Effects of melatonin in vivo upon luteinizing hormone and prolactin releases induced by opiate receptor antagonists in adult male rats.

The effects of melatonin on LH and PRL releases induced by treatment with naloxone, naloxone methyliodide and nalmefene were studied in adult male rats. Subcutaneous melatonin injection (1.4 mg/Kg) had no effect on LH secretion, but caused an inhibition effect (84%) on LH release induced by naloxone (2.4 mg/Kg). Melatonin too totally inhibited LH secretion induced by naloxone methyliodide (2.8 mg/Kg) and nalmefene (2 mg/Kg) when it was simultaneously administered with each opioid receptor antagonist. Melatonin alone had no significant effect on serum PRL levels, but decreased by 25.5% the inhibitory effect potency of nalmefene on PRL secretion after simultaneous injections. The inhibitory effect potency of naloxone on PRL release increased (16%) when it was administered with melatonin. Simultaneous injection of melatonin with naloxone methyliodide inhibited PRL release (78%) while naloxone methyliodide alone did not modify this secretion. The results obtained with a quaternary opioid antagonist indicate that the opioid receptor type which mediates LH and PRL responses is located respectively outside and inside the blood-brain barrier. Our findings show that opiate antagonists and their quaternary ammonium salts affect secretion of LH and PRL through different mechanisms susceptible to the influence of melatonin.

Stimulatory effect of perhexiline maleate on the basal and LHRH-stimulated luteinizing hormone release from rat pituitary cell aggregates in vitro.

Perhexiline maleate (PM) is an anti-anginal agent of amphiphilic character involved in lipidosis disorders. Experiments were carried out to study PM action on LH release from rat anterior pituitary cell aggregates. PM caused significant and dose-dependent increases of basal LH release when the aggregates had been previously treated with PM for 20 min, then incubated for 30 min with the same concentration of drug after renewal of the culture medium. The increases of basal LH secretion induced by PM were 69% (p < 0.001) at a concentration of 10(-7)M, 130% (p < 0.001) at a concentration of 10(-5)M and 250% (p < 0.001) at a concentration of 10(-4)M. PM also increased the LHRH-stimulated LH release by 25.5% (p < 0.05) at a concentration of 10(-5)M and by 74.5% (p < 0.01) at the concentration of 10(-4)M. The results showed that PM was more potent on basal LH release than on LH stimulated by LHRH. The mechanism of this action remains unclear. It may be due to the lipidosis property of the drug.

Effect of naloxone and beta-casomorphin on the hypothalamic-pituitary-luteinizing hormone axis in vitro.

The effect of naloxone and beta-casomorphin on luteinizing hormone (LH) release from pituitary cell aggregates, obtained by three-dimensional culture, with or without mediobasal hypothalamic fragments was studied in vitro. Short-term naloxone perifusion at a concentration of 10(-5)M did not modify either basal or LHRH-stimulated LH release from the pituitary cell aggregates. In contrast, a 12-min naloxone perifusion at the same concentration caused an increase in LH release in the mediobasal hypothalamic-pituitary cell aggregate axis. This increase was rapid (12-16 min after time pulse), marked [up to 10 times (p less than 0.004) the initial base line], short (return to the base line secretion 32-40 min after the beginning of the time pulse) and dose-dependent, with a rise greater than 1000% at a concentration of 10(-4) (p less than 0.006). The same effect was observed when a second pulse was applied 48 min after the first one. LH release induced by naloxone was antagonized 56 +/- 2% (p less than 0.03) by beta-casomorphin (an exogenous opiate) at a concentration of 10(-5) M. beta-casomorphin alone did not modify LH basal secretion, but inhibited 25.1 +/- 2.4% (p less than 0.008) LH release enhanced by LHRH. These results indicate that naloxone, an opiate antagonist, markedly increases LH release via a mu-type opioid receptor mechanism at the hypothalamic level only, during short-term exposure.

[Biological effects in the female rat of active mixed immunization against estradiol and testosterone]. / Effets biologiques chez la ratte de l'immunisation active mixte contre l'estradiol et la testostérone.

Active simultaneous immunization of female rats against 17 beta-estradiol and testosterone induced formation of ovarian haemorrhagic and cystic follicles. A 2-fold increase in serum luteinizing hormone but any differences in prolactin levels were noted.

[In vitro effect of 5 alpha-androstane-3 beta, 17 beta diol on the liberation of follicle stimulating hormone (FSH) induced by LH-RH]. / Influence in vitro du 5 alpha-androstane-3 beta, 17 beta diol sur la libération de l'hormone folliculostimulante (FSH) induite par LH-RH.

A continuous flow incubation (perifusion) was used to examine the effect of 5 alpha-androstane-3 beta, 17 beta diol 3 beta diol) on the release of FSH induced by LH-RH. Over a 3 h-period the 3 beta diol exerts inhibitory effects on male and female pituitaries at high dose (1 microgram/ml) and only on male pituitaries at low dose (100 ng/ml).

[Effects of 5 alpha-androstane-3 beta, 17 beta-diol on release of luteinizing hormone (LH) from 36-38 day old male and female rat anterior pituitaries perifused with constant amounts of gonadotrophin releasing hormone (Gn-GH)]. / Etude, par la technique de périfusion d'hypophyse antérieure, de l'influence du 5 alpha-androstane-3 beta, 17 beta diol sur la libération, stimulée en continu par la gonadolibérine (Gn-RH), de l'hormone lutéinisante (LH) chez le rat mâle et le rat femelle, âgés de 36-38 jours.

In vitro (perifusion of rat pituitaries) the 5 alpha-androstane-3 beta, 17 beta diol (3 beta diol) exerts inhibitory effects on Gn-RH stimulated LH secretion. The 3 beta diol is more potent at high dose (1 micrograms/ml) than low dose (100 ng/ml) and in the male rat than in the female rat.