Loss of Estradiol-Positive Feedback Action on LH Release during Prepubertal Period in Rats Treated Postnatally with an Opiate Antagonist

Abstract

The purpose of this study was to determine the role of endogenous opioid peptides in the differentiation of the neuroendocrine brain that leads to estradiol-dependent LH release in female but not in male rats. Newborn intact or gonadectomized rats were given an opiate antagonist, naltrexone, with or without an opiate agonist, morphine, or saline alone during the critical period of the sexual differentiation of the brain (days 1–10). These animals were weaned on day 21 and injected with estradiol benzoate (EB) in oil or oil alone twice, 48 h apart, and the action of EB on plasma and pituitary levels of LH was studied. The release of LH during the prepubertal period was increased following EB treatment both in intact females and gonadectomized males and females, but not in intact male rats. Naltrexone treatment during the neonatal period prevented the EB-induced LH release in both intact and gonadectomized rats. Morphine blocked the inhibitory effect of naltrexone on LH release. Naltrexone treatment did not directly affect pituitary LH storage, but prevented EB-induced depletion of pituitary LH pools; morphine blocked this action of naltrexone. Hence, the inhibitory effect of naltrexone on LH release appeared to result from an alteration of the central mechanism responsible for EB-induced LH secretion. These results suggest a possible involvement of endogenous opioid peptides in the neuroendocrine brain differentiation that results in LH release after EB treatment during the prepubertal period in rats.

Effects of treatment with the opioid antagonists naloxone and naltrexone on LH secretion and on sexual maturation in immature female rats

“…Thus the endogenously evoked oestradiolpositive feedback on LH release seemed to be effectively present in both naltrexone-treated and in saline-treated 31-day-old rats. Lira et al (1986) reported the absence of this oestradiol-positive feedback on day 24 in neonatally naltrexone-treated Sprague-Dawley rats. Although the central mechanism for oestradiol-positive feedback might have been restored or developed between days 24 and 31 in our rats, it seems likely that the difference in rat strain may also play a role.…”

“…A clear advancement of the onset of puberty in the female rat after neonatal administration of naloxone was reported by Sirinathsinghji, Motta & Martini (1985), whereas Lira, Phipps & Sarkar (1986) reported impairment of the development of the oestradiolpositive feedback action on LH release during prepuberty after neonatal administration of another opioid antagonist, naltrexone. The results of Lira et al (1986) suggest that naltrexone has a delaying effect on the onset of puberty in the female.…”

“…The results of Lira et al (1986) suggest that naltrexone has a delaying effect on the onset of puberty in the female. As a possible explanation for this discrepancy in results obtained with the opioid receptor antagonists naloxone and naltrexone, Lira et al (1986) have suggested the duration of the blockade of the opioid receptors (naloxone being the short-lasting opioid antagonist).…”

The control of sexual differentiation of the reproductive system and brain

“…Control of sexual differentiation Lira et al 1986, Romano et al 1990) and induces feminization in males (Sandberg et al 1990, Johnston et al 1992. Reznikov et al (2005) have also suggested that endogenous opiates are the mediators of the feminizing effect induced by stress.…”