Developmental regulation of proopiomelanocortin gene expression in the fetal and neonatal rat pituitary
| Autor: | John E. Pintar, Roderick E. M. Scott |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
endocrine system
Pituitary gland medicine.medical_specialty Pro-Opiomelanocortin Transcription Genetic Corticotropin-Releasing Hormone 8-Bromo Cyclic Adenosine Monophosphate Biology Dexamethasone Rats Sprague-Dawley chemistry.chemical_compound Fetus Endocrinology Glucocorticoid receptor Proopiomelanocortin Internal medicine Gene expression medicine Animals Androstanols RNA Messenger Molecular Biology digestive oral and skin physiology Nucleic Acid Hybridization Nuclease protection assay Exons General Medicine Introns Rats medicine.anatomical_structure Animals Newborn Gene Expression Regulation nervous system RU-28362 chemistry Hypothalamus Pituitary Gland biology.protein RNA Heterogeneous Nuclear Solution hybridization hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Endocrinology. 7:585-596 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/mend.7.4.8502239 |
| Popis: | Expression of the POMC gene and secretion of its peptide products are under complex regulation in the pituitary by multiple factors. CRF stimulates POMC transcription and secretion in both adult anterior (AL) and intermediate (IL) pituitary lobes, whereas glucocorticoids have an inhibitory effect on POMC in the AL, but little, if any, effect in the IL. To determine when transcriptional responses elicited by these factors begin during development and whether they undergo changes during ontogeny, we used a solution hybridization/nuclease protection assay with a POMC exon 1-intron A splice junction probe to analyze simultaneously the levels of intron A-containing POMC heterogeneous nuclear RNA (hnRNA) and POMC mRNA in explant fetal and neonatal rat pituitaries. We examined responses to 8-bromo-cAMP, CRF, and dexamethasone (dex) at stages before and after innervation of the IL by dopaminergic neurons from the hypothalamus. Treatment of embryonic day 15 (e15) whole pituitaries with CRF (10(-7) M) for 1 h led to a 2.5-fold increase in the level of POMC hnRNA, while pretreatment with dex (10(-6) M) inhibited the CRF-induced stimulation of POMC transcription. These results demonstrate that by e15, POMC transcription is already responsive to both CRF and dex, and thus, functional receptors (coupled effectively to the POMC promoter) are present by this age. Initial studies of POMC mRNA levels at early postnatal ages showed that 1 mM 8-bromo-cAMP stimulated postnatal day 1 (p1) and p10 AL and neurointermediate lobe (NIL) POMC mRNA levels, and 10(-6) M dex inhibited this stimulation in p1 AL, p10 AL, and p1 NIL, but not in p10 NIL. These studies were extended to examine POMC hnRNA responses at these ages. Treatment with CRF for 1 h increased POMC hnRNA 1.9- and 1.5-fold in p1 and p10 AL, respectively, and pretreatment with dex blocked these CRF-mediated effects on AL POMC transcription. In the NIL on p1, CRF induced a 2-fold increase in POMC hnRNA, which (like that in the AL) was inhibited by 30-min pretreatment with dex; in contrast, on p10, dex did not affect the CRF-induced increase in POMC hnRNA. The glucocorticoid receptor subtype responsible for this effect was identified using treatments with specific agonist and antagonists. The type II receptor agonist RU 28362 had an effect similar to that of dex; at both 10(-6) and 10(-8) M, RU 28362 inhibited CRF-induced increases in POMC hnRNA in p1 NIL and p1 and p10 AL.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Databáze: | OpenAIRE |
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