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Showing papers on "Prolactin published in 1992"


01 Jan 1992
TL;DR: Basal and post-stimulation prolactin levels were correlated with estradiol levels and the hypothesis that central dopaminergic inhibition is related to diminished LH release in this state of anorexia nervosa was supported.
Abstract: To evaluate the possible role of central dopaminergic suppression of gonadotropin secretion in the genesis of amenorrhea associated with anorexia nervosa (A.N.), a central D-2 dopamine receptor blocker was administered to 10 women with A.N. and 10 regularly menstruating age-matched controls. Serum prolactin and luteinizing hormone (LH) levels were measured at -15, 0, 30, 60, 120, and 180 min after administration of metoclopramide (10 mg orally). Mean basal prolactin t?~ C 0.001) and estradiol levels @ c 0.02) were significantly lower in women with A.N. The prolactin response to metoclopramide was significantly impaired in women with anorexia nervosa. No correlation was found between the prolactin response and percentage ideal body weight. Basal and post-stimulation prolactin levels were correlated with estradiol levels. After adjusting for the effects of estradiol, significant differences between patients with A.N. and controls remained in prolactin levels at baseline (p < 0.011, 120 min tp C 0.02) and 150 min ()I < 0.05). Metoclopramide did not induce a significant rise in LH levels in either the A.N. or control groups. These data are consistent with central dopaminergic inhibition of prolactin secretion in anorexia nervosa but do not support the hypothesis that central dopaminergic inhibition is related to diminished LH release in this state.

700 citations


Journal ArticleDOI
21 Aug 1992-Science
TL;DR: The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotroPE, and thyrotrope cell types.
Abstract: A point mutation in the POU-specific portion of the human gene that encodes the tissuespecific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative α helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elments but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.

439 citations


Journal ArticleDOI
21 Aug 1992-Science
TL;DR: A point mutation in the gene encoding Pit-1 was identified on one allele in a patient with combined pituitary hormone deficiency in two dwarf mouse strains displaying hypoplasia of growth hormone, prolactin, and thyroid-stimulating, hormonesecreting cell types as discussed by the authors.
Abstract: Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Mutations in the gene encoding Pit-1 have been found in two dwarf mouse strains displaying hypoplasia of growth hormone, prolactin, and thyroid-stimulating, hormone-secreting cell types in the anterior pituitary. A point mutation in this gene was identified on one allele in a patient with combined pituitary hormone deficiency. Mutant Pit-1 binds DNA normally but acts as a dominant inhibitor of Pit-1 action in the pituitary.

437 citations


Journal ArticleDOI
TL;DR: An entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the Pit-1/GHF-1, the first report in humans of a defect in a transcription activator causing deficiency of multiple target genes.
Abstract: Cretinism is marked by irreversible mental and growth retardation. We describe here an entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the pituitary specific transcription activator, Pit-1/GHF-1 (designated PIT1 in humans for pituitary specific factor 1). This is the first report in humans of a defect in a transcription activator causing deficiency of multiple target genes.

312 citations


Book
01 Jan 1992
TL;DR: The role of growth hormone in the growth of poikilotherms and homeotherms, and the role of prolactin and placental lactogens in vertebrate growth and development, is investigated.
Abstract: Introduction, R. De Pablo. Part 1 Growth hormone and prolactin: evolution of the structure of the growth hormone and prolactin family, M. Rand-Weaver, et al the role of growth hormone in the growth of poikilotherms, E. McLean and E.M. Donaldson role of growth in hormone growth of homeo-therms, N.C. Steele and C.M. Evock-Clover growth hormone and metabolism, H.M. Goodman the growth hormone receptor and growth hormone-binding protein - structure, functions, and regulation, S.D. Cramer and F. Talamantes growth hormone secretion in poikilotherms and homeotherms, S. Harvey role of prolactin and placental lactogens in vertebrate growth and development, C.S. Nicoll. Part 2 Insulin, insulin-like growth factors, growth factors: insulin-like growth factors - role in growth and development, T.D. Etherton non-IGF growth factors that mediate cell proliferation and differentiation, A.L. Johnson insulin and growth, J.P. McMurtry pancreatic hormones and metabolism, R.L. Hazelwood adrenomedullary catecholamines, A. Epple beta adrenergic agonists and growth, D.H. Beerman glucocorticoids - metabolism, growth and development, C.B. Schreck thyroid hormone effects on growth, development and metabolism, A. McNabb and D.B. King hormones and skeletal growth, S. Hurwitz and M. Pines hormones involved in regulation of muscle differentiation and growth, G. Goldspink and E. Hansen hormones and adipose growth, D.J. Flint and R.G. Vernon endocrine regulation of the growth and development of warm-blood vertebrate embryos and fetuses, R.C. Thommes and J.E. Woods hormones metamorphosis and smolting, W.W. Dickhoff manipulation of animal growth, C.G. Scanes and C. Baile evolution of growth-related hormones and factors - the insulin/insulin-like growth family, C.G. Scanes and Robert M. Campbell.

263 citations


Journal ArticleDOI
TL;DR: It is concluded that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation.
Abstract: Prolactin has been shown to have an immunoregulatory role in the rodent immune response. A prolactin-like molecule has also been found in mouse splenocytes and a human B-lymphoblastoid cell line. We have evaluated whether human peripheral blood mononuclear cells (PBMCs) synthesize and/or secrete prolactin. We used the polymerase chain reaction (PCR) to generate a 276-base-pair prolactin product from human PBMCs, and Southern blot analysis confirmed that it was related to prolactin. Western blotting using a polyclonal antibody to prolactin indicated that cell extracts prepared from human PBMCs contained a high molecular mass (60-kDa) immunoreactive prolactin. To determine whether this PBMC prolactin was being secreted, we developed a highly sensitive and specific hormonal enzyme-linked immunoplaque assay. With this assay, we were able to detect human prolactin secretion from concanavalin A (Con A)- or phytohemagglutinin-stimulated PBMCs but not from unstimulated PBMCs. We next sought to determine whether this secreted prolactin could function as an autocrine growth factor in lymphoproliferation. We observed that anti-human prolactin antiserum significantly inhibited human PBMC proliferation in response to Con A or phytohemagglutinin. We conclude that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation.

215 citations


Journal ArticleDOI
TL;DR: Three point mutations in the Pit-1 gene are identified, Pro24Leu, Arg143Gln, and Arg271Trp, located on the major transactivation region, POU-specific domain, and Pou-homeodomain, respectively.

165 citations


Journal ArticleDOI
TL;DR: The novel hypothalamic peptide pituitary adenylate cyclase-activating polypeptide (PACAP-38) caused an increase in the release of GH, ACTH, LH and alpha-subunit and accumulation of intracellular cyclic AMP from dispersed rat anterior pituitsary cells in static culture for 24 h.
Abstract: We have demonstrated that the novel hypothalamic peptide pituitary adenylate cyclase-activating polypeptide (PACAP-38; 0.1-100 nmol/l) caused an increase in the release of GH, ACTH, LH and alpha-subunit and accumulation of intracellular cyclic AMP from dispersed rat anterior pituitary cells in static culture for 24 h. There were no significant effects on TSH or prolactin release over the same time-period. PACAP-38 (10 nmol/l) increased the release of GH by 1.3-fold (P less than 0.05), ACTH by 1.9-fold (P less than 0.05), LH by 3.5-fold (P less than 0.001) and alpha-subunit by 2.0-fold (P less than 0.005) and the accumulation of intracellular cyclic AMP by greater than 2-fold (P less than 0.001) after 24 h. However, the time-course for the effect of PACAP-38 (1 mmol/l) on hormone release and intracellular cyclic AMP levels showed a temporal dissociation. The effect of PACAP-38 on GH and ACTH levels did not reach significance until 24 h whereas the effect of PACAP-38 on LH and alpha-subunit release reached significance after 4 h implying a different mechanism of action for their release. To investigate the PACAP-induced secretion of LH and alpha-subunit further, we examined the effects of PACAP after down-regulation of protein kinase C (PKC). PACAP-38 at a dose maximal for the stimulation of LH and alpha-subunit release (10 nmol/l) added together with the PKC activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 0.1 mumol/l) had no greater effect on LH and alpha-subunit release than TPA alone over a 4 h incubation period.(ABSTRACT TRUNCATED AT 250 WORDS)

144 citations


Journal ArticleDOI
TL;DR: The finding of testosterone stimulation of brain PRL message and undetectable levels of Pit-1 (GHF-1) in hypothalamic and extrahypothalamic brain regions indicates that the transcriptional regulation of PRL in the brain is different from that in the anterior pituitary.
Abstract: Previous work by our laboratory has described the presence and widespread distribution of a PRL-like immunoreactive protein in brain. The persistence of this PRL in brain after hypophysectomy provided substantial evidence that brain PRL represented the product of a synthetic pool separate from that of the anterior pituitary PRL. To pursue this concept of independent synthesis further, we sought to determine whether brain tissue expressed PRL mRNA. Although we were easily able to detect a single species of PRL mRNA in pituitary by Northern hybridization, we could not visualize message in hypothalamus or extrahypothalamic brain by this technique. Therefore, we performed the polymerase chain reaction on cDNAs from anterior pituitary, hypothalamus, discrete extrahypothalamic brain regions, and other tissues. Hypothalamus and extrahypothalamic brain parts, including the cerebellum, caudate, brain stem, amygdala, thalamus, cortex, and hippocampus, were all positive to varying degrees. Lung and liver were negative, and anterior pituitary was consistently positive. All positive tissues, including anterior pituitary, expressed two hybridization signals: the expected amplified product and another smaller one. The smaller amplified product is presumably the result of an alternatively spliced transcript that is missing part of the PRL gene. Hypophysectomized animals did not express PRL message in brain, but expression was restored in hypophysectomized animals treated with testosterone. Transcripts for Pit-1 (GHF-1), a transcription factor important in regulation of pituitary PRL, were not detected in hypothalamus or any of the extrahypothalamic brain parts. The finding of testosterone stimulation of brain PRL message and undetectable levels of Pit-1 (GHF-1) in hypothalamic and extrahypothalamic brain regions indicates that the transcriptional regulation of PRL in the brain is different from that in the anterior pituitary.

139 citations


Journal ArticleDOI
TL;DR: It is concluded that physical training causes adaptive changes in highly trained runners so that identical GH and PRL responses to exercise are recorded at higher absolute workloads.
Abstract: The effect of acute exercise at three graded intensities on plasma growth hormone (GH) and prolactin (PRL) concentrations was examined in three groups of healthy male volunteers. According to their tr

137 citations


Journal ArticleDOI
TL;DR: It is likely that a seasonal pattern of prolactin secretion is only evidence of neuroendocrine sensitivity to changing photoperiod, and this sensitivity to the seasonal changes in daylength may or may not be accompanied by seasonalChanges in a biological endpoint such as seasonal reproduction or indeed other adaptations.
Abstract: The majority of seasonally breeding mammals show a seasonal pattern of prolactin secretion with peak concentrations in spring or summer and a nadir in autumn or winter. Photoperiod influences prolactin secretion via its effects on the secretion of the pineal hormone melatonin. Preliminary evidence suggests that the effects of melatonin on both prolactin and gonadotrophin secretion are via a common target area, possibly within the anterior hypothalamus, and that differences in response to photoperiod may be due to differences in the processing and/or interpretation of the melatonin signal. In contrast to seasonal gonadotrophin secretion, the seasonal changes in prolactin are not due to changes in the sensitivity of a feedback loop and so must be due to direct effects on the hypothalamic pathways that control prolactin secretion. Little else can be said with confidence about the neuroendocrine mechanisms that lead to the seasonal changes in prolactin secretion. Dopamine and noradrenaline turnover in the arcuate nucleus and median eminence decrease under short daylength. If catecholamine turnover in these structures is positively correlated with catecholamine concentrations in the long or short hypophysial portal vessels, it is unlikely that the decrease in prolactin concentration in winter is due to the effects of increased concentrations of dopamine or noradrenaline in the portal vessels. There is, however, evidence for increased pituitary sensitivity to dopamine under short daylength, so increased dopamine concentrations may not be required for suppression of prolactin secretion at this time. In addition to the diminished secretion of prolactin under short daylength, rate of prolactin synthesis and pituitary content of prolactin also decline although the mechanisms that regulate these changes are poorly understood. Although all seasonal breeders show a seasonal change in prolactin secretion, there are continuously breeding species in which prolactin secretion is also under photoperiodic control. It is likely therefore that a seasonal pattern of prolactin secretion is only evidence of neuroendocrine sensitivity to changing photoperiod. Depending upon the species, this sensitivity to the seasonal changes in daylength may or may not be accompanied by seasonal changes in a biological endpoint such as seasonal reproduction or indeed other adaptations. Whether the seasonal change in prolactin secretion is an endocrine mediator of such adaptations remains in contention. Certainly in some species this signal does have a role in reproduction. For example, in species with an obligate seasonal embryonic diapause, the seasonal increase in prolactin can act as a luteotrophin (mink and western spotted skunk) or luteostatin (Bennett's and tammar wallabies.(ABSTRACT TRUNCATED AT 400 WORDS)

Journal ArticleDOI
TL;DR: Results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.

Journal Article
TL;DR: Thymic development in DW/J dwarf mice was examined and it was indicated that GH exerts significant thymopoietic effects in vivo, and peripheral T cells from dwarf mice did exhibit Ag-specific responses indicating that these mice have functional T cells.
Abstract: Growth hormone (GH) and other neuroendocrine mediators have been implicated previously in T cell development. We therefore examined thymic development in DW/J dwarf mice. DW/J mice lack acidophilic anterior pituitary cells and consequently are totally deficient in the production of GH, as well as other neuroendocrine hormones. DW/J dwarf mice had greatly hypoplastic thymi that continued to decrease in size as the mice aged. Characterization of the different T cell subpopulations within the thymi of dwarf mice indicated a deficiency in CD4+/CD8+ double-positive thymocytes. This deficiency of progenitor cells became more complete as the mice aged culminating in the total disappearance of this subpopulation in some dwarf mice > 3 mo of age. Analysis of the lymph nodes indicated that a population of double-positive (CD4/CD8) T cells appeared in some mice concurrent with the disappearance of double-positive cells in the thymus suggesting that these thymocytes may have migrated to the periphery. However, peripheral T cells from dwarf mice did exhibit Ag-specific responses indicating that these mice have functional T cells. Treatment of the mice with recombinant human GH, which binds both murine growth hormone receptors and murine prolactin receptors, or ovine GH, which binds murine growth hormone receptors but not murine prolactin receptors, resulted in an increase in thymic size and the reappearance of the CD4+/CD8+ double-positive cells within the thymus. Additionally, after GH treatment, the double-positive cells disappeared from the lymph nodes. The thymi of mice treated with GH failed to attain normal size but did develop a normal distribution of T cell progenitors. Thus, GH exerts significant thymopoietic effects in vivo. Neuroendocrine hormones may be important for normal T cell differentiation to occur within the murine thymus.

Journal ArticleDOI
TL;DR: Results indicate that approximately 50% of all the DA neurons terminating in the intermediate lobe of the rat pituitary originate in or project through the periventricular nucleus of the hypothalamus, and that these DA neurons regulate the secretion of alpha-MSH from intermediate lobe melanotrophs.
Abstract: The purpose of the present study was to provide neurochemical and endocrinological evidence that dopamine (DA) neurons terminating in the intermediate lobe of the rat pituitary originate in the periventricular nucleus of the hypothalamus. One week following surgical separation of the periventricular nucleus from the mediobasal hypothalamus, DA and 3,4-dihydroxyphenyl-acetic acid (DOPAC) concentrations in the intermediate lobe were reduced by 50%, and this was accompanied by an increase in plasma alpha-melanocyte-stimulating hormone (alpha-MSH) concentrations. In contrast, this procedure had no effect on concentrations of prolactin in the plasma, or DA or DOPAC in the median eminence, the region of the mediobasal hypothalamus containing terminals of tuberoinfundibular DA neurons. Electrical stimulation of the periventricular nucleus increased the ratio of DOPAC/DA in the intermediate lobe and reduced the concentrations of alpha-MSH in the plasma, whereas in these same animals the DOPAC/DA ratio in the median eminence and concentrations of prolactin in the plasma were unaltered. These results indicate that approximately 50% of all the DA neurons terminating in the intermediate lobe of the rat pituitary originate in or project through the periventricular nucleus of the hypothalamus, and that these DA neurons regulate the secretion of alpha-MSH from intermediate lobe melanotrophs.

Journal ArticleDOI
TL;DR: A regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene is identified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotsrope lineage and is not Pit-1/GHF-1.
Abstract: The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.

Journal ArticleDOI
TL;DR: Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females, suggesting the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients.
Abstract: OBJECTIVES Dopamine is currently used in the ICU for its vasopressor, renal vasodilating, and cardiac inotropic properties. Animal studies have shown both endocrine and T-lymphocyte alterations with dopamine agonist administration. The relationships between exogenous dopamine and patient hormonal and lymphocyte proliferative responses have not been evaluated in the critically ill patient. These findings furnished the impetus for the present study. DESIGN Prospective, controlled, clinical study. PATIENTS AND METHODS All patients admitted to the ICU at Truman Medical Center were evaluated for admission into the protocol, excluding patients whose medications or diseases produced effects in the study-dependent variables. Before institution of dopamine therapy, blood samples were taken for T-cell analysis and prolactin measurement. Daily, early morning blood samples were taken if the dopamine infusion was > 5 micrograms/kg/min for 4 hrs during that 24-hr period. An early morning postdopamine sample was taken on the first day after dosage discontinuation. Control blood samples for determination of T-cell and prolactin responses were drawn from ICU patients who did not receive dopamine. A severity-of-disease score (Acute Physiology and Chronic Health Evaluation [APACHE II] score) was recorded for all patients. MAIN RESULTS Serum prolactin concentrations decreased > 90% (p < .001) within hours in all patients receiving dopamine infusions at study dose limit or above. The in vitro T-cell proliferative response to concanavalin A decreased (a transitory response) in patients receiving a dopamine infusion (p < .001). Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females. An immediate transitory decrease in patient T-cell response to concanavalin A stimulation in vitro was seen in patients receiving dopamine. CONCLUSIONS The data suggest the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients.

Journal ArticleDOI
TL;DR: Recent clinical and laboratory data suggest that the commonly used antiestrogen tamoxifen also acts to reduce serum IGF-I levels, which may contribute to the cytostatic activity of the drug.
Abstract: Antiestrogens are widely used in the management of hormonally responsive breast cancer in both adjuvant and palliative settings, and are currently being evaluated as chemopreventive agents The classical mechanism of action of these drugs involves inhibition of estrogen-stimulated neoplastic cell proliferation by blockade of estrogen receptors present on breast cancer cells This paper reviews recent clinical and laboratory data that suggest that the commonly used antiestrogen tamoxifen also acts to reduce serum IGF-I levels Estrogens appear to play a permissive role in growth hormone (GH) release by the pituitary gland and GH is known to stimulate IGF-I expression by hepatocytes It is therefore possible that blockade of estrogen receptors in the hypothalamic-pituitary axis by tamoxifen interferes with GH release, leading to reduced hepatic IGF-I expression In view of results suggesting that IGF-I is a more potent mitogen than estradiol for breast cancer cells and data demonstrating a positive correlation between estrogen receptor level and IGF-I receptor level of breast cancer cells, the IGF-I lowering effect of tamoxifen may contribute to the cytostatic activity of the drug The interrelationships between steroid hormone physiology and IGF-I physiology may have relevance to a variety of commonly used treatments for hormonally responsive cancers

Journal ArticleDOI
TL;DR: Examination of the distribution of prolactin and growth hormone receptor transcripts at mid-pregnancy by semi-quantitative reverse transcriptase polymerase chain reaction showed that both are widespread in bovine fetal and placental tissues.

Journal ArticleDOI
TL;DR: Following cabergoline discontinuation, prolactin levels increased slowly, being still markedly lower than pretreatment values after three months; 10 patients out of 32 had persistently normal prolACTin levels during one year of follow-up.
Abstract: The efficacy and safety of the new long-acting dopamine agonist cabergoline were evaluated in 127 hyperprolactinemic patients (124F and 3M; 71 with microprolactinoma, 14 with macroprolactinoma, 5 with operated macroprolactinoma and 37 with idiopathic disorder) who were treated with the drug for from 3 to 52 months (median, 14 months). Cabergoline was administered orally at dose levels ranging between 0.2 and 3.5 mg per week, given once weekly in 92 patients, twice weekly in 22, thrice weekly in 9 and daily in 4. Serum prolactin and progesterone levels, hematology, blood chemistry and electrocardiograms were frequently evaluated throughout treatment. CT or MR imaging of the pituitary was repeated during treatment in patients with macroprolactinoma and in 38 with microprolactinoma. After drug discontinuation, serum prolactin and gonadal function were evaluated monthly for three months in 65 patients and for up to two years in 12. Serum prolactin levels were normalized in 114 patients (90%). Of 56 women with amenorrhea, 52 resumed menses (with presumptive evidence of ovulation in 49); 17 women became pregnant; and sexual potency was restored in the 3 men. Evidence of tumor shrinkage was obtained in 13 of the 14 patients with macroprolactinoma and in 28 of 38 with microprolactinoma; complete disappearance of the tumor image was achieved in 2 macro and 14 microprolactinomas. A total of 48 adverse events was reported by 29 patients (23%), almost all typical of the pharmacological class and mild to moderate; no patient withdrew from treatment due to adverse events. Safety parameters did not change. Following cabergoline discontinuation, prolactin levels increased slowly, being still markedly lower than pretreatment values after three months; 10 patients out of 32 had persistently normal prolactin levels during one year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The data suggest that TGF-beta 1 is produced in the pituitary gland and inhibits the secretion of PRL and growth of lactotropes in an autocrine and/or paracrine fashion.
Abstract: Transforming growth factor-beta 1 (TGF-beta 1) is known to inhibit cell growth and proliferation of many estrogen-responsive normal and transformed cells. The effect of this polypeptide growth factor on the estrogen-responsive pituitary lactotropes has not been determined. To evaluate the role of TGF-beta 1 in the control of lactotropic growth, the action and production of TGF-beta 1 in the anterior pituitary was studied in rats. The growth factor suppressed basal PRL release from the primary culture of enriched rat lactotropes in a concentration-dependent manner in the range of 2 pg/ml-20 ng/ml. The growth factor did not affect the secretion of other pituitary hormones in the cultures. The inhibitory action of TGF-beta 1 on PRL release was time dependent. The minimum time required to produce a significant effect was 4 h. The growth factor also suppressed estradiol-induced PRL release as well as it inhibited estradiol-induced proliferation of lactotropes. TGF-beta 1 immunoreactivity was detected in the ce...

Journal ArticleDOI
TL;DR: It is concluded that, in dogs, luteal regression occurs independently of a uterine luteolysin, but that the uterus may play a role in control of duration of anoestrus, and Pseudopregnancy seems to be initiated by a fall in progesterone concentrations rather than by other hormonal changes.
Abstract: In studies of five hysterectomized and five control dogs, hysterectomy shortened the anoestrous interval (96.6 +/- 28.0 versus 149.4 +/- 50.9 days, P < 0.05). No differences in hormone concentrations (progesterone, oestradiol, prolactin and growth hormone) were observed between the control and hysterectomized dogs except for a brief fall in progesterone concentrations over 8 days immediately after surgery, between days 35 and 40 after onset of pro-oestrous bleeding; only these animals developed symptoms of overt pseudopregnancy. It is concluded that, in dogs, luteal regression occurs independently of a uterine luteolysin, but that the uterus may play a role in control of duration of anoestrus. Pseudopregnancy seems to be initiated by a fall in progesterone concentrations rather than by other hormonal changes.

Journal ArticleDOI
TL;DR: Data show that in vivo administration of two closely related pituitary hormones, GH and prolactin, can effectively prime macrophages, which is consistent with the hypothesis that GH mediates resistance to S. typhimurium by a direct stimulatory action on Macrophages.
Abstract: Purified and recombinant forms of growth hormone (GH) as well as of recombinant rat gamma interferon (IFN-gamma) enhance the survival of rats deprived of endogenous pituitary GH secretion by hypophysectomy (HX rats) and infected with virulent Salmonella typhimurium. Macrophages obtained from rats with intact pituitaries (pituitary-intact rats) or HX rats that were treated in vivo with either GH or the closely related hormone prolactin released elevated (P less than 0.05) levels of superoxide anion (O2-) after in vitro opsonized-zymosan stimulation compared with those from placebo-treated animals. These levels of O2- release were similar in magnitude to those of macrophages from rats treated in vivo with IFN-gamma. In time course in vivo macrophage activation studies, both IFN-gamma and GH significantly increased O2- secretion within 24 h, with maximal secretion occurring at day 3. Macrophages obtained from pituitary-intact and HX rats injected in vivo with GH also released elevated (P less than 0.05) levels of hydrogen peroxide (H2O2) and displayed enhanced (P less than 0.01) phagocytic activity toward opsonized Listeria monocytogenes in vitro. The mechanism of action of GH in vivo is likely to be a direct one because resident peritoneal macrophages from rats could be primed in vitro for enhanced secretion of O2- following triggering of these cells with opsonized zymosan. These data show that in vivo administration of two closely related pituitary hormones, GH and prolactin, can effectively prime macrophages, which is consistent with the hypothesis that GH mediates resistance to S. typhimurium by a direct stimulatory action on macrophages.

Journal ArticleDOI
TL;DR: A double-faceted regulatory role of this hormone in vivo is shown, in addition to triggering resting lymphocytes to cell division, the hormone can also control the magnitude of their response to polyclonal stimuli.
Abstract: Prolactin (PRL) has been shown to contribute to the development of lymphoid tissues and maintenance of physiological immune function. Here we show that the role of the hormone extends to the control of the effector phase of the immune response. In addition to triggering resting lymphocytes to cell division, the hormone can also control the magnitude of their response to polyclonal stimuli. Concentrations of PRL in the physiological range increased the [3H]thymidine, [3H]uridine, and [3H]leucine incorporation of unstimulated NK cells cultured in serum-free conditions. The same concentrations of the hormone increased the response of NK, T, and B cells to the mitogenic stimuli interleukin 2 (IL2), phytohemagglutinin (PHA), and staphylococcus aureus cowan, respectively, the effect being maximally evident in the presence of suboptimal concentrations of the mitogens. By contrast concentrations of PRL five- to tenfold the physiological levels inhibited the mitogenic response to IL2 and PHA. These data indicate a double-faceted regulatory role of this hormone in vivo.

Journal ArticleDOI
TL;DR: A co-ordinated series of changes to reduce lipid synthesis in the mammary gland and enhance lipogenesis and triglyceride storage in adipose tissue of animals given the combined treatment of bromocriptine and anti-rGH was represented.
Abstract: Inhibition of prolactin secretion with bromocriptine and neutralization of GH action with a specific antiserum to rat GH (rGH) were used to explore the modes of action of GH and prolactin in maintaining lactation in the rat. Treatment of dams with anti-rGH caused a small reduction in litter weight gain whilst bromocriptine reduced litter weight gain by 50%. When both treatments were combined, however, milk yield ceased completely and this was accompanied by a wide variety of effects on mammary lipid metabolism including decreases in the mRNA concentrations of acetyl CoA carboxylase, fatty acid synthase, malic enzyme and lipoprotein lipase. Activities of acetyl CoA carboxylase and lipoprotein lipase were also significantly reduced. Reciprocal changes were evident in adipose tissue with increases in acetyl CoA carboxylase and lipoprotein lipase activities. In conjunction with a decreased lipolytic response to noradrenaline in adipose tissue of animals given the combined treatment of bromocriptine and anti-rGH, this represented a co-ordinated series of changes to reduce lipid synthesis in the mammary gland and enhance lipogenesis and triglyceride storage in adipose tissue as milk production ceased. All of these effects could be prevented in part by concurrent treatment with GH, but insulin-like growth factor-I (IGF-I) and IGF-II failed to affect any of the parameters measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: While there was a significant increase in cortisol, prolactin and TSH levels after both jumps, no alterations could be observed in STH and LH levels.

Journal ArticleDOI
TL;DR: The present studies were designed to test the hypothesis that phosphorylation is an important modulator of Pit-1 interaction with the TSH beta gene, and may limit basal activation of the T SH beta gene by binding less well to nonphosphorylated Pit- 1 while conferring hormonal stimulation through enhanced binding of phosphorylatedpituitary.
Abstract: The pituitary-specific transcription factor Pit-1 is a cell-specific activator of prolactin and growth hormone gene transcription in the anterior pituitary. Pit-1 has also been shown to mediate both thyrotropin-releasing hormone (TRH) and cAMP stimulation of the prolactin and thyrotropin beta-subunit (TSH beta) genes. The molecular mechanism by which Pit-1 mediates these stimulatory effects remains unclear. At least three Pit-1-binding elements within the TSH beta gene mediate responsiveness to TRH and cAMP. The present studies were designed to test the hypothesis that phosphorylation is an important modulator of Pit-1 interaction with the TSH beta gene. TSH beta elements bind less well to nonphosphorylated Pit-1 than to phosphorylated Pit-1 and are weak activators of gene expression, unlike high-affinity Pit-1 binding sites in the prolactin and growth hormone genes. Phosphorylation by protein kinase A or C enhances Pit-1 binding to TSH beta elements 3- to 8-fold. Conversely, phosphorylation generally reduces binding of Pit-1 to elements within the prolactin and growth hormone genes. A variation within the consensus sequence for Pit-1 binding in TSH beta gene elements [A(A/T)(A/T)AATNCAT in the TSH beta gene versus A(A/T)(A/T)TATNCAT in the prolactin and growth hormone genes] could explain these differences. These elements may limit basal activation of the TSH beta gene by binding less well to nonphosphorylated Pit-1 while conferring hormonal stimulation through enhanced binding of phosphorylated Pit-1.

Journal Article
TL;DR: Antipsychotic drugs are the psychotropic agents most likely to cause symptomatic hyperprolactinemia and bromocriptine or amantadine may provide symptomatic relief if withdrawal or adjustment of the antipsychotic dosage does not eliminate the symptoms.
Abstract: The effects of individual psychotropic medications on serum prolactin concentrations are described, and recommendations for dealing with adverse effects are provided. Hyperprolactinemia can result in galactorrhea, amenorrhea, irregular menses, and anovulation; in men, impotence and azoospermia, with or without lactation and gynecomastia, can occur. Antipsychotics may block dopamine receptors in the pituitary prolactin-secreting cells and prevent dopamine-induced reduction of prolactin release. The magnitude of the increase in prolactin concentration correlates with the amount of antipsychotic drug given. The treatment of choice is reduction of the antipsychotic dosage or discontinuation of therapy. If adjustments to the antipsychotic dosage fail to resolve symptoms, the dopamine agonists bromocriptine and amantadine may be tried. Antidepressants may produce elevated serum prolactin concentrations, especially with long-term administration. However, the frequency of antidepressant-induced hyperprolactinemia is much lower than that seen with antipsychotics, and serious adverse clinical effects are uncommon. Other psychotropic drugs such as lithium, valproic acid, buspirone, carbamazepine, and benzodiazepines either are only rarely associated with symptomatic hyperprolactinemia or do not produce clinically important changes in prolactin concentrations. Antipsychotic drugs are the psychotropic agents most likely to cause symptomatic hyperprolactinemia. Bromocriptine or amantadine may provide symptomatic relief if withdrawal or adjustment of the antipsychotic dosage does not eliminate the symptoms.

Journal ArticleDOI
TL;DR: The data suggest that PRL may feed back at the level of the hypothalamus and pituitary gland through the same short and/or long PRL-R mRNA that mediate PRL action in the peripheral tissues.
Abstract: Prolactin receptor (PRL-R) mRNAs exist in several tissues where prolactin is known to act including the liver, testes, prostate, ovary, mammary gland, adrenal gland and kidney. PRL also acts at the level of the hypothalamus and pituitary gland to feed back and regulate its own secretion and the secretion of other anterior pituitary hormones. Therefore, we hypothesized that PRL-R mRNA would exist in these target tissues as well. Total RNA was extracted from rat anterior and medial basal hypothalamus, anterior and posterior pituitary gland, cerebral cortex, skeletal muscle and liver. After reverse transcribing total RNA with Murine-MLV reverse transcriptase and random or oligo(dT) pmers, the polymerase chain reaction (PCR) was performed. PCR products were then analyzed by ethidium bromide staining. Using primers that flanked the coding region for the extracellular binding domain we detected PRL-R mRNA in the anterior and medial basal hypothalamus, anterior and posterior pituitary gland, as well as in the li...

Journal ArticleDOI
TL;DR: It appears that, when PRL is secreted in excess during pregnancy, somatotrophs are recruited to produce PRL, and it is demonstrated that GH is stored following discontinuation of GH synthesis.
Abstract: Lactotroph hyperplasia is a prominent finding in the adenohypophyses of pregnant women. In order to elucidate the morphogenesis of this change, pituitaries from 16 women in various phases of pregnancy were collected at autopsy and studied by histology, immunocytochemistry and in situ hybridization. The results showed that the increase in the amount of prolactin (PRL) mRNA paralleled the progressive lactotroph hyperplasia. The presence of mitoses in PRL-immunoreactive cells provided evidence that proliferation of preexisting lactotrophs contribute to lactotroph accumulation. Growth hormone (GH) immunoreactive cells showed a marked reduction in GH mRNA indicating that GH synthesis was inhibited. In many GH-immunoreactive cells, PRL mRNA became apparent. These findings demonstrate that GH is stored following discontinuation of GH synthesis. It appears that, when PRL is secreted in excess during pregnancy, somatotrophs are recruited to produce PRL. These somatotrophs begin to express PRL mRNA, transform to bihormonal mammosomatotrophs and possibly later to lactotrophs, contributing to PRL production. Mature somatotrophs may be regarded as reserve cells in the adenohypophysis, having the potential to switch hormone synthesis and to convert to mammosomatotrophs and possibly lactotrophs.

Journal ArticleDOI
TL;DR: Spleen cells showed an enhanced mitogen response to immobilization and adrenalectomy, indicating that the immune response is differently regulated in the various compartments of the immune system.
Abstract: The effects of short-term handling and different durations of immobilization on serum levels of catecholamines, ACTH, prolactin, and corticosterone and in vitro functions of lymphocytes were examined in rats. The results show that changes in the immune response of peripheral blood lymphocytes (PBL) depend on the intensity of the stressor: Short (1 min) handling of cannulated rats induced an enhanced stimulation of PBL to respond to T and B cell mitogens, whereas immobilization of the same animals led to suppression, dependent on the time this stressor was applied. The decrease in the mitogen reactivity of PBL after 120 min of immobilization was reversible within 24 h, and could be largely prevented by adrenalectomy, confirming that factors released by this gland are mainly responsible for immunosuppression. In contrast to PBL, spleen cells showed an enhanced mitogen response to immobilization and adrenalectomy, indicating that the immune response is differently regulated in the various compartments of the immune system. Possible correlations of the various effects with changes in stress hormone levels are discussed.