title: Increases in preproenkephalin mRNA levels in the Syrian hamster: the influence of glucocorticoids is dependent on age and tissue.
abstract: In adult hamsters, basal proenkephalin (Penk) gene expression in adrenals is independent of glucocorticoids and glucocorticoid receptor blockade, by RU 486, increases striatal preproenkephalin (PPenk) mRNA levels. However, glucocorticoids maintain both basal and induced Penk gene expression in rat adrenal (medulla) and striatum. This suggests species and tissue-specific differences in Penk gene regulation. Since studies show temporal coordination in Penk gene expression in developing hamster adrenal and striatum, we tested the hypothesis that increasing PPenk mRNA levels are dependent, while basal levels are independent of glucocorticoids in developing hamsters. To facilitate this study, we examined the influence of glucocorticoids on the temporal increases in developing hamster PPenk mRNA observed in adrenals between postnatal days 0 and 4 and in striatum between postnatal days 12 and 48. PPenk mRNA levels were determined in hamster pups after treatment with increasing doses of metyrapone (an 11beta hydroxylase inhibitor) or with the glucocorticoid receptor antagonist RU 486 +/- metyrapone between postnatal days 2 and 4. Levels were also determined 36 days after hypophysectomy at age 16-17 days. Although plasma glucocorticoid levels and/or the influence from glucocorticoids were reduced, only developmental increases in PPenk mRNA are influenced by glucocorticoids in hamster adrenals, while basal adrenal mRNA levels are unchanged. However, pituitary influence on striatal PPenk mRNA levels appears complex and may involve steroid and/or non-steroid factors. These results suggest that glucocorticoids regulate hamster Penk gene expression via a mechanism that varies with age and tissue and functions during the induction of the Penk gene and not to maintain basal gene expression. Possible mechanisms and species variation are discussed.
authors.affiliation: Program in the Neuroscience of Drug Abuse, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, 27707, USA. sfranklin@nccu.edu
authors.forename: Steven O
authors.initials: SO
authors.lastname: Franklin
authors.forename: Rosa
authors.initials: R
authors.lastname: Jimenez
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007016:Hypophysectomy / Q000379:methods; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D004745:Enkephalins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006727:Hormone Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D015735:Mifepristone; C033660:preproenkephalin; D010625:Phenylethanolamine N-Methyltransferase; D008797:Metyrapone