Joseph Meites

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.

Relation of endogenous opioid peptides and morphine to neuroendocrine functions

Abstract Morphine and the endogenous opioid peptides (EOP) exert similar effects on the neuroendocrine system. When adminstered acutely, they stimulate growth hormone (GH), prolactin (PRL), and adrenocorticotropin (ACTH) release, and inhibit release of luteinizing hormone (LH), follicle stimulating hormone (FSH),and thyrotropin (TSH). Recent studies indicate that the EOP probably have a physiological role in regulating pituitary hormone secretion. Thus injection of naloxone (opiate antagonist) alone in rats resulted in a rapid fall in serum concentrations of GH and PRL, and a rise in serum LH and FSH, suggesting that the EOP help maintain basal secretion of these hormones. Prior administration of naloxone or naltrexon inhibited stress-induced PRL release, and elevated serum LH in castrated male rats to greater than normal castrate levels. Studies on the mechanisms of action of the EOP and morphine on hormone secretion indicate that they have no direct effect on the pituitary, but act via the hypothalamus. There is no evidence that the EOP or morphine alter the action of the hypothalamic hypophysiotropic hormones on pituitary hormone secretion; they probably act via hypothalamic neurotransmitters to influence release of the hypothalamic hormones into the pituitary portal vessels. Preliminary observations indicate that they may increase serotonin and decrease dopamine metabolism in the hypothalamus, which could account for practically all of their effects on pituitary hormone secretion.

Hypothalamic Control of Prolactin Secretion

Publisher Summary This chapter emphasizes the current concepts and observations hypothalamic control of prolactin secretion. The regulation of prolactin secretion is exerted by the hypothalamus, and involves the action of a prolactin-inhibiting factor (PIF), a possible prolactin-releasing factor (PRF), catecholamines, serotonin, and other biogenic amines—all produced in the hypothalamus. Some other agents that stimulate or inhibit prolactin secretion including estrogen, the suckling stimulus, stresses, several drugs, and prolactin, act through hypothalamic mechanism. However, there are some hormones and drugs that can directly influence the anterior pituitary to increase or decrease prolactin secretion, although several of these also can act through the hypothalamus. The interference with hypothalamic pathways to the anterior pituitary by appropriate hypothalamic lesions, stalk section, pituitary transplantation or by administration of certain drugs, results in augmented prolactin release. PIF release from the median eminence is at least partially under the regulation of biogenic amines. The physiological importance of circulating prolactin in controlling secretion of pituitary prolactin remains to be elucidated. The ability of many drugs to either increase or depress prolactin release suggests a useful approach for controlling the secretion and functions of prolactin in the organism.

Reproductive Capacity of Aging Female Rats

Multiparous female Long-Evans rats, 20 months or older, were seen to progress from irregular estrous cycles to a constant-estrous syndrome to a series of irregular pseudopregnancies to an anestrous state. An animal in constant estrus was characterized by ovaries with well developed and sometimes cystic follicles, no corpora lutea, an estrogen-stimulated uterus, and an anterior pituitary that appeared normal. Repeatedly pseudopregnant rats had long diestrous periods of variable length, ovaries with many corpora lutea, uteri with numerous secretory glands, and anterior pituitaries that often showed hemorrhagic or small tumorous areas. Anestrous rats had small, atrophic ovaries with no obvious follicular or luteal elements, atrophic uteri, and large pituitary tumors. Twice-daily injections of L-dopa induced the resumption of regular or irregular estrous cycles in most constant-estrous but not in pseudopregnant or anestrous rats.

Selective Actions of Prolactin on Catecholamine Turnover in the Hypothalamus and on Serum LH and FSH

The effects of prolactin (PRL) administration on catecholamine turnover in various brain regions of ovariectomized rats were determined by observing the decline of dopamine and norepinephrine concentrations after alpha-methyltyrosine (alphaMT) administration. PRL had no effect on the steady state concentration of dopamine in the median eminence, anterior hypothalamus and corpus striatum or on the norepinephrine concentration in the anterior hypothalamus. However, PRL selectively enhanced dopamine turnover in the median eminence and anterior hypothalamus after a latent period of 10-26 h. In addition, PRL administration significantly decreased serum concentrations of LH and FSH. These results suggest that the PRL-induced increase in activity of dopaminergic neurons in the median eminence or anterior hypothalamus may be responsible for the reduction of the post-castration rise in serum concentrations of LH and FSH.

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.

Serum Prolactin Levels in Rats with Pituitary Transplants or Hypothalamic Lesions

Serum prolactin levels were determined by radioimmunoassay in hypophysectomized, ovariectomized rats bearing 0, 1, 2, or 4 anterior pituitaries (AP) underneath the kidney capsule at 1, 2, 4, 6, 8, and 10 weeks after transplantation. Rats with no AP transplants had barely detectable levels of serum prolactin, whereas rats with 1 AP transplant from female cycling rats had serum prolactin values as high as those seen in estrous rats (120 ng/ml serum). In rats bearing 2 AP transplants, serum prolactin increased to 170 ng/ml serum, whereas 4 AP transplants elevated serum prolactin to 250 ng/ml, which is about equivalent to that in lactating postpartum rats (280 ng/ml). Injections of estradiol benzoate (1 µg/day for 5 days) into rats bearing 0, 1, 2, or 4 AP transplants, beginning 10 weeks after transplantation, increased serum prolactin over pre-treatment levels, except in the rats with no pituitary transplants. Bilateral lesions placed in the median eminence or anterior hypothalamus of ovariectomized rats significantly increased serum prolactin to 125 and 85 ng/ml, respectively, as compared with sham-lesioned controls (20 ng/ml). Posterior hypothalamic lesions increased serum prolactin concentration slightly and lesions in the amygdaloid nuclei had no effect. These results indicate that removal of hypothalamic inhibition of prolactin release by pituitary transplantation or by appropriate lesion placement in the hypothalamus results in elevated serum prolactin levels.

Effects of L-tryptophan and restraint stress on hypothalmic and brain serotonin turnover, and pituitary TSH and prolactin release in rats

Abstract The dose response and time course effects of L-tryptophan and restraint stress on the metabolism of serotonin and release of thyroid stimulating hormone (TSH) and prolactin (PRL) were tested in male rats. Both treatments increased serotonin turnover in the hypothalamus (H) and remaining brain tissue minus the cerebellum (brain) as determined by enhanced accumulation of serotonin following monoamine oxidase (MAO) inhibition. L-tryptophan but not restraint stress elevated levels of tryptophan in the cerebellum. Both L-tryptophan and restraint stress inhibited TSH release and stimulated PRL release. These findings indicate that enhanced rates of serotonin turnover produced by L-tryptophan and physical restraint are associated with inhibition of TSH and stimulation of PRL release from the anterior pituitary.

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.

Differential Effects of Dopamine Agonists and Haloperidol on Release of Prolactin, Thyroid Stimulating Hormone, Growth Hormone and Luteinizing Hormone in Rats

The dose-response effects of apomorphine and ET-495 (piribedil), 2 specific dopamine (DA) receptor stimulators, and haloperidol, a DA receptor blocker, were tested on the secretion of prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH) and luteinizing hormone (LH) in male rats. Both apomorphine and piribedil reduced serum PRL and TSH levels, stimulated GH release at low but not at high doses and either had no effect or tended to reduce serum LH levels. The minimal effective dose of apomorphine for reducing PRL by 30 min was 0.01 mg/kg; TSH inhibition was observed with a dose of 0.1-0.3 mg/kg. The inhibitory effects of apomorphine (1.0 mg/kg) on PRL and TSH levels were maximal by 15 min and diminished by 120 min; plasma GH was highest 120 min after injection. Thyroidectomy (10 days) markedLH elevated serum TSH, had no effect on serum PRL and inhibited the ability of apomorphine (0.1 or 0.3 mg/kg) to reduce TSH but not PRL levels. These observations may indicate that separate dopaminergic control mechanisms exist for TSH and PRL secretion. Administration of haloperidol elevated serum PRL, tended to lower TSH, dramatically reduced GH and had no effect on LH levels. Haloperidol pre-treatment blocked the effects of apomorphine on PRL, TSH, and GH secretion. The overall results of this study indicate that DA agonists inhibit PRL and TSH, stimulate GH but do not stimulate LH release in male rats.