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

ABSTRACT

The possible action of 2-hydroxyoestradiol (2-OHE2) on glucose-induced insulin secretion was evaluated in pancreatic islets isolated from normal rats by collagenase digestion and incubated in KRB buffer. Insulin output in response to either 3.3 or 16.6 mM glucose was measured by radioimmunoassay in the absence or presence of different concentrations of 2-OHE2, norepinephrine (NE), or oestradiol. Islets were also incubated with 2-OHE2, NE, or oestradiol plus a fixed concentration (1 microM) of the alpha 2-adrenergic-receptor blocking agent yohimbine. The results showed that 2-OHE2, oestradiol and NE within a range of 0.1 to 20 microM inhibited glucose-induced insulin secretion in a dose-dependent manner Ki (microM) 0.04 +/- 0.0001, 0.04 +/- 0.0002, and 0.01 +/- 9.1 E-6 respectively. This suppression was significantly reversed by yohimbine. Contrary to NE and 2-OHE2, oestradiol at lower concentrations (increasing within a range of 0.001 to 0.05 microM) in incubation medium in the same experimental conditions had a significant stimulatory effect on insulin secretion. Thus, it would appear that catecholoestrogens suppress islet insulin release via alpha 2-adrenergic receptors, which suggests that oestrogens may exert a dual modulatory effect on insulin secretion by enhancing release via direct interaction with the cytosolic-oestrogen receptor and inhibiting release after their local hydroxylation and the interaction 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 for understanding the effect of oestrogens and/or their metabolites in the control of endocrine functions other than those related to reproduction.