SYSTEMIC CHALLENGE WITH ENDOTOXIN STIMULATES CORTICOTROPIN-RELEASING HORMONE AND ARGININE-VASOPRESSIN SECRETION INTO HYPOPHYSEAL PORTAL BLOOD - COINCIDENCE WITH GONADOTROPIN-RELEASING-HORMONE SUPPRESSION

We tested the hypothesis that systemic immune/inflammatory challenge ( endotoxin) activates the neuroendocrine stress axis centrally by stimu lating the secretion of CRH and arginine vasopressin (AVP) into hypoph yseal portal blood. In addition, we examined the temporal association between this stimulation of the stress neuropeptides and the inhibitio n of pulsatile GnRH and LH secretion. Using alert, normally behaving e wes, hypophyseal portal and peripheral blood were sampled simultaneous ly at 10-min intervals for 14 h. Temperature was monitored remotely by telemetry at the same interval. Endotoxin (400 ng/kg, iv bolus) or sa line as a control was injected after a 4-h baseline period. Portal blo od was assayed for CRH, AVP, and GnRH, and peripheral blood was assaye d for cortisol, progesterone, and LH. In controls, hypophyseal portal CRH and AVP remained just above or at assay sensitivity, and cortisol showed a regular rhythmic pattern unaffected by saline and typical of basal secretion. In contrast, endotoxin potently stimulated CRH and AV P secretion into portal blood, and cortisol and progesterone into peri pheral blood. Both CRH and AVP generally rose and fell simultaneously, although the peak of the AVP response was approximately 10-fold great er than that of CRH. The AVP in portal blood was not due to recirculat ion of hormone secreted into the peripheral circulation by the posteri or pituitary gland, because the AVP increase in peripheral blood was n egligible relative to the marked increase in portal blood. The stimula tion of CRH and AVP coincided with significant suppression of GnRH and LH pulsatile secretion in these same ewes and with the generation of fever. We conclude that endotoxin induces central activation of the ne uroendocrine stress axis, stimulating both CRH and AVP release into th e hypophyseal portal blood of conscious, normally behaving ewes. This response is temporally coupled to inhibition of pulsatile GnRH and LH release as well as with stimulation of adrenal cortisol and progestero ne secretion and generation of fever.