestrus. These variations were not observed in PRLR KO mice, suggesting that PRL is involved in the peak of AP cell apoptosis that occurs at proestrus. We evaluated if PRL receptor (PRLR) expression varies along the estrous cycle and if PRL regulates its own receptor expression in the AP gland, using female transgenic mice that systemically express PRLR antagonist
1-9-G129R-hPRL. PRLR expression, measured by real time PCR, was variable during the estrous cycle and PRLR antagonism modified the expression of PRLR in an isoform-specific manner. These results suggest that endogenous PRL regulates its AP actions by modifying the expression of PRLR isoforms. Our observations suggest that PRL is involved in the maintenance of cell renewal in the AP that occurs during each estrous cycle in females. Alterations in this physiological role of PRL could contribute to pituitary tumor development.