IGF-I regulates pro-opiomelanocortin and GH gene expression in the mouse pituitary gland

J. Honda, Y. Manabe, R. Matsumura, Sakae Takeuchi, S. Takahashi

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Abstract

IGF-I is expressed in somatotrophs, and IGF-I receptors are expressed in most somatotrophs and some corticotrophs in the mouse pituitary gland. Our recent study demonstrated that IGF-I stimulates the proliferation of corticotrophs in the mouse pituitary. These results suggested that somatotrophs regulate corticotrophic functions as well as somatotrophic functions by the mediation of IGF-I molecules. The present study aimed to clarify factors regulating pituitary IGF-I expression and also the roles exerted by IGF-I within the mouse anterior pituitary gland. Mouse anterior pituitary cells were isolated and cultured under serum-free conditions. GH (0-5 or 1 μg/ml), ACTH (10-8 or 10-7 M), GH-releasing hormone (GHRH; 10-8 or 10-7 M), dexamethasone (DEX; 10-8 or 10-7 M) and estradiol-17β (E2; 10-11 or 10-9 M) were given for 24h. IGF-I mRNA levels were measured using competitive RT-PCR, and GH and pro-opiomelanocortin (POMC) mRNA levels were measured using Northern blotting analysis. GH treatment significantly increased IGF-I mRNA levels (1.5- or 2.1-fold). ACTH treatment did not alter GH and IGF-I mRNA levels. IGF-I treatment decreased GH mRNA levels (0.7-or 0.5-fold), but increased POMC mRNA levels (1.8-fold). GH treatment (4 or 8 μg/ml) for 4 days increased POMC mRNA levels. GHRH treatment increased GH mRNA levels (1.3-fold), but not IGF-I mRNA levels. DEX treatment significantly decreased IGF-I mRNA levels (0.8-fold). E2 treatment did not affect IGF-I mRNA levels. GH receptor mRNA, probably with GH-binding protein mRNA, was detected in somatotrophs, and some mammotrophs and gonadotrophs by in situ hybridization using GH receptor cDNA as a probe. These results suggested that IGF-I expression in somatotrophs is regulated by pituitary GH, and that IGF-I suppresses GH expression and stimulates POMC expression at the transcription level. Pituitary IGF-I produced in somatotrophs is probably involved in the regulation of somatotroph and corticotroph functions.

Original languageEnglish
Pages (from-to)71-82
Number of pages12
JournalJournal of Endocrinology
Volume178
Issue number1
DOIs
Publication statusPublished - Jul 1 2003

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ASJC Scopus subject areas

  • Endocrinology

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