Direct effects of progesterone on rat islets of Langerhans in vivo and in tissue culture

Summary Progesterone and oestradiol did not alter rates of insulin secretion from isolated rat islets of Langerhans during a 60 min period of incubation in vitro. However, islets isolated from rats which had been injected daily for 15 days with progesterone (5 mg) and oestradiol (5 g) showed enhanced rates of insulin secretion in response to stimulation by 20 mmol/l glucose or 6 and 20 mmol/l glucose plus 5 mmol/l theophylline. Islets from rats which had been injected with the slow-releasing depot progesterone derivative, hydroxyprogesterone hexanoate, 3 times in 15 days, also showed enhanced rates of insulin release in the absence of any alteration in adenylate cyclase activity. In neither experiment could increased food intake, blood glucose levels or islet insulin content account for the observed changes. The possibility of a direct effect of progesterone on the secretory process was investigated in islets which had been cultured for 20 h with progesterone and oestradiol; these islets were then subjected to a variety of stimuli for secretion. They responded significantly more to glucose (6 or 20 mmol/l) in the presence of theophylline (5 mmol/l), while their insulin content was not significantly different from control islets cultured for a similar period. Islets cultured for 20 h in the presence of progesterone and oestradiol did not show any change in their adenylate cyclase activities. Similarly, direct addition of progesterone and oestradiol to islet homogenates did not alter the adenylate cyclase activity during a 30 minute incubation. These results suggest that progesterone and oestradiol affect insulin secretion directly, by a mechanism which does not involve activation of adenylate cyclase.