TY - JOUR
T1 - Pituitary insulin-like growth factor-I content and gene expression in the streptozotocin-diabetic rat
T2 - Evidence for tissue-specific regulation
AU - Olchovsky, David
AU - Bruno, John F.
AU - Gelato, Marie C.
AU - Song, Jinfen
AU - Berelowitz, Michael
PY - 1991/2
Y1 - 1991/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026073385&partnerID=8YFLogxK
U2 - 10.1210/endo-128-2-923
DO - 10.1210/endo-128-2-923
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AN - SCOPUS:0026073385
VL - 128
SP - 923
EP - 928
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 2
ER -