othalamic VP secretion. These studies revealed marked and sustained decreases in VP V2 receptors and aquaporin 2 in kidney medulla following LPS induced endotoxemia, and that these alterations lead to impaired capacity to concentrate urine. Transcriptional and post-transcriptional mechanisms regulating the number of CRH and VP receptors in the pituitary play an important role in the control of HPA axis activity. An essential element regulating V1b receptor transcription is a GAGA box located in the proximal promoter, which binds a protein complex found in pituitary nuclear extracts. Stress causes transient increases in GAGA binding activity an effect possible mediated by VP. Experiments using the hypothalamic cell line, H32, which expresses endogenous VP receptors showed that VP caused a rapid increase in GAGA binding activity followed by a decline. This effect of VP paralleled changes in ERK phosphorylation and it was mimicked by epidermal growth factor (EGF) and blocked by inhibitors of the EGF receptor and MAPK pathway. While the early increase was blocked by intracellular calcium chelators, the declining phase was prevented by protein kinase C inhibition. Studies using receptor subtype specific analogs or different cell lines transfected with either V1a or V1b receptors showed that the pathways involved in transactivation of the MAPK pathway by VP are cell specific and independent of the V1 receptor subtype. This data suggest that VP released into the pituitary portal circulation during stress activates V1b receptor transcription through transactivation of the EGF receptor. At the translational level, studies showed that the 5 prime untranslated region (5?UTR) of the V1b receptor mRNA contains elements, which can inhibit or stimulate translation. While the presence of upstream open reading frames in the 5 prime untranslated region play a role maintaining low translational activity in basal conditions, an internal ribosome entry site (IRES) can initiate translation independently of cap. Stress conditions which