Effect of Prolactin Proteolytic Fragments, Vasoinhibins, on Anterior Pituitary cell proliferation and Apoptosis

FERRARIS JIMENA; RADL DANIELA; ZÁRATE SANDRA; JAITA GABRIELA; BOTI VALERIA; EIJO GUADALUPE; MAGRI LAURA; ZALDIVAR VERÓNICA; SEILICOVICH ADRIANA; CLAPP CARMEN; PISERA DANIEL

San Diego

Congreso; 92nd Annual Meeting of the Endocrine Society; 2010

The anterior pituitary gland is under a constant cell turnover. In female rats, this process appears to be coordinated by the circulating levels of gonadal steroids. During proestrus, when the apoptosis rate of anterior pituitary cells is the highest, a peak in circulating levels of prolactin occurs. This hormone may be cleaved to different fragments (vasoinhibins) and their production varies along the estrous cycle.  Proteolysis of rat prolactin by cathepsin D produces a single 16-kDa vasoinhibin (Vi) whith antiangiogenic actions, inhibiting proliferation and inducing apoptosis of endothelial cells. The aim of this study was to investigate the effects of Vi on apoptosis and proliferation of anterior pituitary cells. In primary cultures of anterior pituitary cells we observed by Western Blot the presence of Vi in both media and cell extracts. A recombinant preparation of Vi (10 and 100 nM) induced apoptosis (determined by FACS) of anterior pituitary cells from ovariectomized rats (apoptotic cells, media ± SE. Control (C): 16.7 % ± 2.0; Vi 10 nM 24.1 % ± 1.5, p<0.01; Vi 100 nM 23.4 % ± 0.3, p<0.05, Dunnet). This effect was not observed when the cells were cultured in the presence of estradiol (E2, 10-9 M). In addition, Vi (10 nM) decreased forskolin-induced proliferation (evaluated by BrdU incorporation) in total anterior pituitary cells and lactotropes (% of BrdU positive cells) when the cells were cultured without E2 (Total: C: 5.0 %; Vi 2.2%; Lactotropes: C: 8.1 %; Vi 2.9 %, p<0.01, ÷2) or  with E2 (Total: C: 5.4 %; Vi 0.8 %. p< 0.01. Lactotropes: C: 8.3 %; Vi 1.3 %, p<0.01; ÷2). These results suggest that vasoinhibins are present in anterior pituitary gland and that they could be involved in the control of anterior pituitary cell population by inducing apoptosis and inhibiting proliferation.