Regulation of vasopressin V1b receptors and stress adaptation.
Vasopressin (VP) regulates pituitary corticotroph function by acting upon plasma membrane G-protein receptors of the V1b subtype (V1bR), coupled to calcium-phospholipid signaling. The number of these receptors in the anterior pituitary varies during stress in direct correlation with corticotroph responsiveness, suggesting that the V1bR plays an important role during adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress. The molecular regulation of pituitary V1bR involves transcriptional and translational mechanisms. V1bR gene transcription, which is necessary to maintain V1bR mRNA levels, depends on a number of responsive elements in the promoter region, of which the stretch of GA repeats near the transcription start point (GAGA box) is essential. Although transcriptional activation is necessary to maintain V1bR mRNA levels, the lack of correlation between VP binding and V1bR mRNA suggests that V1bR content is mainly regulated at the translational level. Two potential mechanisms by which the 5' untranslated region (5'UTR) of the V1bR mediates negative and positive regulation of V1bR translation were identified. This includes the repressor effect of small open reading frames (ORF) present upstream of the main V1bR ORF, and an internal ribosome entry site (IRES), which activates V1bR translation. 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.
Volpi
Simona
S
Section on Endocrine Physiology, Developmental Endocrinology Branch, NICHD, NIH, Bldg. 10, Rm. 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862, USA.
Rabadán-Diehl
Cristina
C
Aguilera
Greti
G
D000222:Adaptation, Physiological; D000818:Animals; D005786:Gene Expression Regulation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017483:Receptors, Vasopressin