PARENT SESSION
SLIDE SESSION 4: NEUROENDOCRINOLOGY
Chairs: Donal Skinner, Fred Karsch, Heather Billings (Trainee)
Univ Ottawa-Arts Hall 257
2:30 PM-4:30 PM
29
DO PROSTAGLANDINS MEDIATE THE DISRUPTIVE EFFECT OF ENDOTOXIN ON THE ESTRADIOL-INDUCED LH SURGE?
Breen, Kellie1,2, Billings, Heather1, Briard, Nathalie 1, Karsch, Fred1,2, 1 2
ABSTRACT- Prostaglandins (PGs) mediate many pathophysiologic responses to endotoxin including fever, neuroendocrine stress axis activation and suppression of pulsatile GnRH and LH secretion in the ovariectomized ewe (Endocrinology 141: 1050, 2000). Endotoxin also inhibits the estradiol-induced LH surge. Here, we tested the hypothesis that PGs mediate the suppressive effect of endotoxin on the LH surge. Ovariectomized sheep were treated with a PG synthesis inhibitor, flurbiprofen (FB), in conjunction with an endotoxin treatment known to disrupt the LH surge. Artificial estrous cycles were created by sequential treatments with progesterone and estradiol implants. Luteolysis was simulated by removal of progesterone; 16 h later estradiol implants were inserted to establish a preovulatory-like estradiol rise. Separate experiments were run over two successive breeding seasons. In the first, 6 ewes each received three treatments: 1) estradiol plus vehicle, 2) estradiol plus endotoxin, and 3) estradiol plus endotoxin and FB. Endotoxin (400 ng/kg, iv) and FB (2 mg/kg, iv) were administered just before estradiol and FB was again administered 5 h later. Jugular blood was sampled at 1-2 h intervals to identify the LH surge. Endotoxin suppressed (p<0.05) the estradiol-induced LH surge (assessed as integrated surge LH released); FB did not reverse this suppression. Nevertheless, FB blocked endotoxin-induced fever, which is a PG-dependent response. In the second breeding season, we confirmed this finding on the LH surge and, in addition, tested whether PG synthesis is essential for endotoxin to suppress tonic LH secretion in ovariectomized ewes treated with low luteal phase levels of estradiol. Endotoxin markedly inhibited (p<0.001) tonic LH secretion, assessed in blood sampled every 30 min. FB fully reversed this inhibition. Our findings confirm that PG synthesis is required for endotoxin to suppress tonic LH secretion. In marked contrast, PGs do not appear to be obligatory components of the pathway whereby endotoxin suppresses the estradiol-induced LH surge. Supported by NIH-HD-30773.
KEY WORDS: luteinizing hormone surge, tonic luteinizing hormone, prostaglandin