LACTATIONAL CHANGES IN THE RAT EXOCRINE PANCREAS SOMATOSTATIN RECEPTORS AND MODULATION OF GUANYLATE-CYCLASE

Hyperplasia of the pancreatic tissue during late lactation (third week )and lasting for at least the first two weeks after weaning has been o bserved by several authors. Since the tetradecapeptide somatostatin (S S) inhibits pancreatic growth and its plasma levels are elevated durin g these periods, the aim of the present study was to determine the pos sible implication of the somatostatinergic system in the pancreatic ch anges cited above. Thus, the present study investigated I-125-Ty(11)-s omatostatin (I-125-Tyr(11)-SS) binding and the effects of SS on guanyl ate cyclase activity as well as pancreatic somatostatin-like immunorea ctivity (SSLI) levels in pancreatic acinar membranes from control, lac tating and weaning rats. SS receptors were identified using I-125-Tyr( 11)-SS and isolated pancreatic acinar membranes in vitro. There was an increase in the number of SS receptors after the third week of lactat ion (244 +/- 6 vs. 155 +/- 12 fmol/mg protein, P < 0.01) and the first two weeks after weaning (327 +/- 8 vs. 164 +/- 10 fmol/mg protein, P < 0.001). No change in the affinity of the receptor site was detected at either study time. In addition, SS-stimulated guanylate cyclase act ivity was markedly increased at the third week of lactation (119%) and at the second week after weaning (158%) when compared with the contro l group. In contrast, basal guanylate cyclase activity was not modifie d at either study period. Thus, SS-stimulated guanylate cyclase activi ty is increased in pancreatic acinar membranes at late lactation and a t the second week after beginning weaning probably due to an increase in the number of SS receptors. Significant decreases in SSLI content w ere observed at the third week of lactation (69%) and the second week after weaning (37%) when compared with the respective controls. The pr esent results suggest that pancreatic acinar cell growth observed at t he third week of lactation and the second week after weaning is associ ated with up-regulation of SS receptors which would represent a mechan ism promoted by the cell that would negatively regulate the mitogenic activity of the increased number of pancreatic growth factors observed during both periods.