Transcriptional and post-transcriptional mechanisms regulating the rat pituitary vasopressin V1b receptor gene.
The number of V1b vasopressin receptors (V1bR) in the anterior pituitary plays an important role during adaptation of the hypothalamic-pituitary-adrenal axis to stress in rats. Regulation of V1bR expression involves transcriptional and translational mechanisms. One of the elements mediating transcriptional activation of the rat V1bR gene is a long stretch of GAGA repeats (GAGA box) in the promoter located near the transcription start point capable of binding a protein complex of 127 kDa present in pituitary nuclear extracts. There is a lack of correlation between changes in V1bR mRNA and the number of VP binding sites, suggesting that V1bR expression depends on the efficiency of V1b R mRNA translation into protein. Two mechanisms by which the 5' untranslated region (5'-UTR) of the rat V1bR mRNA can mediate either inhibition or activation of V1bR mRNA translation have been identified. First, upstream open reading frames (ORF) present in the 5'-UTR repress translation of the major ORF encoding the V1b receptor, and secondly, an internal ribosome entry site (IRES) activates V1bR translation. Stimulation of IRES activity through protein kinase C-mediated pathways results in V1bR mRNA translation increasing V1bR protein levels. The existence of multiple loci of regulation for the V1bR at transcriptional and translational levels provides a mechanism to facilitate plasticity of regulation of the number of pituitary vasopressin receptors according to physiological demand.
Aguilera
G
G
Developmental Endocrinology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Greti_Aguilera@nih.gov
Volpi
S
S
Rabadan-Diehl
C
C
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014667:Vasopressins / Q000378:metabolism
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014667:Vasopressins