Modulatory effect of ghrelin in prepubertal porcine ovarian follicles.

Ghrelin is a novel growth hormone-releasing peptide, originally identified in rat stomach as an endogenous ligand of the growth hormone secretagogue receptor. Ghrelin is an important regulator of growth hormone secretion, food intake, and reproductive function. This study investigates whether or not ghrelin can modulate prepubertal pig ovary function, which was measured as ovarian estradiol secretion, aromatase activity, cell proliferation, and apoptosis. To investigate this, ovarian cells were co-cultured with four different doses of ghrelin (100, 250, 500, and 1000 pg/ml) for 48 h. Culture media samples were collected, and estradiol levels were determined, while aromatase expression was measured in the cultured cells. Cell apoptosis was measured by determination of caspase-3 activity, DNA fragmentation and TUNEL assay. Ghrelin in 250 and 500 pg/ml doses stimulated estradiol secretion. At all doses ghrelin stimulated aromatase activity and protein expression. Moreover, ghrelin increased cell proliferation and decreased apoptosis. This study provides novel evidence that ghrelin has a modulatory effect in the ovary. We suggest two mechanisms that explain how ghrelin acts on estradiol secretion: 1) ghrelin directly influences aromatase activity and protein expression; 2) ghrelin stimulates cell proliferation and antiapoptotic actions.