Role of prolactin in anterior pituitary cell renewal

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

Congreso; 93º Annual Meeting of the Endocrine Society; 2011

The anterior pituitary (AP) gland is under a constant cell turnover. In female rats, this process appears to be coordinated by circulating levels of gonadal steroids (1). During proestrus, when AP apoptosis rate is the highest, a peak in circulating levels of prolactin (PRL) occurs. PRL receptor (PRLR) KO mice show an increase in pituitary weight and it was observed that PRL decreases lactotroph proliferation in vitro (2). Our hypothesis is that PRL participates in AP cell turnover, regulating proliferation and/or apoptosis rates. The aim of this study was to investigate the effect of endogenous PRL on AP proliferation and apoptosis. Wild type (WT) and transgenic mice (TG) expressing the pure PRLR antagonist del1-9-G129R-hPRL (3) were injected with bromodeoxyuridine (BrdU). Pituitary were obtained, weighed and processed to evaluate the proliferation (BrdU incorporation by immunohistochemical detection) and apoptotic rates (TUNEL assay). In females, there was no difference of pituitary weight between both genotypes. In contrast, pituitary weight of male TG mice was higher than those from WT mice (WT 1.89 mg ±0.06, TG 2.23 mg ±0.16, p<0.05 Mann Whitney test). AP proliferation index was higher in male TG mice than in WT males (WT 0.083%, TG 0.19%, p<0.01, c2), whereas in female TG mice the percentage of BrdU positive cells decreased with respect to WT females (WT 1.28% TG 0.57%, p<0.01 c2). The apoptotic index was not different between WT and TG male or WT and TG female mice. PRL activity is mediated by different PRLR subtypes, and their expression could be modulated by gonadal steroids (3). We investigated expression of the various PRLR isoform in AP along the estrous cycle in females. Also, we studied the effect of PRLR antagonist on PRLR expression (long and short isoforms S1, S2, S3). Quantitative PCR was performed using  specific primers for each PRLR isoform (4). The main isoform expressed in male and female AP is the long isoform, in contrast to the liver where the short isoform predominates. The presence of the PRLR antagonist modified the expression of PRLR isoforms in AP of both genders. In females, we also observed that the ratio of long versus short isoforms fluctuated along the estrous cycle. In summary, the chronic blockade of PRLR induces changes in AP cell proliferation indicating that PRL is involved in AP cell renewal. Additionally, changes in AP PRLR expression observed in TG mice suggest a regulatory role of PRL on its own activity in the AP.