Progesterone stimulates pancreatic cell proliferation in vivo

Abstract

Treatment of cyclic and pregnant rats with progesterone stimulates cell proliferation within the islets of Langerhans. It was investigated whether this effect of progesterone depends on sex and/or the presence of the gonads or the presence of oestradiol. For this purpose, Silastic tubes containing progesterone were inserted s.c. in intact and gonadectomized male and female rats, and in gonadectomized female rats treated with oestradiol. After 6 days of progesterone treatment, rats were infused for 24 h with 5-bromo-2 0 -deoxyuridine (BrdU) and dividing cells were identified in pancreatic sections by immunostaining for BrdU. Progesterone treatment increased islet-cell proliferation in intact male and female rats (P<0.05), but not in gonadectomized male and female rats or in gonadectomized female rats supplemented with oestradiol. Furthermore, in intact male and female rats, progesterone treatment also stimulated cell proliferation in extra-islet pancreatic tissue (P<0.05). Identification of the proliferating cells, by double-immunocytochemistry, revealed that progesterone treatment stimulated proliferation of both a and b cells within the pancreatic islets. In extra-islet pancreatic 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 insulincontaining cells outside the pancreatic islets, nor that of cytokeratin 20/insulin double-positive cells, suggesting that progesterone treatment did not stimulate differentiation 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). It is concluded that progesterone stimulates pancreatic cell proliferation indirectly; gonadal factor(s), not identical to oestradiol, is (are) probably involved.

Role of 17beta-estradiol and/or progesterone on insulin sensitivity in the rat: implications during pregnancy

“…Our results therefore seem to indicate that 17 -estradiol is responsible for the increase in insulin secretion. Our findings might agree with several studies reporting that ovarian steroids affect -cell function and glucose homeostasis by increasing insulin production through the induction of -cell hypertrophy (YkiJarvinen 1984, Magnaterra et al 1997, Zhu et al 1998, Nieuwenhuizen et al 1999 and, furthermore, with those observing that chronic progesterone therapy has no effect on either basal glucose or insulin levels compared with control rats (Nelson et al 1994). We have previously demonstrated (González et al 1997(González et al , 1998) that the fasting serum insulin levels decreased between days 5 and 10 and increased between days 10 and 15 of pregnancy, findings in line with other studies (Bliss et al 1990, Parsons et al 1992, Muñoz et al 1995.…”

Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor

“…Of interest, progesterone slightly increased these functions in a preliminary study, and megestrol acetate (MA), a progesterone derivative, has strong stimulatory effects on ASCs. In previous studies, progesterone increased the proliferation of mammary gland and pancreatic cells [19,20]. In addition, progesterone stimulated the proliferation of steroid receptor-positive breast cancer and increased the migration of breast cancer cells [21,22].…”

“…After 2 hours, MA (10 mM) or RU486 (10 mM) in a-MEM containing 0.2% FBS was added on the lower side of the Transwell membrane plates for [16][17][18][19][20] hours. The migrated cells remaining in the Transwell membrane were fixed with ice-cold methanol for 20 minutes.…”

The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss

“…1C). Female hormones may contribute to delaying diabetes, as progesterone increases beta cell mass during pregnancy (12). Because beta cell reductions precede hyperglycemia in female DKO mice, beta cell loss does not appear to result from hyperglycemia.…”