D.A. Van Vugt

Effects of naloxone, morphine and methionine enkephalin on serum prolactin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone

Abstract The response of 5 anterior pituitary hormones to single injections of naloxone, morphine and metenkephalin administration was measured in male rats. Morphine and met-enkephalin significantly increased serum prolactin and GH concentrations, and significantly decreased serum LH and TSH concentrations. Naloxone reduced serum prolactin and GH concentrations, increased serum LH and FSH, but had little effect on serum TSH concentrations. Concurrent injections of naloxone with morphine or met-enkephalin reduced the response to each of the drugs given separtely. These results suggest that endogenous morphinomimetic substances may participate in regulating secretion of anterior pituitary hormones.

Naloxone inhibition of stress-induced increase in prolactin secretion.

Abstract Naloxone, an opiate antagonist that acts by binding to opiate receptors in the brain, was given to rats stressed by immobilization or heat in an attempt to inhibit stress-induced release of prolactin. Both stresses resulted in approximately a 5-fold increase in serum prolactin concentration. Naloxone, at a dose of 0.2 mg/kg b.w. completely or partially inhibited the stress-induced rises in serum prolactin, and reduced serum prolactin concentrations in unstressed rats to below control values. It is concluded that endorphins may be responsible for increased release of PRL during stressful conditions.

Interaction between opiates and hypothalamic dopamine on prolactin release.

Abstract Opiate stimulation of prolactin (PRL) release appears to involve a hypothalamic mechanism(s). The present study utilized both central acting drugs and direct measurement of hypothalamic dopamine (DA) to investigate this problem. Administration of L-dopa, the precursor of DA; piribedil, a DA agonist; or amineptine, a DA reuptake inhibitor, each decreased serum PRL concentrations. Morphine sulfate (MS) and haloperidol (HAL) significantly increased serum PRL levels. L-dopa and piribedil reversed the stimulatory effect of MS on serum PRL concentrations by increasing dopamine activity. MS blocked the inhibitory effects of amineptine on serum PRL release, possibly by decreasing the concentration of DA available for reuptake. Injection of subeffective doses of HAL concurrently with a subeffective dose of MS increased serum PRL concentrations, by an additive inhibitory action on dopaminergic activity. β-endorphin, an endogenous opioid peptide, decreased the rate of DA turnover in the median eminence, and increased serum PRL levels approximately 10 - fold. These observations indicate that opiates stimulate PRL release by decreasing DA activity in the median eminence.

Counteraction of gonadal steroid inhibition of luteinizing hormone release by naloxone.

The effect of naloxone on the negative feedback action of gonadal steroids on luteinizing hormone (LH) release was studied in castrated male and female rats. The reduction by estradiol benzoate or testosterone propionate of elevated serum LH levels in rats ovariectomized for 4 weeks was reversed by a single injection of naloxone. Injection of estradiol benzoate, together with progesterone, similarly reduced serum LH levels in ovariectomized rats, and this inhibition was partially reversed by naloxone. A single injection of testosterone propionate decreased serum LH levels in male rats castrated 48 h earlier, and naloxone completely blocked the androgen-induced inhibition of LH secretion. Chronic administration of either testosterone propionate or morphine sulfate to castrated male rats prevented the postcastration rise of serum LH. The decrease of hypothalamic LHRH in castrated rats was completely blocked by testosterone propionate or morphine sulfate administration. These results are believed to indicate that hypothalamic opiates are involved in gonadal steroid feedback inhibition of LH release.

Effects of Morphine and Naloxone on Inhibition by Ovarian Hormones of Pulsatile Release of LH in Ovariectomized Rats

The purpose of this study was to determine the effects of morphine and naloxone on pulsatile release of LH in ovariectomized rats treated (or untreated) with ovarian steroids. Ovariectomized rats were given a subcutaneous injection of estradiol benzoate (20 micrograms) or estradiol benzoate (20 micrograms) and progesterone (10 mg) 3 days prior to experimentation. The rats were then given intravenous injections of naloxone (2 mg/kg), morphine (5 mg/kg), or 0.87% NaCl every hour for 3 h. For LH assays, 0.3 ml blood was collected via an atrial cannula 15 min after drug treatment and every 15 min thereafter for 3 h. Pulsatile LH release was suppressed by estradiol benzoate or the combination of estradiol benzoate and progesterone. Naloxone was able to counteract inhibition of pulsatile LH release by these steroids. These results suggest that the endogenous opioid peptides are involved in the negative feedback exerted by estrogen and progesterone on pulsatile LH release. Morphine had no effect on steroid inhibition of pulsatile LH release.

Immunoreactive β-endorphin in the plasma, pituitary and hypothalamus of young and old male rats

Immunoreactive beta-endorphin (IR-beta-ENDO) was measured in the plasma, pituitary, and hypothalamus of young (3-5 mo.) and old (19-23 mo.) male Sprague-Dawley rats, using a specific radioimmunoassay. Plasma IR-beta-ENDO in old male rats (3.44 +/- 0.54 ng/ml) was more than three times higher than values observed in young male rats (1.00 +/- 0.10 ng/ml). Pituitary content and concentration of IR-beta-ENDO also were significantly greater in the old (5.85 +/- 0.51 microgram/gland and 1.17 +/- 0.10 microgram/mg protein) than in the young (3.53 +/- 0.29 microgram/gland and 0.78 +/- 0.06 microgram/mg protein) male rats. The content of IR-beta-ENDO in the hypothalamus of old and young rats was nearly the same (43.45 +/- 2.47 and 49.88 +/- 6.35 ng/hypothalamus, respectively), whereas the concentration of IR-beta-ENDO in the hypothalamus of the old male rats (3.89 +/- 0.25 ng/mg protein) was approximately 50% lower than that observed in the young male rats (7,80 +/- 0.85 ng/mg protein). These changes in plasma, pituitary, and hypothalamic IR-beta-ENDO may contribute to the increase in prolactin and decrease in gonadotropins observed in old male rats, since beta-ENDO administration is known to produce these effects on prolactin and gonadotropin secretion.

Evidence for Hypothalamic Noradrenergic Involvement in Naloxone-Induced Stimulation of Luteinizing Hormone Release

A single injection of the opiate antagonist, naloxone (NAL), resulted in a fourfold increase in serum luteinizing hormone (LH) concentration 20 min after injection. To determine whether noradrenergic neurons were involved, male Sprague-Dawley rats were treated with alpha-methyl-p-tyrosine (alpha-MPT), phenoxybenzamine hydrochloride (PBH), or diethyldithiocarbamate (DDC), all anti-noradrenergic drugs. Reduction of hypothalamic norepinephrine synthesis by alpha-MPT or DDC, or blockade of the alpha-receptors by PBH, resulted in complete suppression of NAL-induced LH release. These results suggest that the NAL-induced increase in LH release is mediated in part via a hypothalamic noradrenergic mechanism.

Reduced ability of naloxone to stimulate LH and testosterone release in aging male rats; possible relation to increase in hypothalamic met5-enkephalin

Abstract Blood luteinizing hormone (LH) and testosterone levels are lower in old than in young male rats. The specific opiate antagonist, naloxone, previously shown to increase serum LH in mature male rats, exhibited relatively little ability to raise serum LH and testosterone levels in old (18–20 mo) as compared to young (4–5 mo) male rats. The brain opiate, met5-enkephalin, which depresses LH, was found to be significantly higher in the hypothalamus of old than of young male rats. These observations suggest that hypothalamic opiates may be partially responsible for the lower serum LH and testosterone levels in old male rats, and for reduced release of these hormones in response to naloxone administration.

Naltrexone partially inhibits the estrogen-induced increase in prolactin secretion and anterior pituitary weight.

Abstract The effects of naltrexone, a specific opiate antagonist, on stimulation by estradiol benzoate (EB) of prolactin (PRL) release and anterior pituitary (AP) weight, were studied in gonadectomized female and male Sprague-Dawley rats. One week after castration, rats were injected for 10 days once daily with 2 μg EB alone, or together with twice daily injections of 2 mg naltrexone/kg body weight (BW). Blood was collected for radioimmunoassay of PRL by orbital sinus puncture on days 0 and 6, and by decapitation on day 11, at which time the AP was quickly removed, weighed and assayed for PRL. Serum PRL concentrations and AP weights were significantly increased by EB administration. These effects of EB were partially but significantly inhibited by naltrexone. These results suggest that endegenous opiates may be involved in the estrogen-induced rise in serum PRL and increase in pituatary weight.