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Showing papers on "Prolactin published in 1995"


Journal ArticleDOI
TL;DR: These factors and dysfunctional communication between the nervous, endocrine, and immune systems appear to contribute to the development of autoimmune diseases in the Lewis and BB rats, the OS chicken, and the NOD, MRL, NZB, NZW, and NZB/NZW F1 mice.
Abstract: The concept of an integrated bidirectionally regulated neuroendocrine-immune adaptive response to stress has strong experimental support. The quality and intensity of this coordinated response to stress varies depending upon age, gender, reproductive status, and other genetically determined factors as well as the types and magnitudes of environmental challenges. These factors and dysfunctional communication between the nervous, endocrine, and immune systems appear to contribute to the development of autoimmune diseases in the Lewis and BB rats, the OS chicken, and the NOD, MRL, NZB, NZW, and NZB/NZW F1 mice. Neuroendocrine-immune dysfunction also contributes to the pathogenesis of human autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and others. This review highlights these concepts. It includes discussions on various aspects of the stress response, the hypothalamic-pituitary-adrenal and -gonadal axes, corticotropin releasing hormone, luteinizing hormone releasing hormone, interleukin-1 and -6, corticosteroids, estrogens, testosterone, dehydroepiandrosterone, growth hormone, prolactin, and thyroid hormone. The role of the nervous and endocrine systems in regulating thymopoiesis and T cell development is also emphasized.

479 citations


Journal ArticleDOI
TL;DR: The purpose of this review is to provide an account of the recent advances in PRL, which suggests that the hormone is perhaps a prohormone, which is synthesized as a precursor molecule and then converted to different bioactive forms as it traverses the secretory pathway.
Abstract: I. Introduction PROLACTIN (PRL) is one of the most versatile hormones of the pituitary gland in terms of biological actions. More than 100 different and distinct effects of the hormone have been documented (1), ranging from mammary development and initiation of lactation in mammals to osmoregulation in fishes, nesting behavior in birds, and growth and metamorphosis in amphibians. These are far in excess of the reported actions of all other adenohypophyseal hormones combined. But how does a single molecule evoke so many different responses? Studies in the last few years have shown that the hormone exists in several molecular forms, some arising from posttranslational modifications and others from genetically determined factors. Such findings have led to the suggestion that PRL is perhaps a prohormone, which is synthesized as a precursor molecule and then converted to different bioactive forms as it traverses the secretory pathway. The purpose of this review is to provide an account of the recent advances i...

418 citations


Journal ArticleDOI
TL;DR: A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized and has been selected for clinical studies.
Abstract: A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

330 citations


Journal Article
TL;DR: Analysis of data indicates that prolactin may participate in an autocrine/paracrine stimulatory loop within breast tissues and suggest a role for this growth factor in the pathogenesis of breast cancer.
Abstract: The neuroendocrine hormone prolactin is a growth factor required for the proliferation and terminal differentiation of the human breast. These effects are mediated by the prolactin receptor, a member of the growth factor receptor family. Three prolactin receptor isoforms (long, intermediate, and short) have been identified in the rat, which differ in the length of their intracytoplasmic domains. In humans, however, only the long prolactin receptor isoform had been identified previously. The expression of the human intermediate prolactin receptor is demonstrated and preliminary evidence for a human short isoform is presented. Heterogeneous expression of prolactin receptor, at the immunoblot and immunohistochemical levels was observed in breast carcinoma specimens. A statistically significant correlation between prolactin receptor and estrogen receptor expression was noted. An autocrine/paracrine role for prolactin within breast tissues was further examined by performing reverse transcription polymerase chain reaction on RNA isolated from cell lines and clinical specimens with prolactin-specific primers. A 585-bp product was observed and found to be identical to human prolactin. The synthesis of prolactin by breast epithelium was confirmed by in situ hybridization analysis of breast tissues and the detection of bio- and immunoreactive prolactin in breast cancer lines. These analyses indicate that the principal site for prolactin expression within the normal or malignant breast residues within the epithelium. These data indicate that prolactin may participate in an autocrine/paracrine stimulatory loop within breast tissues and suggest a role for this growth factor in the pathogenesis of breast cancer.

272 citations


Journal Article
TL;DR: The addition of a panel of anti-human Prl mAbs to T47Dco and MCF7 human breast adenocarcinoma cells suggests that human breast cancer cells synthesize and secrete biologically active Prl.
Abstract: A possible autocrine function of prolactin (Prl) in human breast cancer was explored by the addition of a panel of anti-human Prl mAbs to T47Dco and MCF7 human breast adenocarcinoma cells. mAb 631 and mAb 390 inhibited cell growth by 86 and 68%, respectively, in the estrogen receptor-negative T47Dco cells and by 20 and 71%, respectively, in the estrogen receptor-positive MCF7 cells. Conditioned medium prepared from T47Dco cells was assessed for the presence of Prl-like molecules by its ability to stimulate growth of Prl-responsive Nb2 rat lymphoma cells. Growth of Nb2 cells under the influence of human Prl or conditioned medium was abolished when either solution was pretreated with mAb 390, followed by Immunobead precipitation (Bio-Rad, Melville, NY). T47Dco cells secrete 0.7 microgram lactogen/ml over a 24-48-h period. With the use of reverse transcription-PCR, an expected 612-bp band was detected by ethidium bromide staining, and its similarity to pituitary Prl was confirmed by Southern blot analysis with the use of human Prl cDNA as a probe. A single M(r) 22,000 band, the dominant size of monomeric pituitary Prl, was found in immunoprecipitates of both cell extracts and conditioned medium from T47Dco cells labeled metabolically with [35S]cysteine. These data suggest that human breast cancer cells synthesize and secrete biologically active Prl.

263 citations


Journal ArticleDOI
TL;DR: The results suggest that the cross-talk between steroid hormone receptors and AP-1 leads to an impairment of AP- 1 activity and to an inhibition of involution in the mammary glands implying that programmed cell death in the postlactational mammary gland depends on functional AP-2.
Abstract: Milk production during lactation is a consequence of the suckling stimulus and the presence of glucocorticoids, prolactin, and insulin. After weaning the glucocorticoid hormone level drops, secretory mammary epithelial cells die by programmed cell death and the gland is prepared for a new pregnancy. We studied the role of steroid hormones and prolactin on the mammary gland structure, milk protein synthesis, and on programmed cell death. Slow-release plastic pellets containing individual hormones were implanted into a single mammary gland at lactation. At the same time the pups were removed and the consequences of the release of hormones were investigated histologically and biochemically. We found a local inhibition of involution in the vicinity of deoxycorticosterone- and progesterone-release pellets while prolactin-release pellets were ineffective. Dexamethasone, a very stable and potent glucocorticoid hormone analogue, inhibited involution and programmed cell death in all the mammary glands. It led to an accumulation of milk in the glands and was accompanied by an induction of protein kinase A, AP-1 DNA binding activity and elevated c-fos, junB, and junD mRNA levels. Several potential target genes of AP-1 such as stromelysin-1, c-jun, and SGP-2 that are induced during normal involution were strongly inhibited in dexamethasone-treated animals. Our results suggest that the cross-talk between steroid hormone receptors and AP-1 previously described in cells in culture leads to an impairment of AP-1 activity and to an inhibition of involution in the mammary gland implying that programmed cell death in the postlactational mammary gland depends on functional AP-1.

242 citations


Journal ArticleDOI
TL;DR: In this paper, the authors compared the pattern of liver nuclear protein tyrosine phosphorylation in male and female rats, and found that growth hormone (GH) exerts sexually dimorphic effects on liver gene transcription that are regulated by the temporal pattern of pituitary GH release.

237 citations


Journal ArticleDOI
TL;DR: There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.
Abstract: An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

198 citations


Journal ArticleDOI
TL;DR: It is suggested that decreased serotonergic activity in postmenopausal women might contribute to their vulnerability to affective disorders and estrogen replacement therapy might decrease this vulnerability and might add to the efficacy ofserotonergic antidepressants when warranted.

180 citations


Journal ArticleDOI
TL;DR: No appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolACTin-inhibiting activity of dopamine and atrial natriuretic factor.
Abstract: Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolactin-inhibiting activity of dopamine and atrial natriuretic factor.

143 citations


Journal ArticleDOI
TL;DR: The data available to date indicate that endocrine and pleiotropic para- and autocrine mechanisms of action are involved in a neuropeptide immune network, including GH, PRL and IGF-I as modulators of immune function.
Abstract: Growth hormone-releasing hormone (GHRH), growth hormone (GH), prolactin (PRL) and insulin-like growth factor I (IGF-I) are synthesized and secreted by various immunocompetent cells. In addition, GHRH, GH, PRL and IGF-I receptors are expressed on immune cells. Growth hormone, PRL and IGF-I stimulate the proliferation of immunocompetent cells and modulate humoral and cellular immune functions, i.e. immunoglobuline secretion of B cells, thymulin secretion of thymic epithelial cells, natural killer cell activity, phagocytosis, oxidative burst and killing capacity of neutrophils and macrophages. No clinically significant cellular or humoral immunodeficiency has been found in GH-deficient patients. However, several immunological parameters and functions are altered in GH-deficient patients when compared to normal controls. The data available to date indicate that endocrine and pleiotropic para- and autocrine mechanisms of action are involved in a neuropeptide immune network, including GH, PRL and IGF-I as modulators of immune function.

Journal ArticleDOI
TL;DR: TCDD alters reproductive function in the immature female rat model via effects on the hypothalamic-pituitary axis as well as by direct effects onThe ovary, which is suggested to alter estrous cyclicity and ovulation.

Journal ArticleDOI
TL;DR: The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5- HT2A, or5-HT2C receptors.

Journal ArticleDOI
TL;DR: This transgenic mouse model indicates that TGF alpha overexpression by lactotrophs stimulates the growth of these pituitary cells, and suggests that T GF alpha might play a role in the development of prolactinomas.
Abstract: The PRL-secreting cells of the pituitary gland normally express transforming growth factor-alpha (TGF alpha). To determine the effect of increasing TGF alpha expression in the pituitary, a transgenic mouse model was created in which overexpression of human TGF alpha was directed to the pituitary lactotrophs using the rat PRL promoter. Of the four gene-positive mouse lines, two expressed the messenger RNA corresponding to the transgenic in the pituitary glands. However, in both these lines, expression could only be detected in the female animals. Expression of the transgenic could be detected as early as 1 month of age, but no pathology or developmental abnormalities were detected until the animals reached 6 months, at which time, hyperplasia of the lactotrophs. By the age of 12 months, all of the homozygous transgenic females had developed pituitary adenomas that were immunopositive for PRL. The other hormone-producing cells of the pituitary showed no obvious pathology. The male transgenics developed neither hyperplasia nor adenomas, nor did the gene-positive transgenic lines that did not express the transgene. In no case was an aggressive pituitary tumor seen. This transgenic mouse model indicates that TGF alpha overexpression by lactotrophs stimulates the growth of these pituitary cells. Furthermore, TGF alpha has a highly localized action in the pituitary gland, resulting only in lactotroph hyperplasia and prolactinomas. These observations suggest that TGF alpha might play a role in the development of prolactinomas.

Journal ArticleDOI
TL;DR: It is hypothesize that the reduction in the circulating concentration of GH caused the reduced susceptibility of parous rats to mammary carcinogenesis possibly by decreasing the levels of ER and/or EGF-R in the mammary gland.
Abstract: Administration of a single i.v. injection of 50 mg N-methyl-N-nitrosourea (MNU)/kg body wt to 50- to 60-day old virgin rats, 120-day-old virgin rats, and 120-day-old parous rats (Sprague-Dawley; n = 18-37) resulted in a high incidence of mammary carcinomas in the virgin animals (97.3% in 50- to 60-day-old virgin rats; 75.0% in 120-day-old virgin rats), but mammary carcinomas did not develop in the parous rats. The concentrations in serum of various mammotropic hormones were measured in identical groups of rats at the time of MNU treatment. Growth hormone (GH) concentration was significantly reduced in parous rats, as compared with young or age-matched virgin rats. The concentrations of prolactin, 17 beta-estradiol, progesterone, corticosterone and thyroxine were not significantly altered in the parous rats compared to the two groups of virgin animals. Histological examination of the mammary glands from the three groups of rats showed that the epithelia of the parous animals were in a stage of regression, whereas the mammae of the young virgin rats showed the highest degree of lobulo-alveolar development. The levels of estrogen receptor (ER), epidermal growth factor (EGF) receptor (EGF-R) and GH receptor (GHR) in the mammary glands of the animals were also measured. We found a reduction in the receptor levels for both estrogen and EGF in mammary tissues from parous animals. Receptors for GH were present in normal mammary tissues from both virgin and parous rats. We hypothesize that the reduction in the circulating concentration of GH caused the reduced susceptibility of parous rats to mammary carcinogenesis possibly by decreasing the levels of ER and/or EGF-R in the mammary gland.

Journal ArticleDOI
TL;DR: Involvement of MGF/Stat5 in the signaling by other cytokines indicates that the same factor might be involved in regulation of growth-promoting genes, primarily in hematopoietic cells.

Journal ArticleDOI
TL;DR: Ketoconazole normalizes the blunted prolactin responses to d-fenfluramine and may be an effective method by which to treat depression.

Journal ArticleDOI
TL;DR: It is concluded that protein deficiency in mares increases GH secretion, whereas energy restriction alone does not, a deficiency in energy and(or) protein reduces IGF-I secretion, and prolactin concentrations increase after feeding, even at a time of year when secretion rates are naturally low.
Abstract: Sixteen light horse mares were fed diets of bermudagrass hay and a corn/cottonseed hull-based supplement formulated to contain either 100% (control) or 50% (restricted) of the protein and(or) energy requirements for maintenance in a 2 x 2 factorial arrangement of treatments. Plasma IGF-I, prolactin, cortisol, triiodothyronine, and thyroxine were monitored for 33 d. On the 27th d, frequent blood samples were drawn throughout the day for the measurement of growth hormone (GH), and on the 29th d, an epinephrine challenge and an i.v. glucose tolerance test (IVGTT) were performed in the morning and afternoon, respectively. Restriction of protein and(or) energy reduced (P .1) by restriction of protein and(or) energy. Plasma prolactin concentrations were low throughout the experiment and after the IVGTT, but they increased (P = .003) after feeding. Protein restriction increased (P = .09) the occurrence of GH episodes during the 14-h feeding period on d 27; the greatest effect occurred in the mares restricted in both nutrients. In contrast, energy restriction reduced (P = .05) the GH response to epinephrine injection. We conclude that 1) protein deficiency in mares increases GH secretion, whereas energy restriction alone does not, 2) a deficiency in energy and(or) protein reduces IGF-I secretion, and 3) prolactin concentrations increase after feeding, even at a time of year when secretion rates are naturally low.

Journal ArticleDOI
TL;DR: The natural mating condition reveals the contributions of the short-term and long-term mnemonic devices, establishing the existence of a graded to all-or-nothing transition that is required for the occurrence of PSP.
Abstract: INTRODUCTION IN many female mammals, vaginocervical stimulation (VCS) received during mating modifies sexual responsiveness and initiates or induces several neuroendocrine changes that influence reproductive success. VCS is particularly important in reflexively ovulating species such as the cat and rabbit in which mating directly induces ovulation by increasing hypothalamic LHRH secretion and pituitary LH release. In spontaneously ovulating species such as the rat, mating-induced changes in neuroendocrine function are no less important for reproductive success. In these cases, mating stimulation triggers the release of the PRL required for rescue of the short-lived corpus luteum of the estrous cycle and for the resulting prolongation of progesterone secretion that is necessary for uterine endometrial development and implantation of the blastocyst. The existence of the link between VCS and reproductive function has been known to endocrinologists since the 1930s (1), and there is substantial understanding o...

Journal ArticleDOI
TL;DR: This study investigates plasma baseline cortisol and prolactin secretion in relation to plasma interleukin-6 (IL-6) and soluble IL-2 receptor (sIL-2R) levels in 34 healthy controls and 56 major depressed patients to examine the immune-endocrine relationships.
Abstract: Recently, a complete bidirectional circuit between the immune and neuroendocrine systems has been documented. Previous reports from this laboratory have shown that there are complex reciprocal relationships between immune and hypothalamic-pituitary-adrenal (HPA)-axis function in major depression. To further examine the immune-endocrine relationships, this study investigates plasma baseline cortisol and prolactin secretion in relation to plasma interleukin-6 (IL-6) and soluble IL-2 receptor (sIL-2R) levels in 34 healthy controls and 56 major depressed patients. There were significant positive correlations between IL-6 or sIL-2R and plasma cortisol in major depressed subjects and in the combined group of major depressed and healthy subjects. There were also significant positive correlations between plasma prolactin and sIL-2R concentrations in major depressed subjects and in the combined groups of normal and major depressed subjects.

Journal Article
TL;DR: GH probably exerts its effects as a human macrophage-activating factor through either GH or PRL receptors, without requiring production of IGF-I.
Abstract: Although many effects of growth hormone (GH) and related factors upon the immune system have been demonstrated, few studies have examined the capacity of these factors to modulate human monocyte function in vitro. Assaying a range of mediators, only GH and prolactin (PRL), at 0.3 to 1.0 micrograms/ml, and growth hormone-releasing hormone (GRH) at very high doses, primed monocytes for enhanced hydrogen-peroxide production (H2O2) in response to PMA. GH-induced priming was not caused by endotoxin, nor by production of lymphokines such as IFN-gamma. Exogenous insulin-like growth factor-I (IGF-I), alone or in combination with GH, was without effect, making it unlikely that GH mediates its effects on monocytes via an autocrine/paracrine action of IGF-I. Monocytes specifically bound radiolabeled GH and contained mRNA for the GH receptor and, in some donors, the PRL receptor. Therefore, GH probably exerts its effects as a human macrophage-activating factor through either GH or PRL receptors, without requiring production of IGF-I.

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TL;DR: Evidence is provided for both pituitary and adrenal cortical impairment in CFS and further studies are merited to both confirm and determine more precisely their neurobiological basis so that rational treatments can be evolved.

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TL;DR: The data suggest that cocaine activates the hypothalamic-pituitary-adrenal axis in humans and raises questions concerning the role of dopamine in the mechanism of acute cocaine action in humans.

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TL;DR: The inhibition of the hypothalamo-pituitary-ovarian axis during lactation is mainly due to suckling-induced neuroendocrine reflexes, and it is hypothesized that the nutritional deficit becomes relatively more important during the third and fourth weeks pp.
Abstract: Parturition in the sow is followed by a period of anovulation which is prolonged by lactation. Follicular development and luteinizing hormone (LH) secretion are depressed during the last month of pregnancy. After parturition, LH secretion increases but is again inhibited by the establishment of lactation. Lactating sows are submitted to stimuli originating from the young, whose intensity culminates 3-14 d post-partum (pp), and to high nutrient requirements for milk production. The inhibitory effects of sucklings are imposed during the first 3 d pp and seem to be mediated by the action of opioids at the hypothalamic level. The nutritional deficit constitutes an additional inhibitory factor. As lactation continues, LH secretion progressively increases. A further rise in LH occurs at weaning. Variations in follicle-stimulating hormone (FSH) profiles are less marked. The divergence observed between LH and FSH might be explained by different mechanisms of control; FSH secretion depends mainly on ovarian inhibition whereas LH secretion depends mainly on factors related to lactation. Folliculogenesis progressively resumes during lactation and follicles acquire the ability to respond to the weaning-associated stimuli and begin preovulatory growth. Hormones modified by lactation, such as prolactin, insulin, growth hormone and insulin-like growth factor I, may influence folliculogenesis directly at the ovarian level or via modifications of gonadotrophin secretions. In conclusion, the inhibition of the hypothalamo-pituitary-ovarian axis during lactation is mainly due to suckling-induced neuroendocrine reflexes. We hypothesize that the nutritional deficit becomes relatively more important during the third and fourth weeks pp.

Journal ArticleDOI
TL;DR: The widespread expression of the PRL and GH receptor transcripts in gastric and intestinal mucosal lineages, particularly in epithelia, suggests regulatory roles of these hormones on digestive and immune functions, including metabolism, growth, or differentiation.
Abstract: Distribution of transcripts for prolactin and growth hormone receptors (PRLR and GHR) and their isoforms was characterized in the gastrointestinal (GI) tract from several species by reverse transcription-polymerase chain reaction combined with Southern analysis. Human, rabbit, and fetal and adult rat PRLR and GHR transcripts were detected in isolated gastric glands, gastric cell fractions, and intestinal mucosa lineages. Human PRLR and GHR transcripts were also observed throughout the cancerous progression of the colonic and gastric mucosa from adenomas to colonic liver metastasis and gastrointestinal cancer cell lines at various stages of growth and differentiation. Prolactin (PRL) produced no detectable effect on M1 gastric mucin secretion in HT-29 cells adapted to methotrexate (HT-29-MTX) or on acid secretion in isolated rabbit parietal cells. GHRd3, an isoform of human GHR transcript missing exon 3, was also broadly expressed and was the only form found in gastric and colorectal adenocarcinomas. Interestingly, several extra bands of polymerase chain reaction products of the human PRLR, which were smaller than the expected size, were observed not only in the GI tract but also in liver and T-47D breast cancer cells. These products from human intestinal and breast cancer cell lines were subsequently subcloned and sequenced, and we isolated six isoforms of the receptor transcripts. One of these clones encodes a putative human PRL binding protein. The expression of PRL and PRLR transcripts was also clearly observed in intraepithelial lymphocytes purified from the mouse intestine. The widespread expression of the PRL and GH receptor transcripts in gastric and intestinal mucosal lineages, particularly in epithelia, suggests regulatory roles of these hormones on digestive and immune functions, including metabolism, growth, or differentiation.

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TL;DR: A clear picture of how the influence of neuroendocrine hormones may be used to favorably alter pathophysiologic processes affecting immune function and development is not yet clear.

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TL;DR: Data indicate that rMCH may act as a central corticotropin inhibitory factor involved in the circadian rhythmicity of plasma ACTH levels and that NEI antagonizes its action.
Abstract: The physiological role of melanin-concentrating hormone (MCH) in mammals is still very elusive, but this peptide might participate in the central control of the hypothalamopituitary adrenal (HPA) axis during adaptation to stress. Cloning and sequencing of the rat MCH (rMCH) cDNA revealed the existence of additional peptides encoded into the MCH precursor. Among these peptides, neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) is co-processed and secreted with MCH in rat hypothalamus. In the present work we examined: (1) The pattern of rMCH mRNA expression during the light and dark conditions in the rat hypothalamus and (2) The effect of intracerebroventricular (ICV) injections of rMCH and NEI in the control of basal or ether stress-modified release of corticotropin (ACTH), prolactin (PRL) and growth hormone (GH) secretion in vivo in light-on and light-off conditions. Our data indicate that rMCH mRNA levels do not change during the light-on period, but increase after the onset of darkness. Either alone or co-administered, rMCH and NEI do not modify basal secretion of GH and PRL at any time tested nor do they alter ether stress-induced changes in these two hormonal secretions. At the end of the light on period corresponding to the peak of the circadian rhythm in ACTH, administration of rMCH but not NEI leads to a decrease in ACTH levels while MCH is not effective during the light off period of the cycle (i.e. when basal ACTH levels are already low). Using a moderate ether induced stress, ACTH levels are only stimulated during the dark phase of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

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TL;DR: The present results suggest that the growth hormone response and the hypothermic response to the intravenous infusion of flesinoxan may serve as a valid index of 5-HT1A receptor function in humans.

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TL;DR: The observed effect of CRF on stromal cells and on prolactin release was significantly augmented by the coincubation in the presence of medroxyprogesterone acetate, indicating CRF as a novel factor of decidualization and confirming that progestins act as enhancers of the expression ofDecidual products.

Journal ArticleDOI
TL;DR: Findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypog onadotropic hypogonadism.
Abstract: Summary Male epileptic patients frequently complain of sexual dysfunction, particularly impotence and loss of libido. Epilepsy itself, antiepileptic drugs (AEDs), and psychosocial factors are believed to contribute to impaired sexuality. We studied luteinizing hormone (LH) ulsatile secretion, gonadotropin, and prolactin (PRL) esponses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) in 37 adult male epileptic patients receiving AED monotherapy who were seizure-free and had normal EEGs. Sexuality was assessed by psychological interview. Impotence was diagnosed in 8 patients (in 2 combined with loss of sexual desire). The occurrence of hyposexuality (-20%) was independent of epilepsy syndrome or AED. No change in total testosterone (T) level was observed. Free T (ft)and dihydrotestosterone (DHT) levels were lower and sex hormone binding globulin (SHBG) levels were higher in epileptic subjects than in healthy controls, but a statistically significant difference was not observed between hypo- and normosexual patients. In impotent epileptic patients, estradiol (E2) levels were significantly increased as compared with those of patients with preserved sexuality and of healthy controls. The unbalanced relation between androgen and E2 levels was emphasized by decreased fT/E2, fT/E2, and DHT/E2 ratios obtained in hyposexual epileptic patients. In this group, LHRH induced blunted LH peaks. No changes were noted in LH pulsatility features. These findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypogonadotropic hypogonadism.