REGULATION OF SOMATOSTATIN RECEPTOR MESSENGER-RNA EXPRESSION

The five somatostatin receptor mRNAs are expressed with distinct though overlapping patterns of distribution in the CNS and peripheral tissues. All receptor types are expressed in the anterior pituitary and hypothalamus and could therefore be modulated in states of growth hormone (GH) dysregulation. Metabolic perturbations such as food deprivation and diabetes mellitus lead to suppression of GH levels in the rat, in part due to increased somatostatin tone. In rats deprived of food, pituitary sstr1, 2 and 3 mRNAs were reduced by 80% compared to fed controls; sstr4 and sstr5 mRNAs were unchanged. Hypothalamic sstr mRNA expression was unaltered. In diabetic rats pituitary sstr1, 2 and 3 mRNAs were reduced by 50-80% with sstr1 mRNA restored in part by insulin therapy. Pituitary sstr4 mRNA and hypothalamic expression of these four types was unaffected. sstr5 mRNA is reduced by 70% in the pituitary and by 30% in the hypothalamus with restoration of both by insulin treatment. Altered pituitary sstr expression in food deprivation and diabetes could result from chronic exposure to increased plasma somatostatin. In rat GH(3) pituitary tumour cells exposed to 1 mu M somatostatin for up to 48 h, sstr1, 3, 4 and 5 mRNA increased dramatically while sstr2 mRNA exhibited a biphasic response. We observed a net increase in receptor binding associated with increased sstr mRNA. Somatostatin receptor expression is regulated in a tissue- and type-specific manner, adding further complexity to the action of the multifaceted peptide somatostatin.