Progesterone stimulates pancreatic cell proliferation in vivo

Treatment of cyclic and pregnant rats with progesterone stimulates cell pro liferation within the islets of Langerhans. It was investigated whether thi s effect of progesterone depends on sex and/or the presence of the gonads o r the presence of oestradiol, For this purpose, Silastic tubes containing p rogesterone were inserted s.c. in intact and gonadectomized male and female rats, and in gonadectomized female rats treated with oestradiol, After 6 d ays of progesterone treatment, rats were infused for 24 h,with 5-bromo-2'-d eoxyuridine (BrdU) and dividing cells were identified in pancreatic section s by immunostaining for BrdU. Progesterone treatment increased islet-cell p roliferation in intact male and female rats (P<0.05), but not in gonadectom ized male and female rats or in gonadectomized female rats supplemented wit h oestradiol. Furthermore, in intact male and female rats, progesterone tre atment also stimulated cell proliferation in extra-islet pancreatic tissue (P<0.05), Identification of the proliferating cells, by double-immunocytoch emistry, revealed that progesterone treatment stimulated proliferation of b oth alpha and beta cells within the pancreatic islets, In. extra-islet panc reatic tissue, progesterone treatment stimulated proliferation in both duct (cytokeratin 20-immunoreactive) and non-duct cells. Progesterone treatment did not increase the number of single glucagon or insulin-containing cells outside the pancreatic islets, nor that of cytokeratin 20/insulin double-p ositive cells, suggesting that progesterone treatment did not stimulate dif ferentiation of duct cells into endocrine cells. Progesterone treatment did not affect insulin responses to an i.v. glucose load (0.5 g/kg body weight ). II is concluded that progesterone stimulates pancreatic cell proliferati on indirectly; gonadal factor(s), not identical to oestradiol, is (are) pro bably involved.