Pituitary insulin-like growth factor-I content and gene expression in the streptozotocin-diabetic rat: evidence for tissue-specific regulation.
 Insulinopenic diabetes mellitus in the rat is associated with reduced circulating levels of insulin-like growth factor-I (IGF-I), resulting primarily from decreased IGF-I synthesis in liver and extrahepatic sites.
 Plasma GH levels in these animals are also suppressed, with loss of episodic secretion and decreased pituitary synthesis.
 Intrapituitary IGF-I has been postulated to exert local autocrine/paracrine negative feedback regulation on GH synthesis and secretion.
 The present studies were designed to examine regulation of pituitary IGF-I peptide content and gene expression in insulinopenic streptozotocin (STZ)-diabetic rats compared to that in liver and testis.
 Serum IGF-I levels were reduced by 86% in STZ-diabetic rats together with reduction of IGF-I content in liver (53%) and testis (74%; all P less than 0.001 vs.
 control).
 Concomitantly, liver and testicular IGF-I mRNA levels were reduced by 90% (P less than 0.001 vs.
 control).
 Insulin treatment restored IGF-I peptide levels in serum, liver, and testis toward normal, with a partial but significant increase in liver IGF-I mRNA.
 In contrast, pituitary IFG-I peptide content increased by 69% in STZ-diabetic rats (P less than 0.001 vs.
 control), with no change in IGF-I gene expression.
 Insulin treatment completely reversed the rise of pituitary IGF-I peptide content.
 These results demonstrate a novel discordance in the regulation of IGF-I gene expression and peptide content between pituitary and other tissues in STZ-induced diabetic rats.
 Elevated IGF-I levels in the pituitaries of these animals may partly explain the suppressed GH synthesis and secretion seen in STZ-diabetic rats and provide further evidence for a potential autocrine or paracrine role of pituitary IGF-I in GH regulation.
