Proliferation of pancreatic islet-cells in cyclic and pregnant rats after treatment with progesterone

The effect of progesterone (P) on pancreatic islet-cell proliferation and f unction of cyclic and pregnant rats was investigated in vivo. Silastic tube s containing P were inserted s.c. in cyclic rats for 7 or 14 days and in pr egnant rats from day 7 to 14, from day 14 to 21 or from day 7 to 21 of preg nancy. 5-Bromo-2-deoxyuridine (BrdU) was infused during the last 24 h of th e treatment; the proportion of dividing islet-cells was determined in pancr eatic sections, which were immunostained for BrdU. Islet-cell function was determined by measuring glucose and insulin response to a standard intraven ous glucose challenge. P treatment increased P and 20 alpha-dihydroprogeste rone (20 alpha-OHP) levels in cyclic rats; in pregnant rats, only the plasm a levels of 20 alpha-OHP were elevated. Both 7 and 14 days of P treatment s timulated islet-cell proliferation in cyclic rats. In pregnant rats, P trea tment increased islet-cell proliferation on day 14, but not on day 21 after either 7 or 14 days of P treatment. P did not affect plasma lactogenic act ivity in pregnant rats; plasma concentrations of prolactin were decreased a fter 14 days of P treatment in cyclic rats, but were not affected in pregna nt rats. P treatment had no effect on glucose tolerance and glucose-stimula ted insulin secretion in any of the groups. It was concluded that: 1, in vi vo P stimulates islet-cell proliferation, but does not affect islet-cell fu nction, 2. the stimulatory effects of P are indirect and possibly mediated by the P metabolite 20 alpha-OHP and 3. at the end of gestation, stimulatio n of islet-cell proliferation is inhibited by some factor, which is not ide ntical to P.