Pituitary-specific expression and glucocorticoid regulation of a proopiomelanocortin fusion gene in transgenic mice.

AUTOR(ES)

Tremblay, Y

RESUMO

The product of a single gene encoding proopiomelanocortin (POMC) is differentially processed to produce corticotropin and alpha-melanotropin in anterior and intermediate pituitary cells, respectively. Hormonal control of POMC gene transcription and of corticotropin or alpha-melanotropin release is also tissue-specific; for example, glucocorticoids specifically inhibit anterior but not intermediate pituitary POMC transcription. Outside the pituitary gland, very low levels of POMC mRNAs are present in brain, testes, ovaries, and placenta. We have used transgenic mice to identify POMC 5' flanking sequences that are sufficient for tissue-specific expression and glucocorticoid regulation in anterior and intermediate pituitary cells. Three lines of transgenic mice were established, each carrying 50-75 copies (per cell) of a chimeric rPOMCneo gene constituted of rat POMC promoter sequences and of bacterial neomycin-resistance coding sequence. High levels of rPOMCneo transcripts were detected in pituitaries of mice from all three lineages. In situ hybridization revealed that the ratio of intermediate to anterior pituitary transcripts was similar for the transgene and endogenous POMC mRNA. rPOMCneo transcripts were not detected in any other tissue except at very low levels in the testes in two transgenic lines. Endogenous mouse POMC mRNA increased in response to depletion of plasma glucocorticoids (adrenalectomy) and decreased after glucocorticoid treatment; rPOMCneo transcripts were altered to the same extent by these treatments in all three lines. Intermediate pituitary and testicular rPOMCneo transgene expression was not altered by these treatments. Thus, no more than 769 base pairs of the rat POMC promoter are required for pituitary-specific expression and for specific glucocorticoid inhibition of the POMC gene in the anterior pituitary.

Documentos Relacionados

• Regulatory elements controlling pituitary-specific expression of the human prolactin gene.
• Identification of DNA elements cooperatively activating proopiomelanocortin gene expression in the pituitary glands of transgenic mice.
• Interaction of Ets-1 and the POU-homeodomain protein GHF-1/Pit-1 reconstitutes pituitary-specific gene expression.
• Hormonal regulation of the thyrotropin beta-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1.
• Tissue-specific expression and methylation of a thyroglobulin-chloramphenicol acetyltransferase fusion gene in transgenic mice.