Regulation of proopiomelanocortin gene expression in rat brain and pituitary as studied by in situ hybridization.
The major sites of POMC gene expression are the intermediate and anterior lobes of the pituitary and the arcuate nucleus of the hypothalamus. We have investigated the regulation of POMC mRNA levels in the pituitary and hypothalamus by quantitative in situ hybridization using a 35S-labeled cDNA probe encoding or POMC. In the arcuate nucleus, where the POMC-producing neurons are concentrated, adrenalectomy induced a marked decrease in POMC mRNA levels, an effect that was completely reversed by dexamethasone administration. The stimulating effect of dexamethasone was much more striking in the most caudal regions of the nucleus. Since in the anterior pituitary, glucocorticoids exert an inhibitory action on POMC gene expression, it might be suggested that POMC is differentially regulated by glucocorticoids in the anterior pituitary and the hypothalamus. Ovariectomy induced an increase in mRNA levels in the most rostral region of the arcuate nucleus, an effect that was prevented by the concurrent administration of estradiol or dihydrotestosterone. The role of dopamine was investigated following the administration of the dopaminergic antagonist haloperidol and the D2 dopaminergic receptor agonist bromocriptine. In the arcuate nucleus, bromocriptine increased and haloperidol decreased the hybridization signal. Conversely, in the intermediate lobe of the pituitary, bromocriptine markedly depressed and haloperidol increased the levels of mRNA. These results indicate that the population of POMC neurons in the arcuate nucleus is heterogeneous. They also demonstrate that POMC gene expression is regulated by central and peripheral factors and that this regulation is different in the brain and the pituitary.
MRC Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
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Pelletier
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods*; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats
D005938:Glucocorticoids; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D004298:Dopamine