Showing papers on "Prolactin published in 1985"

Dopamine: a prolactin-inhibiting hormone.

Abstract: A. Introduction DOPAMINE (DA) is an interesting and versatile compound. In the central nervous system (CNS) it is involved with the control of fine movements and mental processes. Its association with disorders such as Parkinsonism and schizophrenia is well recognized. In the hypothalamo-hypophysial axis, DA is the primary physiological inhibitor of PRL secretion. Currently, this catecholamine represents the only nonpeptidergic hypothalamic agent with a well defined hypophysiotropic function. By virtue of its dual role as a neurotransmitter and a hormone, DA provides perhaps the best example of neuroendocrine interactions. It also possesses a more universal property. In all hormonal systems studied thus far, whether at the hypothalamic, posterior pituitary, or anterior pituitary level, DA functions as an inhibitor. Perhaps the common denominator to these diverse cells is the presence of D2 DA receptors, which are negatively linked to the adenylate cyclase system.

A prolactin-inhibiting factor within the precursor for human gonadotropin-releasing hormone

Abstract: The cloned complementary DNA sequence encoding the human gonadotropin-releasing hormone (GnRH) precursor protein was used to construct an expression vector for the bacterial synthesis of the 56-amino acid GnRH-associated peptide (GAP). GAP was found to be a potent inhibitor of prolactin secretion and to stimulate the release of gonadotropins in rat pituitary cell cultures. Active immunization with peptides corresponding to GAP sequences led to greatly increased prolactin secretion in rabbits.

Prolactin stimulation of maternal behavior in female rats

Abstract: Inexperienced, hypophysectomized female rats treated with steroids were used in experiments to investigate the roles of the pituitary gland and prolactin in the expression of maternal behavior. Administration of ovine prolactin or treatment with ectopic pituitary grafts, which release prolactin into the circulation, stimulated maternal care in these females toward rat young. Steroid treatment alone, while stimulating maternal behavior in rats with intact pituitary glands, did not facilitate maternal responsiveness in hypophysectomized females. These findings indicate a stimulatory behavioral role for pituitary prolactin in the establishment of maternal care and suggest that exposure to prolactin during pregnancy helps to stimulate the immediate onset of maternal behavior at parturition.

Pregnancy and the hyperprolactinemic woman.

Abstract: HYPERPROLACTINEMIA has been found to be the cause of infertility in about one third of women presenting with this problem1 2 3 Hyperprolactinemia may impair the hypothalamic–pituitary–ovarian axis at several levels, with the primary site of inhibition probably at the hypothalamic level4 , 5 Studies of gonadotropin secretion in hyperprolactinemic subjects sometimes show decreased pulsatile secretion,6 , 7 which reverts to normal in most women when hyperprolactinemia is corrected by bromocriptine treatment6 , 7 Pituitary responsiveness to gonadotropin-releasing hormone is normal in such women, however, and a normal pattern of gonadotropin pulsatile secretion is restored with small, repetitive doses of the hormone7 Such data support the concept that

Identification by Plaque Assays of a Pituitary Cell Type that Secretes Both Growth Hormone and Prolactin

Abstract: Sequential application of reverse hemolytic plaque assays for GH and PRL revealed the presence of individual pituitary cells that released both hormones. These dual cells accounted for approximately one third of all GH and/or PRL secretors in 24-h pituitary cultures derived from male rats. Additional studies in which a different version of the plaque assay and double-staining immunocytochemistry were applied separately to dispersed pituitary cells from males yielded results that were virtually identical. These results suggest that mammosomatotropes, cells that secrete both GH and PRL, may exist in pituitaries of normal rats. (Endocrinology 116: 734-737,1985)

Ontogeny of Prolactin Cells in Neonatal Rats: Initial Prolactin Secretors also Release Growth Hormone*

Abstract: Reverse hemolytic plaque assays and immunocytochemistry were used to monitor the ontogeny of individual hormone-secreting and hormone-containing cells in rats. Monodispersed anterior pituitary cells from fetal rats (sex unspecified) and neonatal rats of each sex were cultured for 24 h and then subjected to immunocytochemistry or plaque assays for PRL or GH. PRL secretors first appeared in appreciable numbers in cultures from 4-day-old animals, and by day 5, they accounted for 8–12% of all cells in culture. The percentage of GH secretors rose to a peak on day 5 (comprising ∼40% of all cells), when the values were slightly higher than those observed previously in adults. The percentage of cultured cells from 4- to 5-day-olds that released PRL or GH was not influenced by the sex of the donor animal and was consistent with immunocytochemical estimates. Using a sequential plaque assay that enabled the detection of both GH and PRL release from the same cells, we found that of every 100 pituitary cells from 5-da...

Effects of endogenous opioid peptides and opiates on luteinizing hormone and prolactin secretion in ovariectomized rats

Abstract: Adult female rats were implanted with permanent cannulae in the third ventricle of the brain and ovariectomized. 3 weeks later, blood samples were withdrawn every 5 min from intraatrial cannulae placed the previous day. After a control sampling period of 30 min, the rats received an intraventricular bolus injection of saline (2 microliter) or beta-endorphin (beta E; 10 micrograms); sampling was continued for an additional 2 h. Saline injection caused no effect on luteinizing hormone (LH) and prolactin (PRL) secretion. beta E stimulated PRL secretion within 5-10 min, the values peaked in the next 10 min. Thereafter, as PRL levels fell, a suppression of LH secretion became apparent. Inhibition of LH release started 20-35 min after beta E injection and lasted for 35-65 min. The antecendent PRL secretion was apparently not responsible for the observed delayed LH response, since blockade of PRL response with bromocriptine failed to affect the beta E-induced LH suppression. Further, continuous intraventricular infusion of beta E (5 or 10 micrograms/h) for 3 h markedly suppressed the amplitude and frequency of LH episodes in long-term ovariectomized rats. Bolus intraventricular injection of other endogenous opioid peptides and opiate receptor agonists produced different PRL and LH responses. Dynorphin (10 micrograms) similarly suppressed LH release but was only moderately effective in stimulating PRL. Leucine enkephalin (50 micrograms) stimulated LH and inhibited PRL release, while methionine-enkephalin (50 micrograms) selectively stimulated PRL release. The methionine-enkephalin analogs, FK-33824 (50 ng) and DALAMID (50 micrograms), evoked sequential PRL and LH responses similar to those seen after beta E injection. Interestingly, morphiceptin (a specific mu receptor agonist; 10 micrograms) markedly suppressed LH release, but only sparingly stimulated PRL release. Delta receptor peptide (a specific delta receptor agonist; 10 micrograms) selectively suppressed LH release. Bremazocine (a specific kappa receptor agonist; 0.5 mg/kg) administered intravenously suppressed LH release selectively. These studies show that of the four endogenous opioid peptides tested beta E was most effective in evoking sequential PRL and LH responses, and these effects may be mediated by either epsilon receptors or multiple opiate receptor subtypes; stimulation of kappa receptors by bynorphin or bremazocine suppressed LH release, and further studies would be needed to understand the mode of action of the two enkephalins and the delta opiate receptors in eliciting disparate PRL and LH responses.

Long term effects of cyclophosphamide on testicular function.

Abstract: Thirty men treated in childhood with cyclophosphamide for a mean of 280 days were assessed at a mean of 12.8 years after treatment for hormone concentrations and spermatogenesis. Four were azoospermic, nine oligospermic, and 17 normospermic. There was a significant inverse correlation of sperm density with cyclophosphamide dosage and duration of treatment. After a further mean follow up of 7.2 years three patients who were previously oligospermic and one who was azoospermic had normal sperm counts. All patients had normal sexual characteristics and libido. Serum androgen and prolactin concentrations did not differ significantly between patients and controls. Raised basal and stimulated follicle stimulating hormone concentrations were in keeping with impaired spermatogenesis. All patients had significantly raised luteinising hormone responses on stimulation with luteinising hormone releasing hormone. The results suggest compensated Leydig cell failure, and patients with this condition require long term evaluation of testicular function. Potential recovery of spermatogenesis with time requires appropriate counselling and contraceptive advice.

Preoptic catecholamine, GABA, and glutamate release in ovariectomized and ovariectomized estrogen-primed rats utilizing a push-pull cannula technique.

Abstract: The push-pull cannula technique was used to evaluate the role of the medial preoptic/anterior hypothalamic area (MPO) in regulating pituitary luteinizing hormone (LH) and prolactin release. The concentrations of the three catecholamines--dopamine, norepinephrine (NE), epinephrine (E)--and gamma-aminobutyric acid (GABA) and glutamate could be measured in 15-min fractions at which interval blood samples for LH and prolactin determination were also collected. Comparison of neurotransmitter release rates into the MPO were made between ovariectomized and ovariectomized estradiol benzoate treated rats. Release of the neurotransmitters occurred in a pulsatile manner, the release episodes for each transmitter appeared to be independent of the others. No direct correlation between neurotransmitter release episodes and blood LH or prolactin levels could be established. The release of GABA was significantly lower and that of NE and E higher in ovariectomized animals in comparison to estrogen-primed ovariectomized animals under negative feedback conditions. In the afternoon, however, when the estrogen stimulated LH and prolactin release, preoptic GABA release was low, whereas preoptic NE and particularly E release rates were high. Conspicuously high dopamine and NE release episodes were observed in estrogen-primed animals at noon, i.e., prior to the expression of the positive feedback signal. This may reflect a biochemical correlate to the so-called critical period. No consistent differences between ovariectomized and ovariectomized estradiol-17 beta benzoate treated animals were observed for preoptic glutamate release rates. The data show that preoptic GABA release rates show generally an inverse pattern to NE and E release and therefore also to blood LH and prolactin levels. No direct mathematical correlation between any of the neurotransmitter release rates and blood hormone levels could be established.

Psychoneuroendocrine stress responses and mood as related to the menstrual cycle.

Abstract: Psychoneuroendocrine stress responses were studied in normally ovulating women in the follicular, ovulatory, and luteal phases of two consecutive menstrual cycles. Psychologic stress was induced by having the subjects perform a battery of cognitive tasks under time pressure. Blood samples were drawn after each session for radioimmunoassay of 17 beta-estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, prolactin, cortisol, and androstenedione. Urine samples were obtained for estimation of adrenaline, noradrenaline, and cortisol. The results showed that psychoneuroendocrine stress responses as estimated by urinary excretion of adrenaline and noradrenaline varied significantly across the menstrual cycle, the highest values being obtained in the luteal phase. Self-reported mood and somatic symptoms showed distinct phase-related changes, with more negative mood states predominating in the luteal and menstrual phases and increased positive mood states in the follicular and ovulatory phases.

Progestin action and progesterone receptor structure in human breast cancer: a review.

Abstract: Publisher Summary This chapter discusses the current information about progestin action, and progesterone receptors (PR) structure and function It presents a recent study in which a progestin-responsive human breast cancer cell line has been used to study the biochemical mechanisms involved in progesterone action Progesterone is essential for human breast alveolar gland development and growth It is not only a mitogenic hormone but also acts in synergy with estradiol to prime the mammary gland to respond to mitogens like prolactin, glucocorticoids, and growth hormone At puberty, estradiol induces mammary duct formation As the hypothalamic-pituitary-ovarian axis matures, there is a brief phase of anovulatory cycles during which the mammary gland is influenced principally by estrogens Once ovulation is established, corpus luteum produces progesterone, which stimulates growth of the lobuloalveolar structures During the reproductive years, progesterone promotes differentiation of alveolar cells into secretory cells, and dilation of the duct system In conjunction with prolactin and other metabolic hormones, progesterone stimulates lipid droplet formation, and secretory activity While prolactin and growth hormone are the most important pituitary hormones affecting growth of the mammary gland during pregnancy, it is estradiol and progesterone that prevent the full expression of their secretory effects on the mammary epithelium At parturition, the sudden withdrawal of these two hormones permits the breast to respond to the lactogenic hormones

Long-term effects of cranial irradiation on endocrine function in children with brain tumors. A prospective study.

Abstract: This study prospectively evaluated the endocrine function of 11 children treated with cranial irradiation (CRT) for brain tumors. All tumors were remote from the hypothalamic-pituitary axis. Children were studied before treatment and at 3, 6, and 12 months after the completion of CRT. T4, thyroid-stimulating hormone, prolactin, plasma cortisol, and urinary follicle-stimulating hormone and luteinizing hormone values were normal before and after treatment in all patients. Growth hormone (GH) deficiency was identified in 0 of 7 patients before treatment, in 2 of 7 patients 3 months post-CRT, in 9 of 11 patients 6 months post-CRT, and in 7 of 8 patients 12 months post-CRT. Growth deceleration was identified in five of seven prepubertal patients. GH deficiency is an extremely common sequelae of CRT, beginning as early as 3 months after the completion of CRT. The deficit is progressive over time.

Low doses of dopamine agonists in the long-term treatment of macroprolactinomas.

Abstract: To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.

A nonmitogenic pituitary function of fibroblast growth factor: regulation of thyrotropin and prolactin secretion

Abstract: The addition of fibroblast growth factor (FGF) to primary cultures of rat anterior pituitary cells modifies their response to thyrotropin-releasing factor in a dose-dependent manner. While the pituitary response to the other releasing factors (corticotropin-releasing factor, growth hormone-releasing factor, and gonadotropin-releasing factor) is not altered, FGF increases both the sensitivity of the cells to thyrotropin-releasing factor and the amounts of prolactin and thyrotropin released. A minimum of 24 hr of preincubation with FGF is required to modify the pituitary response, and maximal effects were observed with 48 and 72 hr of preincubation. The effective doses of FGF are similar to those described for its mitogenic activity (i.e., 1-100 pM), but inhibition of cell growth with 5-fluorodeoxyuridine does not modify the effect of FGF on thyrotropin and prolactin release. These results suggest a novel paracrine, if not autocrine, role of pituitary FGF in the homeostatic mechanisms that regulate the secretion of prolactin and thyrotropin. They also suggest that the biological significance of the presence of FGF in various tissues may not be directly related to its in vitro mitogenic activity.

Vasoactive intestinal peptide-containing neurons in the paraventricular nucleus may participate in regulating prolactin secretion.

Abstract: Vasoactive intestinal polypeptide (VIP) immunoreactivity is present in varicosities and fibers in the hypothalamic paraventricular nucleus (PVN) in normal control animals. Adrenalectomy and lactation combined with colchicine treatment results in the appearance of a large population of VIP-immunopositive cell bodies in the parvocellular part of the PVN. Adrenalectomy, as well as lactation, significantly increases the number of VIP-positive fibers in the external zone of the median eminence. These observations suggest that the VIP-immunopositive neurons in the PVN may participate in regulating prolactin and corticotropin secretion.

In cow anterior pituitary, growth hormone and prolactin can be packed in separate granules of the same cell.

Abstract: The ultrastructural localization of growth hormone and prolactin in cow anterior pituitary was studied by double immunocytochemical labeling using specific antibodies and protein A-gold particles of different sizes. The two hormones were found in specific somatotrophs and mammotrophs as well as in somatomammotropic cells which were multinucleated and predominantly arranged in clusters in the central area of the lobules. In these mixed cells the two hormones were packaged (a) in different granules of the same cell, (b) in the same granules where they were segregated in different portions of the granule content, or (c) in the same granules but evenly intermixed. The relative proportion of these three types of granules varied in somatomammotrophs of different animals. A single large Golgi complex was generally present in somatomammotrophs. Small, immature granules containing either growth hormone or prolactin or both hormones were found randomly distributed along Golgi stacks. This suggests that in these cells the two hormones are processed in the same Golgi cisternae and that mechanism(s) exist(s) to sort out the two hormones from each other.

Hypothalamic gonadotrophin-releasing hormone and pituitary and plasma FSH and prolactin during photostimulation and photorefractoriness in intact and thyroidectomized starlings (Sturnus vulgaris)

Abstract: Changes in concentrations of hypothalamic gonadotrophin-releasing hormone (GnRH) and pituitary and plasma FSH and prolactin were measured in intact and thyroidectomized female starlings (Sturnus vulgaris) after transfer from short to long photoperiods. In intact birds, hypothalamic GnRH did not increase significantly during the first 6 weeks of photo-stimulation, but by 12 weeks, as birds became photorefractory, it had decreased to levels significantly lower than those before photostimulation. In thyroidectomized birds, which did not become photorefractory, hypothalamic GnRH remained high after 12 weeks of photostimulation. Pituitary FSH increased in both intact and thyroidectomized birds; it then decreased to low levels in intact photorefractory birds, but remained high in thyroidectomized birds. Plasma FSH increased to a peak after 2 weeks, but by 6 weeks it had decreased to low levels in both groups. In intact birds there was a 70-fold increase in pituitary prolactin during the first 6 weeks, and levels were still high after 12 weeks of photostimulation. In thyroidectomized birds, pituitary prolactin remained low. The results suggest that while the initial effect of long daylengths is to cause gonadal maturation, the ultimate effect is to switch off the reproductive system.

Impaired growth hormone response to growth hormone releasing factor and insulin-hypoglycaemia in obesity

Abstract: We have previously reported an impaired growth hormone (GH) response and abnormal prolactin release to insulin-hypoglycaemia in obesity We suggested that obese women with an absent prolactin response to hypoglycaemia (‘non-responders’) have a disorder of hypothalamic function We have now investigated the GH response to i v growth hormone releasing factor, GHRF (1–29)NH2, in 14 obese women and nine age-matched normal-weight women We found a significantly reduced GH response to GHRF in the obese women as compared with controls (mean peak · SEM: obese 8·9 · 2 mu/l, controls 28 · 2 mu/l; P >0·01) When the obese women were divided on the basis of their prolactin response to insulin-hypoglycaemia (seven ‘non-responders’, mean weight 102 · 5 kg; seven responders, mean weight 108·8 kg) a similar GH response to GHRF was found between the two groups but the GH response to hypoglycaemia was significantly less in the ‘non-responder’ women (mean peak ‘non-responders’ 10·5 · 3 mu/l, responders 27·4 mu/l; P < 0·05) We conclude that obesity may be characterized by an impaired GH response to both i v GHRF and insulin-hypoglycaemia, which suggests altered hypothalamic-pitui-tary function The finding that the GH response to hypoglycaemia is significantly less in the obese prolactin ‘non-responder’ women supports the hypothesis for a hypothalamic disorder

Elevated growth hormone levels in sera from breast cancer patients.

Abstract: The concentrations of growth hormone (GH) and prolactin (PRL) in the serum of 42 breast cancer patients were determined by radioimmunoassay (RIA). Forty percent of the patients had elevated GH levels while only 17% had elevated PRL levels. These findings suggest a relationship between GH and breast cancer; a weaker correlation exists between PRL and this malignancy. In addition, total lactogens in the serum were measured by a bioassay (BA). The BA/RIA (GH + PRL) ratio was greater in the breast cancer patients than the controls, indicating that variant forms of the hormones with higher than normal biological activity might be present.

Immunocytochemical localization in rat brain of a prolactin release-inhibiting sequence of gonadotropin-releasing hormone prohormone

Abstract: The structure of a precursor protein for gonadotropin-releasing hormone (GnRH) of relative molecular mass 10,000 has recently been deduced from cloned complementary DNA sequences derived from human placental messenger RNA1. The 56-amino-acid peptide representing residues 14–69 of this prohormone exhibits potent inhibition of prolactin secretion2. To investigate whether the same prohormone is synthesized in mammalian brain and describe the anatomical distribution of the prolactin-inhibiting region of this molecule, we have generated antiserum to a synthetic peptide containing residues 40–53 of the human placental precursor. We report here that a substance recognized by this antibody is present in GnRH-containing neurones of the rat brain and appears to coexist with GnRH in secretory granules of nerve terminals in the median eminence. These results indicate homology between hypothalamic and placental prohormones for GnRH and are consistent with the suggestion elsewhere in this issue2 that a prolactin-inhibiting factor (PIF) is generated from this prohormone and cosecreted with GnRH by nerve terminals in the median eminence.

Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.

Abstract: The effect of the continuous exposure to ovine corticotropin-releasing factor (oCRF) was measured in adult male rats. The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values. Additionally, corticotropin-releasing factor (CRF)-treated rats had decreased plasma testosterone levels. The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content. In these animals, CRF markedly inhibited luteinizing hormone (LH) (but not follicle-stimulating hormone [FSH] ), testosterone, and PRL secretion and decreased seminal vesicle weights. All the effects of CRF were mimicked by exogenously administered ACTH. By contrast, with the exception of FSH secretion, which was slightly elevated by CRF, neither CRF nor ACTH were able to significantly modify reproductive parameters in adrenalectomized animals, which suggests that the elevation of circulating levels of adrenal steroids induced by peripherally administered CRF represents major mediators of CRF-induced inhibition of fertility. These results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of the pituitary-adrenal axis, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids. The increased secretion of adrenal steroids by CRF-treated rats is believed to participate in the disruption of reproductive parameters observed in these rats.

Cyclic AMP regulation of eukaryotic gene transcription by two discrete molecular mechanisms

Abstract: In experiments designed to study the mechanism by which peptide hormones binding to their plasma membrane receptors stimulate the expression of specific genes, the transcription of two neuroendocrine genes, prolactin and growth hormone, was analyzed in a rat pituitary cell line. The results showed that cyclic adenosine monophosphate (cyclic AMP) stimulates the transcription of discrete subsets of eukaryotic genes by at least two independent molecular mechanisms. Cyclic AMP stimulated growth hormone gene transcription and phosphorylation of a 19,000-dalton nuclear protein; this appears to reflect direct nuclear actions of the cyclic AMP-dependent protein kinase. In contrast, the stimulation by cyclic AMP of prolactin gene transcription appears to reflect activation of a discrete calcium-dependent event.