Showing papers on "Prolactin published in 1977"

Prolactin and Murine Mammary Tumorigenesis: A Review

Abstract: It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, ie, initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (eg, chemical carcinogen, physical carcinogens, oncogenic viruses, ets) ie, a permissive action In the promotion phase, prolactin may act as either a promoter or an antipromoter of the "transformed" mammary epithelium In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the "transformed" epithelium In antipromotion the hormone, in the presence of requisite hormones (eg, glucocorticoids), may synergistically induce differentiation (eg, lactation) in the "transformed" epithelium A tumor would result in the former (promotion) but not in the latter (antipromotion) case Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined This is an extremely important area of research which is justifiably receiving increased attention For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression

Galactorrhea: A Study of 235 Cases, Including 48 with Pituitary Tumors

Abstract: An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or...

STIMULATION IN VIVO OF THE SECRETION OF PROLACTIN AND GROWTH HORMONE BY β-ENDORPHIN

Abstract: Morphine sulfate (MS) and the opioid peptide beta-endorphin beta-LPH-(61-91) stimulate prolactin and growth hormone release in steroid-primed and non-treated male rats when injected intravenously or intracisternally. On a molar basis beta-endorphin is at least 20 times more potent than MS, whereas Met5-enkephalin (beta-LPH-(61-65)) and alpha-endorphin (beta-LPH-(61-76)) are devoid of activity at the dose injected (300 mug). The in vivo stimulatory effects of beta-endorphin on prolactin secretion are reversed by the opiate antagonist naloxone. The absence of in vitro effect of MS and beta-endorphin on prolactin and growth hormone secretion by cultured rat pituitary cells suggest that they have a central nervous system site of action.

Hypothalamic-pituitary vasculature: evidence for retrograde blood flow in the pituitary stalk.

Abstract: Retrograde transport of pituitary hormones in the pituitary stalk vasculature was investigated in anesthetized male rats in which the pituitary gland was intact and in animals in which the anterior pituitary, posterior pituitary, or entire pituitary gland had been removed 30 to 60 min before use. Blood was collected for 1.5 to 2 h by free flow from a single long portal vessel through a microcannula, the tip of which was pointed toward the hypothalamus. An arterial blood sample was obtained at the end of each collection of portal blood. The concentrations (ng\ml) of LH, TSH, prolactin, ACTH, α-MSH, and vasopressin, determined by radioimmunoassay, in portal plasma from rats with intact pituitary glands were as follows: LH, 2,320 ± 874 (mean and SE); TSH, 10,180 ± 1,471; prolactin, 4,858 ± 884; ACTH, 82 ± 17.0; a-MSH, 103 ± 17.8; vasopressin, 2.4 ± 1.0. The concentrations of these hormones in arterial plasma of these rats were as follows: LH, <20; TSH, 149 ± 22; prolactin, 25 ± 5.0; ACTH, 0.36 ± 0.05; α-MSH,...

Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss.

Abstract: We tested hypothalamic, pituitary and endocrine function in 19 patients with secondary amenorrhea associated with simple weight loss who did not have anorexia nervosa to evaluate the effects of weight loss on these systems. Thermoregulation at 10 degrees C and 49 degrees C was abnormal and correlated with the percentage below ideal body weight (r = 0.62, P less than 0.02, and r = 0.55, P less than 0.05, respectively). Partial diabetes insipidus was found in 27 per cent of patients with simple weight loss. They had delayed peak plasma luteinizing hormone levels after 10 microgram of luteinizing-hormone-releasing factor, which was correlated with percentage below ideal body weight (r = 0.49, P less than 0.05). Delayed peak plasma thyrotropin levels after 500 microgram of thyrotropin-releasing factor were found. No prolactin, pituitary, thyroid or adrenal abnormalities were present. These findings are qualitatively similar to results of studies in 29 patients with anorexia nervosa, but less severe and less frequently present. We conclude that hypothalamic dysfunction may be caused by weight loss per se.

Effect of Neurotensin, Substance P and Morphine Sulfate on the Secretion of Prolactin and Growth Hormone in the Rat

Abstract: Neurotensin (NT), substance P (SP) and morphine sulfate (MS) elevate plasma prolactin and growth hormone levels in both normal or estrogen-progesterone pretreated male rats. By contrast, steroid priming is required for TRF to exhibit PR.L-releasing activity. Naloxone, an opiate receptor blocker, reverses the stimulatory effect of MS only. Diphenhydramine, a histamine antagonist, inhibits the response to NT, SP and MS without affecting the response to TRF. These results suggest the involvement of a histaminic step in the action of NT, SP and MS. TRF, NT and SP do not appear to stimulate PRL and GH through activation of an opiate receptor. (Endocrinology 100: 751, 1977)

Effects of Starvation in Rats on Serum Levels of Follicle Stimulating Hormone, Luteinizing Hormone, Thyrotropin, Growth Hormone and Prolactin; Response to LH-Releasing Hormone and Thyrotropin-Releasing Hormone

Abstract: Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of ¼ ad libitum food intake (chronically starved), 7 days complete food removal and 2 weeks of ¼ ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups...

Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans.

Abstract: A dose of 2.5 g of gamma-hydroxybutyric acid (GHB) was administered intravenously to 6 healthy male volunteers. A significant increase in plasma GH was observed at 30, 45, 60 and 90 min after injection. The plasma prolactin level increased significantly at 45 and 60 min after GHB injection. These responses were not found after the saline vehicle injection in the same subjects. It is conceivable that GHB could modify the release of serotonin from the nerve terminals and then stimulate the release of GH and prolactin.

Isolation of gamma-amino butyric acid from pig hypothalami and demonstration of its prolactin release-inhibiting (PIF) activity in vivo and in vitro.

Abstract: A non-retarded fraction with prolactin-release inhibiting factor (PIF) activity obtained by chromatography of a concentrate of porcine hypothalami on carboxymethyl-cellulose was chromatographically distinct from catecholamines. This fraction was purified further by six steps involving chromatography on Sephadex G-25, countercurrent distribution, free-flow electrophoresis, and chromatography on triethylaminoethyl cellulose. The PIF-active substance was isolated and identified as gamma-amino-butyric acid (GABA) by: 1) amino acid analyses using sodium as well as lithium-based buffers for resolution of biological fluids, 2) thin-layer chromatography of underivatized material as well as phenylthiocarbamyl derivatives, and 3) mass spectroscopy. Natural and synthetic GABA inhibited prolactin, but not LH release in vitro from isolated rat pituitary halves at doses as low as 0.1 microgram/ml. The inhibition was proportional to the dose; natural and synthetic GABA possessed identical PIF activity. Synthetic GABA also decreased prolactin release in monolayer cultures of rat pituitary cells and inhibited TRH-stimulated prolactin release. The inhibition of prolactin release in vitro by GABA could not be blocked by perphenazine, which inhibits PIF activity of catecholamines. GABA also suppressed prolactin release in vivo, although large doses were needed. Either rapid iv injection or infusion of GABA in doses of 1 to 100 mg in rats significantly decreased serum prolactin levels, which were previously elevated by pretreatment with monoiodotyrosine perphenazine, chlorpromazine, haloperidol, or sulpiride. beta-hydroxy GABA significantly depressed prolactin release, but beta-(p-chlorophenyl)-GABA (Lioresal, CIBA) and 4 other analogs of GABA were not effective in vivo and/or in vitro. The results indicate that GABA can inhibit prolactin release by a direct action on the pituitary gland, but whether this effect is physiologically meaningful still remains to be determined.

Prolactin-like immunoreactivity: localization in nerve terminals of rat hypothalamus.

Abstract: Antibodies to rat prolactin were used in immunohistochemical studies of the hypothalamus and preoptic area of the rat. Evidence was obtained that a protein immunochemically related to prolactin was stored in networks of nerve terminals of many hypothalamic areas such as the arcuate nucleus, the dorsomedial hypothalamic nucleus, and periventricular regions of the hypothalamus and preoptic area. The neuronal storage of a prolactin-like protein in the hypothalamus was unaffected by hypophysectomy.

Nascent prehormones are intermediates in the biosynthesis of authentic bovine pituitary growth hormone and prolactin

Abstract: Major translation products of bovine pituitary RNA in a wheat germ cell-free system were identified as larger forms (prehormones) of growth hormone and prolactin containing amino-terminal extensions of 26 or 27 and 30 amino acid residues, respectively. However, translation of bovine pituitary RNA in the wheat germ cell-free system in the presence of microsomal membranes prepared from canine pancreas or bovine pituitary yielded products that were of the same size as authentic growth hormone and prolactin; by partial amino-terminal sequence analysis they were shown to contain the correct unique amino-terminal sequence of prolactin and the two correct amino termini of authentic growth hormone; moreover, they were found to be segregated within the microsomal vesicles in that they were largely inaccessible to degradation by proteolytic enzymes. When microsomal membranes were present after rather than during translation, prehormones were neither cleaved nor segregated. These results strongly suggest that the synthesis and segregation of the authentic hormone observed in the presence of membranes proceeds via a nascent prehormone rather than a completed prehormone.

Regulation of prolactin release by endogenous opiates.

Abstract: ENDORPHINS, the endogenous peptides recently isolated and identified in brain have been implicated in regulation of pain1–4. But their wide distribution throughout the brain5–7 and their profound behavioural effects after central administration8 suggest an involvement in other central nervous system processes. Immunohistochemical identification of these endorphins (refs 9, 10 and F. Bloom, personal communication) in hypothalamic neurones indicated that neuroendocrine effects are probable. Morphine was previously reported to block ovulation, while more recently, morphine11 and endorphins12–14 were observed to stimulate release of prolactin and growth hormone. Yet, these observations have not established a direct, tonic participation of endorphins in hypothalamic and anterior pituitary function. The absence of any direct action of opiate antagonists has been taken as an argument against any tonic role of endorphins. Recent reports indicate, however, that opiate antagonists do modify on-going central processes. For example, naloxone and naltrexone lower pain threshold in appropriate conditions in man and experimental animals15–18. Using naltrexone as a tool to block opiate receptor function, we have explored whether endorphins are tonically involved as a putative neurotransmitter in the regulation of prolactin release. The results presented here demonstrate a new instance where an opiate antagonist modifies normal function. The data agree with a preliminary report indicating that naloxone reduced prolactin release in immature female rats19.

Prolactin–progesterone antagonism in self regulation of prolactin receptors in the mammary gland

Abstract: THE role of prolactin during growth of the mammary gland and in lactation is well established (see ref. 1 for review) and the antagonising action of progesterone on lactogenesis (but not on mammary growth) has been recognised2–4. A specific receptor for prolactin has been described5 and purified6 and it seems that the level of this receptor in the target cells is very sensitive to hormonal environments and might be one of the essential parameters which modulates the intensity of prolactin action. Titration of this receptor under controlled hormonal conditions has been mainly performed in the liver and its concentrations found to be sensitive to oestrogens7; this effect may be amplified or even mediated by prolactin itself8. We have shown9 that the number of prolactin receptors in the mammary gland of pregnant or lactating rabbits undergoes a sudden increase at the onset of lactation but that the Ka of the receptor–hormone interaction remains constant. The question arises as to which hormonal environment is required for this amplification; is the inhibitory action of high progesterone levels on lactogenesis associated with a reduction of receptor concentrations? We describe here a study of this possibility and of the positive regulation of prolactin on its own receptors in the rabbit mammary gland. We extend to the mammary gland the stimulating effect of prolactin on the levels of its receptors and demonstrate an antagonising action of progesterone on this process.

Testicular LH binding in the hamster: modification by photoperiod and prolactin.

Abstract: Suppression of testicular weight and activity induced in the hamster by light deprivation can be partially reversed by treatment with prolactin (PRL). The present study investigates the possibility that the stimulatory effect of PRL in this preparation may be mediated through increased LH binding. on LH binding while PRL alone or in combination with LH+FSH increased binding to levels greater than the long light controls. Peripheral testosterone concentrations reflected the level of LH binding.

Prolactin: A diabetogenic hormone

Abstract: During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in a second OGTT. — Human PRL or CB 154 had no significant influence on insulin release due to glucose in the perfused rat pancreas. — These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours.

Evidence for a role of prolactin in prostate and seminal vesicle growth in immature male rats.

Abstract: To determine if prolactin secreted endogenously by anterior pituitary grafts could augment male accessory organ weights, single anterior pituitary grafts were placed under the kidney capsule of male rats, whereas control animals received a graft of muscle. Three weeks after transplantation, the animals were sacrificed by decapitation and a significant increase in plasma prolactin was observed, which was accompanied by a highly significant increase in the weights of seminal vesicles, ventral and dorsal prostates, and adrenals. To determine the importance of testicular steroids in the response, animals were castrated. The increases in prolactin, seminal vesicle and ventral and dorsal prostate weights still occurred whether or not a small dose of testosterone replacement therapy was employed. In the presence of the pituitary graft, adrenal weight usually increased in these animals as well. To rule out a requirement for adrenal steroids in the response, adrenalectomized-castrate animals were also studied, and...

Further evidence that serotonin is a neurotransmitter involved in the control of prolactin secretion.

Abstract: Administration of a new specific serotonin uptake inhibitor, fluoxetine, depressed the firing rate of raphe neurons A highly significant increase in serum prolactin levels was observed after ip injection of 30 mg/kg of 5-hydroxytryptophan (5-HTP) in male or female rats pretreated with 10 mg/kg (ip) of fluoxetine Neither 5-HTP nor fluoxetine given separately had any effect on serum prolactin levels In animals pretreated with methysergide the combination of fluoxetine and 5-HTP did not increase significantly serum levels of prolactin In addition, the serotonin agonist quipazine elevated significantly serum prolactin levels in male and female rats The results of this study strengthen the idea that 5-HTP is acting via serotonin-containing neurons that influence anterior pituitary prolactin release, and that serotonin receptor activation leads to prolactin release

Alterations in basal and TRH-stimulated serum levels of thyrotropin, prolactin, and thyroid hormones in starved obese men.

Abstract: To investigate further the alterations in pituitary-thyroid function seen during starvation, we have measured basal and TRH-stimulated serum levels of thyrotropin (TSH), prolactin (PRL), growth hormone, thyroxine (T4), triiodothyronine (T3), free T4, free T3, and reverse T3 during prolonged fasting in seven obese men. Fasting was associated with a significant decrease in serum (4, (3, and free T3, while there was an increase in serum reverse T3; these values tended to return toward pre-fast levels as the fast continued beyond 3 weeks. No significant changes were seen in basal serum TSH, PRL, growth hormone, or free T4. Although the TSH response to TRH was diminished during fasting, PRL, T4, and T3 responses were unchanged. In addition to transient alterations in the peripheral metabolism of T4, these findings suggest that alterations in the thyroid hormone binding capacity of serum carrier proteins may occur during fasting. The blunted TSH response to TRH despite reduction of serum T3 concentration suggests that subtle alterations in hypothalamic-pituitary function may also occur.

Effect of Dexamethasone on Prolactin and TSH Responses to TRH and Metoclopramide in Man

Abstract: We studied the effects of administration of dexamethasone, 2 mg orally every 6 h, for 5 days on the thyrotropin-releasing hormone (TRH)-induced release of prolactin (PRL), thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4) in 9 normal men and on the metoclopramideinduced release of PRL in 7 normal men. Dexamethasone suppressed the baseline serum levels of PRL, TSH and T3. The administration of dexamethasone blunted the PRL and TSH response to TRH; the blunted TSH response resulted in a decreased T3 and T4 response to TRH after dexamethasone. Following dexamethasone administration, the PRL response to metoclopramide, a dopamine antagonist which acts at the hypothalamicpituitary level to stimulate PRL secretion, was blunted in 7 normal men. The data suggest that short-term administration of pharmacological doses of glucocorticoids suppress the secretion of PRL and TSH by a direct effect on the anterior pituitary gland.

Evolution of prolactin receptors in rabbit mammary gland during pregnancy and lactation.

Abstract: The numbers and affinity of prolactin receptors in the rabbit mammary gland were determined during pregnancy and early lactation under conditions in which the endogenous lactogenic hormone was depleted by means of the compound CB 154. In untreated rabbits the number of prolactin binding sites per mg protein increased from 25 ± 3 (SE) fmol at Day 14 of gestation to 54.8 ± 5.8 fmol/mg at Day 22, after which binding declined to 14.2 ± 8.5 fmol/mg, then increased in late pregnancy and during lactation to 110.5 ±11.5 fmol/mg at Day 28. In animals treated with CB 154, binding was always higher than in non-treated animals, with a peak during pregnancy of 149 ± 24 fmol/mg at Day 22. After declining in late pregnancy, the number of receptors was highest at Day 6 of lactation (257.4 ± 34.6 fmol/mg). There is an almost linear increase in the weight of the mammary gland from Day 14 of pregnancy until Day 6 of lactation and this increase is unaffected (except at Day 6 of lactation) by CB 154 treatment. It was observed...