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Endocrinology Aug 2008Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however,...
Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas.
Topics: Animals; Antineoplastic Agents; Apoptosis; Bromocriptine; Cell Proliferation; Clone Cells; Curcumin; Cyclin D3; Cyclins; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Phosphorylation; Pituitary Hormones; Pituitary Neoplasms; Prolactinoma; Rats; Retinoblastoma Protein; Time Factors; Tumor Cells, Cultured
PubMed: 18450960
DOI: 10.1210/en.2007-1760 -
Pituitary Aug 2021The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and...
PURPOSE
The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated.
METHODS
In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg).
RESULTS
Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [- 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: - 0.13 [- 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (- 0.18 [- 0.22, - 0.09] mU/L, p < 0.001).
CONCLUSION
We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones.
REGISTRATION
The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.
Topics: Adrenocorticotropic Hormone; Diabetes Insipidus; Diagnostic Tests, Routine; Glycopeptides; Healthy Volunteers; Humans; Indoles; Pituitary Hormones; Prolactin; Prospective Studies; Tryptophan
PubMed: 33615399
DOI: 10.1007/s11102-021-01132-9 -
The Journal of Biological Chemistry Dec 2000N-Linked oligosaccharides terminating with the sequence SO(4)-4-GalNAcbeta1,4GlcNAcbeta1,2Manalpha are present on the pituitary hormones lutropin (LH), thyrotropin, and...
N-Linked oligosaccharides terminating with the sequence SO(4)-4-GalNAcbeta1,4GlcNAcbeta1,2Manalpha are present on the pituitary hormones lutropin (LH), thyrotropin, and pro-opiomelanocortin. The sulfated structures on LH are essential for expression of its biologic function in vivo. We have cloned the N-acetylgalactosamine-4-sulfotransferase (GalNAc-4-ST1, GenBank(TM) accession number ), which mediates sulfate addition to the N-linked oligosaccharides on LH and other pituitary glycoproteins with terminal (beta1,4-linked GalNAc based on its homology to HNK-1 sulfotransferase (HNK-1 ST). GalNAc-4-ST1 displays 23% identity to HNK-1 ST and 28% to chondroitin 4-sulfotransferase 1 (C4ST-1) and 26% to chondroitin 4-sulfotransferase 2 (C4ST-2). The cDNA predicts a type II transmembrane protein of 424 amino acids with four potential N-linked glycosylation sites and a single membrane-spanning domain. GalNAc-4-ST1 has putative 5'-phosphosulfonate and 3'-phosphate binding sites. Three more carboxyl-terminal regions of unknown function also show a high degree of identity with HNK-1 ST, C4ST-1, and C4ST-2. The membrane-bound form of GalNAc-4-ST1 transfers sulfate to GalNAcbeta1, 4GlcNAcbeta-R but not to chondroitin, whereas truncated forms of GalNAc-4-ST1 that are released into the medium transfer sulfate to both GalNAcbeta1,4GlcNAcbeta-R and chondroitin. The first 118 amino acids of GalNAc-4-ST1 appear to contribute to both its activity and specificity for terminal beta1,4-linked GalNAc. GalNAc-4-ST1 also efficiently transfers sulfate to N-linked oligosaccharides on native LH and other glycoproteins terminating with beta1,4-linked GalNAc. A single transcript of 2.4 kilobases is most highly expressed in the pituitary and other regions of the central nervous system. The GalNAc-4-ST1 gene is located on human chromosome 19q13.1.
Topics: Amino Acid Sequence; Animals; Base Sequence; CHO Cells; Carbohydrate Sequence; Chromosome Mapping; Chromosomes, Human, Pair 19; Cloning, Molecular; Cricetinae; Humans; Luteinizing Hormone; Molecular Sequence Data; Oligosaccharides; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Rats; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Sulfotransferases; Thyrotropin; Transfection
PubMed: 10988300
DOI: 10.1074/jbc.M007821200 -
Journal of Physiology and Pharmacology... Mar 2009Cortistatin (CST), a novel neuropeptide, shows high structural homology and functional resemblance with somatostatin. CST binds with high affinity to all somatostatin... (Comparative Study)
Comparative Study
Cortistatin (CST), a novel neuropeptide, shows high structural homology and functional resemblance with somatostatin. CST binds with high affinity to all somatostatin receptors, and contrary to somatostatin, is also able to bind with MrgX2 and GH secretagogue receptor of ghrelin (GHS-R1) receptors. The aim of the present investigation was to evaluate in vivo the effect of peripheral administration of cortistatin on pituitary hormone release in comparison with somatostatin (SS) treatment. Adult male rats used in the experiment, were given peripheral injection of cortistatin, somatostatin or vehicle. Blood was withdrawn 60 and 120 minutes thereafter. We found short lasting significant decrease of GH concentration as a result of administration of CST and SS when compared with saline injected controls. Prolactin levels were increased 60 min after cortistatin but not to somatostatin injection. There was no effect of CST on both LH and FSH concentration; however, SS administration influenced gonadotropin secretion. We conclude that cortistatin play a regulatory role in pituitary secretion. Moreover, some differences have been found when compared cortistatin to somatostatin. Thus, when analyzing the mechanism of cortistatin activity it is worth to consider the effect of binding with receptors of somatostatin, specific receptor for CST (MrgX2) and GHS-R.
Topics: Animals; Follicle Stimulating Hormone; Growth Hormone; Luteinizing Hormone; Male; Neuropeptides; Prolactin; Radioimmunoassay; Rats; Rats, Inbred WKY; Somatostatin
PubMed: 19439817
DOI: No ID Found -
Peptides Nov 2009Melanin concentrating hormone (MCH) has been implicated in many brain functions and behaviors essential to the survival of animals. The hypothalamus is one of the... (Review)
Review
Melanin concentrating hormone (MCH) has been implicated in many brain functions and behaviors essential to the survival of animals. The hypothalamus is one of the primary targets where MCH-containing nerve fibers and MCH receptors are extensively expressed and its actions in the brain are exerted. Since the identification of MCH receptors as orphan G protein coupled receptors, the cellular effects of MCH have been revealed in many non-neuronal expression systems (including Xenopus oocytes and cell lines), however, the mechanism by which MCH modulates the activity in the neuronal circuitry of the brain is still under investigation. This review summarizes our current knowledge of electrophysiological effects of MCH on neurons in the hypothalamus, particularly in the lateral hypothalamus. Generally, MCH exerts inhibitory effects on neurons in this structure and may serve as a homeostatic regulator in the lateral hypothalamic area. Given the contrast between the limited data on cellular functions of MCH in the hypothalamus versus a fast growing body of evidence on the vital role of MCH in animal behavior, further investigations of the former are warranted.
Topics: Action Potentials; Animals; Cell Line; Cells, Cultured; Electrophysiology; Humans; Hypothalamic Hormones; Hypothalamus; Intracellular Signaling Peptides and Proteins; Melanins; Neurons; Neuropeptides; Orexins; Pituitary Hormones; Receptors, Pituitary Hormone
PubMed: 19463877
DOI: 10.1016/j.peptides.2009.05.006 -
Journal of Dairy Science Mar 1983I evaluated effects of ferulic acid on concentrations of endocrine hormones of eight Holstein heifers. Cattle were fitted with indwelling jugular cannulae 24 h before...
I evaluated effects of ferulic acid on concentrations of endocrine hormones of eight Holstein heifers. Cattle were fitted with indwelling jugular cannulae 24 h before experimentation. After control blood samples were taken, animals were assigned randomly to groups of four and infused with 100 or 500 mg of ferulic acid. Prolactin, growth hormone, luteinizing hormone, and thyroid hormones were measured in sera from blood samples. Blood sampling or ethanol infusion did not affect serum concentrations of prolactin. Serum prolactin was elevated 5 min after infusion of ferulic acid. Peak serum prolactin concentrations were 15 min after 100 mg of ferulic acid and between 10 and 30 min after 500 mg ferulic acid. Prolactin remained high until 120 min post drug administration. Control bleeding and ethanol administration did not alter serum growth hormone concentrations. Serum growth hormone concentrations were elevated slightly by ferulic acid. The increase was 5 min after drug administration. Baseline concentrations were established 60 to 90 min after administration. Ferulic acid did not affect luteinizing hormone or thyroid hormones. Ferulic acid, a constituent of corn and wheat germ, may affect release of pituitary hormones in cattle.
Topics: Animals; Cattle; Cattle Diseases; Cholagogues and Choleretics; Cinnamates; Coumaric Acids; Ethanol; Female; Growth Hormone; Hemorrhage; Luteinizing Hormone; Pituitary Hormones, Anterior; Prolactin; Thyroid Hormones; Thyroxine; Triiodothyronine
PubMed: 6841759
DOI: 10.3168/jds.S0022-0302(83)81834-7 -
Fertility and Sterility Nov 1971
Topics: Animals; Contraceptives, Oral; Estrogens; Female; Follicle Stimulating Hormone; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Luteinizing Hormone; Male; Ovary; Ovulation; Peptides; Pituitary Hormone-Releasing Hormones; Rats; Swine; Testis; Time Factors
PubMed: 4941683
DOI: No ID Found -
PloS One 2022Obesity is characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism, reducing fertility and increasing risk of pregnancy... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Obesity is characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism, reducing fertility and increasing risk of pregnancy complications and birth defects. We termed this phenotype 'Reprometabolic Syndrome' and showed that it can be recapitulated by acute infusions of lipid/insulin into healthy, normal weight, eumenorrheic women. Herein, we examined the broader impact of hyperlipidemia and euglycemic hyperinsulinemia on anterior pituitary trophic hormones and their targets.
METHODS
Serum FSH, LH, TSH, growth hormone (GH), prolactin (PRL), thyroid hormones (free T4, total T3), cortisol, IGF-1, adiponectin, leptin and creatinine were measured in a secondary analysis of an interventional crossover study of 12 normal weight cycling women who underwent saline and heparin (control) infusion, or a euglycemic insulin infusion with heparin and Intralipid® (lipid/insulin), between days 2-5 in sequential menstrual cycles.
RESULTS
In contrast to the decrease in gonadotropins, FSH and LH, infusion of lipid/insulin had no significant effects on other trophic hormones; TSH, PRL or GH. Thyroid hormones (fT4 and total T3), cortisol, IGF-1, adiponectin and creatinine also did not differ between saline or lipid/insulin infusion conditions. Leptin increased in response to lipid/insulin (p<0.02).
CONCLUSION
Acute hyperlipidemia and hyperinsulinemia exerted differential, cell type specific effects on the hypothalamic-pituitary-gonadal, adrenal and thyroid axes. Elucidation of mechanisms underlying the selective modulation of pituitary trophic hormones, in response to changes in diet and metabolism, may facilitate therapeutic intervention in obesity-related neuroendocrine and reproductive dysfunction.
Topics: Adiponectin; Creatinine; Cross-Over Studies; Female; Follicle Stimulating Hormone; Growth Hormone; Heparin; Human Growth Hormone; Humans; Hydrocortisone; Hyperinsulinism; Hyperlipidemias; Insulin; Insulin-Like Growth Factor I; Leptin; Lipids; Luteinizing Hormone; Obesity; Pituitary Hormones; Pregnancy; Prolactin; Thyroid Hormones; Thyrotropin
PubMed: 35544473
DOI: 10.1371/journal.pone.0268323 -
RNA Biology Dec 2020Growth hormone (GH), whose synthesis and release are mainly regulated by intracellular signals mediated by growth hormone-releasing hormone receptor (GHRHR), is one of...
Growth hormone (GH), whose synthesis and release are mainly regulated by intracellular signals mediated by growth hormone-releasing hormone receptor (GHRHR), is one of the major pituitary hormones and critical regulators of organism growth, metabolism, and immunoregulation. Pig GHRHR splice variants (SVs) may activate different signalling pathways via the variable C-terminal by alternative splicing, and SVs have the potential to change microRNA (miRNA) binding sites. In this study, we first confirmed the existence of pig GHRHR SVs (i.e., GHRHR, GHRHR SV1 and SV2) and demonstrated the inhibitory effects of critical pituitary miRNAs (i.e., let-7e and miR-328-5p) on GH synthesis and cell proliferation of primary pituitary cells. The SVs of targeted by let-7e and miR-328-5p were predicted via bioinformatics analysis and verified by performing dual-luciferase reporter assays and detecting the expression of target transcripts. The differential responses of let-7e, and miR-328-5p to GH-releasing hormone and the changes in signalling pathways mediated by GHRHR suggested that let-7e and miR-328-5p were involved in GH synthesis mediated by GHRHR SVs, indicating that the two miRNAs played different roles by different ways. Finally, results showed that the protein coded by the transcript regulated GH through the NO/NOS signalling pathway, whereas that coded by SV1 and SV2 regulated GH through the PKA/CREB signalling pathway, which was confirmed by the changes in signalling pathways after transfecting the expression vectors of SVs to GH3 cells. To the best of our knowledge, this paper is the first to report pituitary miRNAs regulate GH synthesis by targeting the different SVs of .
Topics: Alternative Splicing; Animals; Cell Line; Cell Proliferation; Cell Survival; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation; Growth Hormone; MicroRNAs; Nitric Oxide; Pituitary Gland; RNA Interference; Receptors, Pituitary Hormone-Regulating Hormone; Signal Transduction; Swine
PubMed: 32508238
DOI: 10.1080/15476286.2020.1778295 -
International Journal of Surgery... Apr 2016Traumatic brain injury (TBI) is a major cause of death and disability and may cause transient or persistent, isolated or multiple hypopituitarism in a variable...
BACKGROUND
Traumatic brain injury (TBI) is a major cause of death and disability and may cause transient or persistent, isolated or multiple hypopituitarism in a variable percentage of cases.
OBJECTIVES
The primary aim of this study was to determine the incidence of isolated and multiple anterior pituitary hormone deficiency in subjects with TBI in a single institution. The secondary aim was to determine a correlation between pituitary deficiency and quality of life (QOL) after TBI.
METHODS
Thirty-five patients, aged between 18 and 63 years, were evaluated 6months to 5 years after TBI. We evaluated the QOL by SF-12(®) questionnaire and measured serum basal GH, IGF1, LH, FSH, testosterone (in males), 17-β-estradiol (in women), PRL, fT4 and TSH. In patients with low IGF1, a GHRH + Arginine test was performed.
RESULTS
Single or multiple pituitary failure was found in 13 patients (37%). Low testosterone was found in 7 males, low FSH and/or LH in 4, low IGF1 in 7 patients. Hypogonadotropic hypogonadism and GH insufficiency assessed by GHRH + Arginine test were found respectively in 3 and 2 patients. One patient displayed a concomitant GH insufficiency and low TSH level. Twenty six patients showed a reduction in QOL. A correlations between altered QOL and hormonal deficiency was not observed.
CONCLUSIONS
Isolated or multiple hypopituitarism resulting from TBI are frequent. Alterations in QOL and pituitary function resulting from TBI are not associated.
Topics: Adolescent; Adult; Brain Injuries, Traumatic; Female; Gonadal Steroid Hormones; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Pituitary Hormones; Quality of Life; Young Adult
PubMed: 26708846
DOI: 10.1016/j.ijsu.2015.05.056