Pituitary insulin-like growth factor-I content and gene expression in the streptozotocin-diabetic rat: Evidence for tissue-specific regulation

David Olchovsky, John F. Bruno, Marie C. Gelato, Jinfen Song, Michael Berelowitz

Research output: Contribution to journalArticlepeer-review

Abstract

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 < 0.001 vs. control). Concomitantly, liver and testicular IGF-I mRNA levels were reduced by 90% (P < 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 IGF- I peptide content increased by 69% in STZ-diabetic rats (P < 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.

Original languageEnglish
Pages (from-to)923-928
Number of pages6
JournalEndocrinology
Volume128
Issue number2
DOIs
StatePublished - Feb 1991
Externally publishedYes

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