Maintenance of Gonadotropin Secretion by Glucocorticoids under Stress Conditions through the Inhibition of Prostaglandin Synthesis in the Brain

Abstract

We have previously reported that glucocorticoids counteract the suppressive effects of tumor necrosis factor-alpha on both pulsatile and surge secretion of LH. This suggests that glucocorticoids have a protective effect on reproductive function under infectious stress. In the present study, we examined whether glucocorticoids maintain pulsatile LH secretion under various conditions of acute stress and the possible involvement of prostaglandins (PGs) in glucocorticoid actions. Three different types of stressors, namely infectious (lipopolysaccharide, 0.5 microg/kg), hypoglycemic (2-deoxy-D-glucose, 100 mg/kg), and restraint stress (1 h) were applied to ovariectomized rats. In ovariectomized rats, LH pulses were partially suppressed by restraint, but not by lipopolysaccharide or 2-deoxy-D-glucose. On the other hand, adrenalectomy (ADX) significantly enhanced the suppressive effects of all the stressors applied on LH pulses. Treatment with both corticosterone (25 mg/kg) and indomethacin (10 mg/kg) in ADX rats significantly attenuated the suppressive effects of these stressors on LH pulses. In addition, the immunoreactivity of cyclooxygenase-2, a PG-synthesizing enzyme, in the brain under stress conditions was much enhanced by ADX, and this was counteracted by corticosterone treatment. Similarly, an increase in body temperature under restraint stress was enhanced by ADX and suppressed by corticosterone. These results suggest that suppression of LH pulsatility by stress is mediated by PGs in the brain, and that increased release of endogenous glucocorticoids in response to stress counteracts this suppression by inhibiting PG synthesis, and thereby maintains reproductive function regardless of the nature of the stressor.

The Impact of Stress on Reproduction: Are Glucocorticoids Inhibitory or Protective to Gonadotropin Secretion?

“…An article by Matsuwaki et al (1), appearing in this issue of Endocrinology, opposes the notion that glucocorticoids play an inhibitory role on the reproductive axis, specifically during stress. This research group led by Masugi Nishihara from the University of Tokyo claims that glucocorticoids are protective rather than inhibitory to gonadotropin secretion during stress, through a specific mechanism that involves prostaglandin (PG) synthesis in the brain (Fig.…”

Childhood Abuse and Age at Menarche

“…Severe stress in early life is associated with suppression of the HPG axis. 32, 33 However, animal research suggests that under conditions of stress, the HPA axis may release endogenous glucocorticoids that prevent stress-induced suppression of the HPG axis. 32, 33 …”

Gonadotropin-Inhibitory Hormone Plays Roles in Stress-Induced Reproductive Dysfunction

“…Physical and psychological stressors suppress HPG activity through inhibition of gonadotropin-releasing hormone (GnRH) in both males and females (5–7), thereby decreasing luteinizing hormone (LH) and follicle-stimulating hormone release from the pituitary (8, 9). When the relationships between stress and reproductive functions are evaluated experimentally, inflammatory stress induced by a Gram-negative bacterial cell wall component, lipopolysaccharide (LPS), and psychological stress induced by restraint stress are frequently used.…”