Hypothalamic pituitary adrenal axis and hypothalamic-neurohypophyseal responsiveness in water-deprived rats

The differential effects of osmotic stimulation on magnocellular and parvoc ellular hypothalamic neurons were studied by analysis of corticotropin-rele asing hormone (CRH) and vasopressin (VP) expression in controls and 48-h wa ter-deprived rats subjected to either restraint for 1 h or a single lipopol ysaccharide injection (250 mug/100 g). Water deprivation reduced basal CRH mRNA levels but the increments following 4 h of restraint or 6 h lipopolysa ccharide (LPS) injection were similar to those in controls. In contrast, wa ter deprivation had no effect on basal VP heteronuclear RNA (hnRNA) and mRN A levels in parvocellular neurons, but responses to restraint or LPS inject ion were reduced. VP expression in magnocellular paraventricular and suprao ptic nuclei, and plasma sodium and vasopressin were higher in water-deprive d rats, changes which were unaffected by restraint. LPS injection reduced V P mRNA but not hnRNA levels in magnocellular neurons and increased plasma v asopressin levels only in water-deprived rats independently of changes in p lasma sodium. This was accompanied by an increase in vasopressin mRNA conte nt in the posterior pituitary. The data show that the blunted ACTH response s to acute stress during chronic osmotic stimulation are correlated with th e inability of parvocellular neurons to increase VP rather than CRH express ion. In addition, LPS-induced endotoxemia causes disturbances of the magnoc ellular vasopressinergic system with an unexpected potentiation of osmotic simulated VP secretion. The lack of increase in VP transcription after LPS and changes in VP mRNA distribution suggest that endotoxemia affect the sec retory process at the levels of the neurohypophyseal axon terminal. (C) 200 1 Academic Press.