Effect of 2-hydroxyoestradiol on insulin secretion in normal rat pancreatic islets

The possible action of 2-hydroxyoestradiol (2-OHE2) on glucose-induced insu lin secretion was evaluated in pancreatic islets isolated from normal rats by collagenase digestion and incubated in KRB buffer. Insulin output in res ponse to either 3.3 or 16.6 mM glucose was measured by radioimmunoassay in the absence or presence of different concentrations of 2-OHE2 norepinephrin e (NE), or oestradiol. Islets were also incubated with 2-OHE2, NE, or oestr adiol plus a fixed concentration (1 mu M) of the alpha(2)-adrenergic-recept or blocking agent yohimbine. The results showed that 2-OHE2, oestradiol and NE within a range of 0.1 to 20 mu M inhibited glucose-induced insulin secr etion in a dose-dependent manner: K-t (mu M): 0.04 +/- 0.0001, 0.04 +/- 0.0 002 and 0.01 +/- 9.1 E-6 respectively. This suppression was significantly r eversed by yohimbine. Contrary to NE and 2-OHE2, oestradiol at lower concen trations (increasing within a range of 0.001 to 0.05 mu M) in incubation me dium in the same experimental conditions had a significant stimulatory effe ct on insulin secretion. Thus, it would appeart that catecholoestrogens sup press islet insulin release via alpha(2)-adrenergic receptors, which sugges ts that oestrogens may exert a dual modulatory effect on insulin secretion by enhancing release via direct interaction with the cytosolic-oestrogen re ceptor and inhibiting release after their local hydroxylation and the inter action of their new catechol moiety with alpha(2)-adrenergic receptors. Our results suggest that these compounds may play a complementary role to CAs as negative modulators, and they also provide a broader scope far understan ding the effect of oestrogens and/or their metabolites in the control of en docrine functions other than those related to reproduction.