Naloxone Affects the Luteinizing Hormone Secretory Pattern in the Short- and Long-Term Ovariectomized Rat

Abstract

The effect of naloxone, an opiate receptor antagonist, on the secretory pattern of luteinizing hormone (LH) was evaluated in 4-, 16- and 32-week ovariectomized (OVX) rats. Freely moving rats bearing cardiac cannulae were bled every 6 min for 3 h. During the first 90 min of bleeding, an equal volume of saline was injected after withdrawal of each blood sample, while during the second 90 min the replacement was done with saline containing naloxone at a dose of 0.5 (lower dose) or 1.0 (higher dose) mg/kg/h; statistical comparison was done between both treatment periods. In 4-week OVX rats, a significant increase in the mean LH level was observed through the 90-min period of lower-dose naloxone treatment, without significant changes in the pulse frequency and amplitude. In 4-week OVX rats treated with the higher dose and in 16-week OVX rats treated with either the lower or the higher dose, a significant elevation in mean LH levels was observed only during the first 30 min of treatment, which was probably related to the first, large LH peak in the naloxone treatment period. However, together with pulses appearing later in the treatment period, no significant changes were found in the LH pulsatility except for a decrease in frequency in 4-week OVX rats. In 32-week OVX rats, even the lower-dose naloxone did not induce an elevation in mean LH levels. The results demonstrate that naloxone can increase the LH secretion in the absence of ovarian hormones, and further that the effect on LH changes depending upon the dose of naloxone and the time after ovariectomy.

Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretion Is an Inherent Function of GnRH Neurons, as Revealed by the Culture of Medial Olfactory Placode Obtained from Embryonic Rats

“…The interpulse interval of GnRH pulses which occur in GnRH neurons derived from the olfactory placode of rat embryos, approximately 30 min, was very similar to that observed in LH in ovariectomized adult female rats in vivo [19, 25, 26]. The same characteristics of GnRH neurons cultured after being derived from the olfactory placode of embryos were observed in rhesus monkeys [10].…”

“…A GnRH pulse was defined by the method used for detection of the LH pulse [18, 19]. CVs were determined for all the GnRH values that constituted the ascending and descending phases of each potential GnRH pulse.…”

The endogenous feeding suppressant, 2-buten-4-olide, impairs the pulsatile secretion of luteinizing hormone through endogenous opioid peptides

“…Funabashi et al (16) reported that, in ovx rats, intermittent administration of naloxone in the same dose as we used resulted in a significant increase in the mean LH concentration. Kimura et al (17) reported that the same intermittent administration of naloxone in ovx rats significantly increased the frequency and the duration of multiunit activity volleys that accompanied the initiation of each LH pulse.…”

“…Blood samples (0.3 ml) were taken every 6 min for 2 h through the intra-atrial cannula and an equal volume of heparinized saline containing naloxone (Sigma Chemical Co., St Louis, MO, USA) (0.5 mg/kg per h) or heparinized saline only was replaced after each bleeding (16,17). Rats were divided into three experimental groups: group 1, 3V saline þ i.v.…”

Microinjection of LHRH and Its Antagonistic Analog into the Medial Preoptic Area Does Not Affect Pulsatile Secretion of LH in Ovariectomized Rats.

“…Microinjections were performed immediately after the end of the first 90-min control sampling in OVX rats and at 1300 h after control sampling in proestrous rats. The other procedures are the same as reported previously [7] including the analysis of LH pulsatility [11,12].…”