Interleukin-1 stimulates luteinizing hormone release during the midfollicular phase in the rhesus monkey: a novel way in which stress may influence the menstrual cycle.

Abstract

We previously demonstrated an inhibitory effect of an inflammatory/immune-like stress challenge, as simulated by intracerebroventricular interleukin-1 alpha (IL-1 alpha) administration, on LH secretion in the ovariectomized rhesus monkey. This was shown to be the result of activation of the hypothalamo-pituitary-adrenal axis by the cytokine. In the present experiments, we have investigated LH and cortisol responses to IL-1 alpha administration in intact monkeys during the follicular phase of the menstrual cycle. Eleven adult rhesus monkeys, bearing an intraventricular cannula for cytokine administration, were used. Cycle parameters were monitored in the preceding control cycles, during the experimental cycles, as well as in subsequent cycles by daily measurements of estradiol and progesterone concentrations and daily menstruation checks. The experiments were performed according to estradiol concentrations: estradiol, 5-38 pg/mL, group 1, early follicular; and estradiol, 50-64 pg/mL, group 2, midfollicular. The effects of intracerebroventricular saline (30 microL/30 min) or IL-1 alpha (4.2 micrograms/30 min) infusions on LH, FSH, and cortisol were compared. After saline infusion, there was no significant change in LH secretion. No significant acute change in LH occurred after IL-1 alpha administration in group 1 (to 0.98 +/- 0.12 ng/mL by 5 h from a baseline of 0.85 +/- 0.12); however, the length of the follicular phase was significantly prolonged in these early follicular phase animals. IL-1 significantly increased LH release in monkeys during the midfollicular phase (group 2; to 2.45 +/- 0.45 ng/mL by 5 h from a baseline of 0.88 +/- 0.11; P < 0.05 vs. baseline and all other groups). FSH was also increased in the latter group. When the experimental observation period was extended to 18 h after IL or saline treatment in eight monkeys, LH and FSH consistently increased after IL administration in three of four animals (to 4.3 +/- 0.7 ng/mL), and in one animal, a surge-like gonadotropin release occurred, whereas no further changes occurred after saline. IL-1 alpha, but not saline, significantly increased cortisol and progesterone release. In conclusion, our results demonstrate that dependent on estradiol concentrations, an acute inflammatory/immune-like stress challenge can affect the hypothalamo-pituitary-ovarian axis differently, either by stimulating gonadotropin release in the presence of significant estradiol concentrations or by inhibiting follicular maturation when given in the presence of low estradiol levels.