ENDOTOXIN INHIBITS THE REPRODUCTIVE NEUROENDOCRINE AXIS WHILE STIMULATING ADRENAL-STEROIDS - A SIMULTANEOUS VIEW FROM HYPOPHYSEAL PORTAL AND PERIPHERAL-BLOOD

This study was designed to test the hypothesis that systemic immune ch allenge with endotoxin inhibits the reproductive axis centrally by sup pressing GnRH pulsatile release into hypophyseal portal blood. Using a lert, normally behaving, ovariectomized ewes, we sampled hypophyseal p ortal blood at 10-min intervals beginning 4 h before and continuing 10 h after endotoxin (400 ng/kg, iv bolus, n = 6) or saline (vehicle, iv , n = 6). Simultaneous jugular samples for measurement of LH, cortisol , and progesterone were taken, and core body temperature was monitored by telemetry. Saline had no effect on any of the parameters in contro l ewes. In contrast, endotoxin dramatically inhibited the reproductive neuroendocrine axis coincident with stimulating the adrenal steroids, cortisol and progesterone, and elevating body temperature. Mean GnRH collection rate and GnRH pulse amplitude were suppressed (pre-vs. 7 h postendotoxin: collection rate 0.93 +/- 0.31 us. 0.34 +/- 0.13 pg/min; amplitude 4.13 +/- 1.33 vs. 1.30 +/- 0.41 pg/min per pulse; P < 0.05 and P = 0.01). However, endotoxin did not have a significant effect on GnRH pulse frequency. Along with inhibited GnRH secretion, endotoxin significantly suppressed mean LH concentrations (P = 0.001) and LH pul se amplitude (P < 0.05). In addition, endotoxin suppressed LH pulse fr equency (P = 0.01). Coincident with reproductive inhibition, endotoxin stimulated cortisol (P < 0.001), progesterone (P < 0.01), and core bo dy temperature (P < 0.001). We conclude that the suppressive effects o f endotoxin on the reproductive axis can be mediated centrally through an inhibition of GnRH and thus LH pulsatile secretion. The coincident stimulation of cortisol, progesterone, and temperature raises the pos sibility that the central inhibition of the reproductive system may be a consequence of any or all of these activated parameters.