title: IGF-I regulates pro-opiomelanocortin and GH gene expression in the mouse pituitary gland.
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 microg/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-17beta (e2; 10(-11) or 10(-9) M) were given for 24 h. 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 microg/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.
authors.affiliation: Department of Biology, Faculty of Science, Okayama University, Tsushima, Okayama 700-8530, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Manabe
authors.forename: R
authors.initials: R
authors.lastname: Matsumura
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D004958:Estradiol; D011333:Pro-Opiomelanocortin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone