Kappa‐Opioid Receptor Involvement in the Regulation of Pulsatile Luteinizing Hormone Release During Early Pregnancy in the Rat

Abstract

The object of this study was to gain further insight into endogenous opioid peptide suppression of pulsatile luteinizing hormone (LH) release in early gestation in the rat by examining whether selective blockade of mu-, delta-, or kappa-opioid receptor(s) results in stimulation of pulsatile LH secretion at this time. Previous reports demonstrated stimulation of pulsatile LH release during early gestation by intravenous infusions of naloxone, an endogenous opioid peptide receptor antagonist whose binding is not specific to a single class of opioid peptide receptors. In the present study, naloxone infused intraventricularly similarly stimulated an increase in pulsatile LH release on Days 7 to 8 of gestation. Antagonists of specific opioid peptide receptor subtypes were thus given by this route. Administration of nor-binaltorphimine, an antagonist of kappa-opioid receptors, but not P-funaltrexamine or ICI 174, 864, antagonists of mu-and delta-opioid receptors, respectively, exerted a stimulatory action on both LH pulse amplitude and frequency similar to that of naloxone, indicating involvement of this opioid peptide receptor subtype in the endogenous opioid peptide suppression of pulsatile LH release in early gestation in the rat.Luteinizing hormone (LH) release is pulsatile during early pregnancy in the rat (1-3). The secretion of this hormone is important for maintenance of the corpus luteum, and therefore pregnancy, on Days 7 to 8 of gestation (4-10). Administration of naloxone, an endogenous opioid peptide (EOP) receptor antagonist, incieases LH pulse amplitude and frequency at this stage of pregnancy (2, 3), and this stimulatory effect is not exerted at the pituitary level (2). This latter study demonstrated that EOPs exert a suppressive action on pulsatile LH release during early pregniincy in the rat. However, the binding of naloxone is not specific to one class (i.e. mu, delta or kappa) of opioid peptide receptors (1 1-13). Thus, the objective of this study was to gain further imight into EOP regulation of LH pulse amplitude and frequency in early gestation, by examining whether selective blockade of mu-, delta-or kappa-opioid receptor(s) results in stimulation of pulsatile LH release at this time. Results E.lperiment IBasal pulsatile LH release in rats receiving a 4-h intraventricular infusion of artificial cerebrospinal fluid (CSF) was similar to that previously observed in early gestation in rats receiving a prolonged iv infusion of saline ( Fig. 1; 2, 3). In addition, naloxone given intraventricularly stimulated all three parameters of pulsatile LH secretion (Fig. 1) in a manner similar to that previously observed in response to iv naloxone infusion (2, 3). Thus, blockade of central EOP receptors can be elicited by intraventricular administration of naloxone. Moreover, these data demonstrate that implantation of cannulae in the third ventricle, together with brief ether exposure and intraventricular infusion on the day of the experiment, have no untoward effect on either basal or naloxone-stimul...

The Role of Neurokinin B Signalling in Reproductive Neuroendocrinology

“…Dyn has long been known to decrease GnRH pulse frequency [34], and its primary role as such has been postulated to be in mediating the negative feedback effects of progesterone (P 4 ) on the neuroendocrine hypothalamus [35]. The κ-opioid receptor (KOR), through which Dyn preferentially signals [36], is not abundantly expressed in the vicinity of GnRH neurones [37,38].…”

Role of Neurokinin B and Dynorphin A in pituitary gonadotroph and somatolactotroph cell lines

“…MUA volleys in kisspeptin/metastin neurons are inhibited by Dyn, which results in a decrease in gonadotropin release [41,42]. We expected Dyn to exert inhibitory effects on pituitary gonadotrophs and lactotrophs because these cells, like kisspeptin/metastin neurons, express the Dyn receptor, KOR.…”

Dynorphin-Kappa Opioid Receptor Signaling Partly Mediates Estrogen Negative Feedback Effect on LH Pulses in Female Rats

“…Dynorphin-KOR signaling is considered to be involved in the suppression of GnRH/LH pulses, because central administration of nor-binaltorphimine (nor-BNI), a selective KOR antagonist, increases the amplitude and frequency of LH pulses during early pregnancy [23] and the mean LH level and LH pulse frequency during midpregnancy [24] in rats. Further, Goodman et al [25] suggested that the central Dyn-KOR system mediates progesterone negative feedback on GnRH/LH pulses in ewes.…”