A Significant Participation of Leukemia Inhibitory Factor in Regulating the Reproductive Function in Rats: A Novel Action of the Pleiotropic Cytokine

Abstract

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine exhibiting diverse biological activities in various tissues and cell types. Accumulating evidence suggests a crucial role for LIF in regulating the hypothalamo-pituitary–adrenal axis, but information is limited regarding whether the cytokine also exerts a significant influence on other endocrine systems. In this study, we examined a possible involvement of LIF in the generation of ovarian steroid-induced luteinizing hormone (LH) and prolactin (PRL) surges in the rat. Experiments were performed on both normally fed and 3-day-fasted rats, which were ovariectomized and primed with estradiol and progesterone. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. All the following substances were given intracerebroventricularly at 11:00 h. Compared to control serum, undiluted and 5-times diluted preparations of anti-rat LIF serum caused a partial but significant suppression of LH surge to a similar extent. The two different concentrations of antibody also delayed the onset of PRL surge to a comparable degree. Fasted rats were devoid of significant surges of the hormones, while 1.0 and 3.0 nmol, but not 0.3 nmol, of recombinant murine LIF given to these animals led to a partial but significant recovery of both LH and PRL surges. This stimulatory potency of LIF on both hormones was already maximal at its 1.0-nmol dose. These results demonstrate for the first time a significant participation of LIF in the generation of LH and PRL surges in the rat. A novel action of the pleiotropic cytokine is reported herein.