Submission Number: NAT-4-20-10

Abstract Number: 550

CORTISOL DOES NOT MEDIATE ENDOTOXIN-INDUCED INHIBITION OF PULSATILE LH SECRETION.

N Briard ¹, GK Barrell ², Heather J Billings* ¹, KM Breen* ¹, M Brown ¹, EA Young ¹ and Fred J Karsch* ¹

Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, USA. ¹
Animal and Food Sciences Division, Lincoln University, New Zealand. ²

Abstract:
In ovariectomized ewes, endotoxin inhibits pulsatile GnRH and LH secretion and concurrently stimulates hormones of the neuroendocrine stress axis - AVP, CRH, ACTH, cortisol and progesterone (Battaglia et al., Endocrinology 1998, 139:4175). Each of these stress axis hormones is a potential mediator of the endotoxin-induced inhibition of GnRH and LH pulses. Here we tested the hypothesis that cortisol mediates this inhibition of pulsatile LH secretion. Our approach was to test if the cortisol synthesis inhibitor, metyrapone, could reverse the inhibitory effect of endotoxin on LH pulses in ovariectomized ewes. Two doses of endotoxin (400 or 40 ng/kg, i.v.) were used because the high dose inhibits at both the hypothalamic and pituitary levels whereas the low dose appears to inhibit LH pulses by acting primarily at the pituitary gland. Jugular blood was collected at 10 or 6-min intervals during a 12-h period to measure LH, cortisol and progesterone; core body temperature was monitored to confirm endotoxin efficacy. Endotoxin was injected at hour 6 and metyrapone (11.3 mg/kg, i.m.) was injected hourly from 3h before to 3h after endotoxin. Control ewes received endotoxin and metyrapone vehicle (6 ewes/group). All ewes developed a fever; metyrapone did not affect this response. Metyrapone blocked the endotoxin-induced stimulation of cortisol secretion; plasma concentrations remained near the pretreatment level. Both doses of endotoxin profoundly inhibited pulsatile LH secretion (p<0.05). This was not reversed when the cortisol response was blocked by metyrapone. Metyrapone enhanced endotoxin-stimulated progesterone secretion, but preliminary evidence suggests the progesterone levels achieved were not sufficient to produce LH pulse suppression. We conclude that cortisol does not mediate endotoxin-induced LH inhibition, especially at the pituitary level, which appears to be the primary site influenced by the low dose of endotoxin. Ongoing experiments are testing if this holds true for the hypothalamic effect of endotoxin. (Supported by NIH HD-30773 and FRM SE000738-01).

Keywords: Endotoxin, LH, Cortisol, Sheep

This abstract is being presented at: 8:00 AM in session:
Neuroendocrinology II