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

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

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

AMER PHYSIOLOGICAL SOC

Año: 2012 p. 356 - 364

0193-1849

Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of prolactin receptor. In order to determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist ∆1-9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild type littermates. In addition, blockade of prolactin receptor in vitro by ∆1-9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of long isoform of prolactin receptor, measured by real time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only modest increase of S3 short isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development.