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Sample records for growth hormone binding

  1. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    PubMed Central

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-01-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions. PMID:3466175

  2. Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism)

    SciTech Connect

    Daughaday, W.H.; Trivedi, B.

    1987-07-01

    It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, the authors have examined the serum of three patients with Laron-type dwarfism, a condition in which GH refractoriness has been attributed to a defect in the GH receptor. The binding of /sup 125/I-labeled hGH incubated with serum has been measured after gel filtration of the serum through an Ultrogel AcA 44 minicolumn. Results are expressed as percent of specifically bound /sup 125/I-hGH and as specific binding relative to that of a reference serum after correction is made for endogenous GH. The mean +/- SEM of specific binding of sera from eight normal adults (26-46 years of age) was 21.6 +/- 0.45%, and the relative specific binding was 101.1 +/- 8.6%. Sera from 11 normal children had lower specific binding of 12.5 +/- 1.95% and relative specific binding of 56.6 +/- 9.1%. Sera from three children with Laron-type dwarfism lacked any demonstrable GH binding, whereas sera from 10 other children with other types of nonpituitary short stature had normal relative specific binding. They suggest that the serum GH-binding protein is a soluble derivative of the GH receptor. Measurement of the serum GH-binding protein may permit recognition of other abnormalities of the GH receptor.

  3. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone.

    PubMed Central

    Koenig, R J; Brent, G A; Warne, R L; Larsen, P R; Moore, D D

    1987-01-01

    Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. We have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. We show here that T3 receptor binds specifically to a site just upstream of the basal rGH promoter. This binding site includes two copies of a 7-base-pair direct repeat, the centers of which are separated by 10 base pairs. Deletions that specifically remove the T3 receptor binding site drastically reduce response to T3 in transient transfection experiments. These results demonstrate that T3 receptor can recognize specific DNA sequences and suggest that it can act directly as a positive transcriptional regulatory factor. Images PMID:3475698

  4. Growth hormone receptor/binding protein: Physiology and function

    SciTech Connect

    Herington, A.C.; Ymer, S.I.; Stevenson, J.L.; Roupas, P.

    1994-12-31

    Soluble truncated forms of the growth hormone receptor (GHR) are present in the circulation of many species and are also produced by many tissues/cell types. The major high-affinity forms of these GH-binding proteins (GHBP) are derived by alternative splicing of GHR mRNA in rodents, but probably by proteolytic cleavage in other species. Questions still remain with respect to the origins, native molecular forms(s), physiology, and function of the GHBPs, however. The observation that GH induces dimerization of the soluble GHBP and a membrane GHR, and that dimerization of GHR appears to be critical for GH bioactivity suggests that the presentation of GH to target cells, in an unbound form or as a monomeric or dimeric complex with GHBP, may have significant implications for the ability of GH to activate specific postreceptor signaling pathways (tyrosine kinase, protein kinase C, G-protein pathways) known to be utilized by GH for its diverse biological effects. This minireview addresses some of these aspects and highlights several new questions which have arisen as a result of recent advances in our understanding of the structure, function, and signaling mechanisms of the membrane bound GHR. 43 refs.

  5. Growth hormone.

    PubMed

    Bidlingmaier, Martin; Strasburger, Christian J

    2010-01-01

    Human growth hormone (hGH) is a proteohormone secreted by the pituitary gland. It acts through binding to the hGH receptor, inducing either direct effects or initiating the production of insulin-like growth-factor I (IGF-I), the most important mediator of hGH effects. Growth hormone is primarily known to promote longitudinal growth in children and adolescents, but has also various important metabolic functions throughout adult life. Effects of hGH on the adult organism are well established from studies with recombinant growth hormone (rhGH) therapy in growth hormone deficient subjects. In this particular group of patients, replacement of hGH leads to increased lipolysis and lean body mass, decreased fat mass, improvements in VO(2max), and maximal power output. Although extrapolation from these findings to the situation in well trained healthy subjects is impossible, and controlled studies in healthy subjects are scarce, abuse of hGH seems to be popular among athletes trying to enhance physical performance. Detection of the application of rhGH is difficult, especially because the amino acid sequence of rhGH is identical to the major 22,000 Da isoform of hGH normally secreted by the pituitary. Furthermore, some physiological properties of hGH secretion also hindered the development of a doping test: secreted in a pulsatile manner, it has a very short half-life in circulation, which leads to highly variable serum levels. Concentration alone therefore cannot prove the exogenous administration of hGH.Two approaches have independently been developed for the detection of hGH doping: The so-called "marker approach" investigates changes in hGH-dependent parameters like IGF-I or components of bone and collagen metabolism, which are increased after hGH injection. In contrast, the so-called "isoform approach" directly analyses the spectrum of molecular isoforms in circulation: the pituitary gland secretes a spectrum of homo- and heterodimers and - multimers of a variable

  6. Identification of prolactin and growth hormone binding proteins in rabbit milk.

    PubMed Central

    Postel-Vinay, M C; Belair, L; Kayser, C; Kelly, P A; Djiane, J

    1991-01-01

    Two distinct soluble proteins that specifically bind 125I-labeled human growth hormone (GH) are identified in the supernatant of ultracentrifuged rabbit milk, using HPLC gel filtration. The higher molecular weight proteins is GH specific, whereas the other one is specific for prolactin (PRL). The PRL-binding protein has a very high affinity for the hormone, almost 10 times higher than the affinity of the mammary gland membrane receptor. The PRL-binding protein is immunoprecipitated by a monoclonal antibody against the PRL receptor; another monoclonal antibody, which inhibits the PRL binding to mammary gland membranes, is a poor competitor for the PRL binding to the milk protein. These findings suggest that the milk PRL-binding protein corresponds to the binding domain of the receptor, but also that the conformation of the receptor and of the binding protein might differ. The milk and the plasma GH-binding proteins have a similar binding affinity. In cross-linking experiments using 125I-labeled human GH, the Mr of the GH-binding protein and of the PRL-binding protein were estimated to be 51,000 and 33,000, respectively. The binding proteins identified in the present work are probably responsible for the transport of their specific ligands in the milk. It is also conceivable that they have a role in the effects of GH and PRL in the mammary gland and/or the intestine of the young. Images PMID:1862093

  7. Analysis of growth hormone and lactogenic binding sites cross-linked to iodinated human growth hormone

    SciTech Connect

    Hughes, J.P.; Simpson, J.S.; Friesen, H.G.

    1983-06-01

    GH (GHR) and lactogenic receptors were analyzed after use of the cross-linking reagent ethylene glycol bis-(succinimidyl succinate) to attach covalently iodinated human GH (hGH) to binding proteins 1) on intact IM-9 lymphocytes, 2) in a partially purified GHR preparation from rabbit liver, and 3) in crude microsomal fractions from rabbit liver, rabbit mammary gland, and rat liver. The latter two microsomal preparations contain primarily lactogenic receptors, whereas in IM-9 lymphocytes and the rabbit liver preparations, GHR predominate. Cross-linked (125I)hGH-receptor complexes were solubilized, reduced, and separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of proteins cross-linked to (125I)hGH in the microsomal fraction from rabbit liver showed a specifically labeled complex with an estimated molecular weight (mol wt) of 75K. A slightly lower mol wt (71K) was determined for the complex labeled in the purified GHR preparation. In contrast to the relatively low mol wt complexes in rabbit liver, a complex that migrated with an apparent mol wt of 130K was identified in IM-9 lymphocytes. Labeled complexes were identified at 66K from rat liver and 61K from rabbit mammary gland. If it is assumed that hGH contributes 21K to the mol wt of the radiolabeled complexes, then the approximate mol wts of hGH-binding sites are 50-54K from rabbit liver, 109K from IM-9 lymphocytes, 45K from rat liver, and 40K from rabbit mammary gland.

  8. Growth Hormone

    MedlinePlus

    ... the dose of glucose. Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1) . ... regular intervals for years afterward to monitor GH production and to detect tumor recurrence. Other blood tests ...

  9. The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor.

    PubMed Central

    Moore, D D; Marks, A R; Buckley, D I; Kapler, G; Payvar, F; Goodman, H M

    1985-01-01

    Glucocorticoid receptor (GCR) protein stimulates transcription from a variety of cellular genes. We show here that GCR partially purified from rat liver binds specifically to a site within the first intron of the human growth hormone (hGH) gene, approximately 100 base pairs downstream from the start of hGH transcription. GCR binding is selectively inhibited by methylation of two short, symmetrically arranged clusters of guanine residues within this site. A cloned synthetic 24-base-pair deoxyoligonucleotide containing the predicted GCR binding sequence interacts specifically with GCR. The hGH binding site shares sequence homology with a GCR binding site upstream from the human metallothionein II gene and a subset of GCR binding sites from mouse mammary tumor virus. All of these binding sites for this eukaryotic transcriptional regulatory protein show remarkable similarity in overall geometry to the binding sites for several prokaryotic transcriptional regulatory proteins. Images PMID:2983311

  10. Binding and degradation of (/sup 125/I)human growth hormone in rat adipocytes

    SciTech Connect

    Gorin, E.; Grichting, G.; Goodman, H.M.

    1984-08-01

    Iodinated human growth hormone (( /sup 125/I)hGH) binds to both specific and nonspecific sites on the surface of adipocytes isolated from the epididymal fat of normal rats. When adipocytes were incubated at 37 C with 1 nM (/sup 125/I)hGH, specific binding increased for 30-60 min and thereafter remained approximately constant as long as the hormone was present in the medium. About 90% of the /sup 125/I released was soluble in 5% trichloroacetic acid and was in the form of iodotyrosine. The rate of /sup 125/I release from specific binding sites decreased by a factor of 4 when the temperature was lowered from 37 to 17 C. Replacement of some of the sodium chloride in the buffer with 25 mM ammonium chloride had little or no effect on the amount on /sup 125/I that bound to cells when (/sup 125/I)hGH was present in the medium, but completely blocked the release of /sup 125/I from cells transferred to hormone-free medium. Ammonium chloride also significantly reduced both the release of /sup 125/I from nonspecific binding sites and the amount of /sup 125/I recovered in trichloroacetic acid-soluble form. Cloroquine, leupeptin, or colchicine nearly doubled the specific binding of (/sup 125/I)hGH after 180 min and markedly slowed the release of /sup 125/I when cells were transferred to hormone-free medium. All of these agents also significantly reduced the rate of release of /sup 125/I from nonspecific binding sites. Incubation of adipose tissue from hypophysectomized rats with ammonium chloride, leupeptin, or colchicine failed to alter the ability of GH to increase glucose oxidation, induce refractoriness, or promote lipolysis in the presence of theophylline.

  11. Binding proteins for growth hormone and prolactin in rabbit kidney cytosol

    SciTech Connect

    Herington, A.C.; Stevenson, J.L.; Ymer, S.I. )

    1988-09-01

    Two soluble, receptor-like binding proteins with apparent somatotrophic (growth hormone (GH)) and lactogenic (prolactin (PRL)) specificities, respectively, and that are present in rabbit kidney cytosol have now been examined in more detail using specific GH receptor and PRL receptor monoclonal antibodies (MAb). Gel chromatography of {sup 125}I-labeled human GH ({sup 125}I-hGH) kidney cytosol complexes in the absence of these MAbs revealed two specifically bound regions of radioactivity at molecular weights (MW) of {approximately}120,000 and {approximately}60,000, which are similar in size to complexes formed by the native GH receptor of rabbit liver cytosol and the PRL receptor of mammary gland. Co-incubation with GH-receptor MAb inhibited {sup 125}I-hGH binding only to the higher MW (120,000) species, whereas the PRL-receptor MAb inhibited only the lower MW (60,000) species, thus establishing definitively the hormonal specificities of the two binding proteins. The presence of both GH- and PRL-specific binding subunits in cytosol was confirmed using covalent cross-linking techniques. No GH binding protein was detected in kidney membranes. The presence of naturally soluble, receptor-like binding proteins for GH and PRL in kidney cytosol preparations raises the possibility of their playing a role in the intracellular regulation of kidney function and/or metabolism.

  12. The structure and regulation of expression of the mouse growth hormone receptor and binding protein

    SciTech Connect

    Talamantes, F.

    1994-12-31

    The mouse growth hormone receptor (mGHR) and the mouse growth hormone-binding protein (mGHBP) are products of a single gene which are generated alternative splicing. The factors that regulate the expression of mGHR and mGHBP mRNA and protein during pregnancy in the mouse are incompletely understood. During pregnancy in the mouse, there are parallel increases in circulating mouse growth hormone (mGH), liver mGHR, and serum mGHBP. The increase in both hepatic mGHR and serum mGHBP begins on Day 9 of gestation and by late gestation the hepatic mGHR content has increased 8-fold and serum mGHBP has increased 30-fold compared with values in nonpregnant controls. A parallel increase occurs in the steady state levels of liver GHR and GHBP encoding mRNAs. The increase in both messages begins on Day 9 of gestation; however, the GHR mRNA reaches maximum levels by Day 13, while the GHBP mRNA continues to increase until the end of pregnancy. The magnitude of the increase in the GHR-encoding message is 15- to 20-fold between nonpregnant and late pregnant mice, and the magnitude of the increase in the GHBP-encoding message is 30- to 50-fold. Both pituitary mGH and the number of conceptuses influence the receptors and binding protein for mGH during pregnancy. 22 refs.

  13. Identification and characterization of specific binding proteins for growth hormone in normal human sera.

    PubMed Central

    Herington, A C; Ymer, S; Stevenson, J

    1986-01-01

    The well-recognized "big" forms (45,000-100,000 mol wt) of immunoreactive human growth hormone (hGH) in human serum have been reported to be random aggregates or formal polymers. However, we have now investigated the possibility that they are protein-bound forms. After incubation of monomeric 125I-hGH with normal serum, gel chromatography indicated a peak of bound 125I-hGH (at approximately 120,000 mol wt), which was completely displaced by excess unlabeled hGH. When serum alone was chromatographed two peaks of specific binding were subsequently detected, the major peak, eluting between 74,000 and 85,000 mol wt corresponded to the 125I-hGH-binding protein complex observed at approximately 120,000 mol wt. Using a mini-gel filtration system for separating bound from free hormone, binding of 125I-hGH by normal human serum was dependent on time (equilibrium was reached in 2 h at 21 degrees C), temperature (21 degrees C greater than 37 degrees C), Ca2+ and serum concentrations. Binding was reversible and highly specific for hGH, not being displayed by GH or prolactins from several species. Scatchard analysis revealed linear plots with an affinity (KA) of 0.32 +/- 0.06 X 10(9) M-1 (n = 7). Human serum with low endogenous hGH levels, when added to rabbit liver membranes, decreased the binding of 125I-hGH in this tissue in a dose-dependent manner. These data indicate that human sera contain a specific, high affinity binding protein for hGH and that this may account, at least in part, for the known size heterogeneity of GH in serum. Its effect on GH binding to target tissues may indicate a role for the binding protein in the regulation of GH action. PMID:3711337

  14. Somatotroph- and lactotroph-specific interactions with the homeobox protein binding sites in the rat growth hormone gene promoter.

    PubMed Central

    Schaufele, F; West, B L; Reudelhuber, T

    1990-01-01

    Nuclear extracts prepared from growth hormone-secreting (GC) and prolactin-secreting (235-1) rat anterior pituitary cell lines were compared for their ability to bind to the DNA sequences conferring tissue-specificity to the expression of the rat growth hormone (rGH) gene promoter. Cell-specific differences in the interaction of Pit-1, a tissue-specific member of the POU-domain transcription factor family, with the pGHF1 binding site were detected by methylation interference experiments; otherwise the Pit-1 proteins present in GC cell and 235-1 cell extracts were similar. Two other protein/DNA complexes, GHF5 and GHF7, were detected by gel mobility shift assays and the binding of both complexes to the rGH promoter depended upon DNA sequences contained within the two binding sites for Pit-1. In contrast to Pit-1 which can bind to either of the two sites independently, a single Pit-1 binding site was insufficient for GHF5 and GHF7 binding; i.e. both Pit-1 binding sites within the rGH promoter were required. Whereas GHF5 was present in nuclear extracts of GC cells and a variety of cells not producing growth hormone, GHF7 binding activity was detected only in the GC cell line (and not in the 235-1 cell line). GHF7 binding activity was therefore more closely correlated with growth hormone gene transcription than was Pit-1. rGH promoters containing mutations which inhibited GHF5, GHF7 and Pit-1 binding were expressed less efficiently than the wild type promoter after transfection into GC cells. One promoter mutation to which the GHF7 complex but not the Pit-1 factor can bind was also transcription deficient demonstrating that Pit-1 binding, independent of GHF7 binding, was nevertheless important to the expression of the rat growth hormone promoter. Images PMID:1976240

  15. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth.

    PubMed

    Holst, Frederik; Hoivik, Erling A; Gibson, William J; Taylor-Weiner, Amaro; Schumacher, Steven E; Asmann, Yan W; Grossmann, Patrick; Trovik, Jone; Necela, Brian M; Thompson, E Aubrey; Meyerson, Matthew; Beroukhim, Rameen; Salvesen, Helga B; Cherniack, Andrew D

    2016-01-01

    The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. PMID:27160768

  16. Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth

    PubMed Central

    Holst, Frederik; Hoivik, Erling A.; Gibson, William J.; Taylor-Weiner, Amaro; Schumacher, Steven E.; Asmann, Yan W.; Grossmann, Patrick; Trovik, Jone; Necela, Brian M.; Thompson, E. Aubrey; Meyerson, Matthew; Beroukhim, Rameen; Salvesen, Helga B.; Cherniack, Andrew D.

    2016-01-01

    The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications. PMID:27160768

  17. Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism.

    PubMed Central

    Edery, M; Rozakis-Adcock, M; Goujon, L; Finidori, J; Lévi-Meyrueis, C; Paly, J; Djiane, J; Postel-Vinay, M C; Kelly, P A

    1993-01-01

    A single point mutation in the growth hormone (GH) receptor gene generating a Phe-->Ser substitution in the extracellular binding domain of the receptor has been identified in one family with Laron type dwarfism. The mutation was introduced by site-directed mutagenesis into cDNAs encoding the full-length rabbit GH receptor and the extracellular domain or binding protein (BP) of the human and rabbit GH receptor, and also in cDNAs encoding the full length and the extracellular domain of the related rabbit prolactin (PRL) receptor. All constructs were transiently expressed in COS-7 cells. Both wild type and mutant full-length rabbit GH and PRL receptors, as well as GH and prolactin BPs (wild type and mutant), were detected by Western blot in cell membranes and concentrated culture media, respectively. Immunofluorescence studies showed that wild type and mutant full-length GH receptors had the same cell surface and intracellular distribution and were expressed with comparable intensities. In contrast, all mutant forms (full-length receptors or BPs), completely lost their modify the synthesis ligand. These results clearly demonstrate that this point mutation (patients with Laron syndrome) does not modify the synthesis or the intracellular pathway of receptor proteins, but rather abolishes ability of the receptor or BP to bind GH and is thus responsible for the extreme GH resistance in these patients. Images PMID:8450064

  18. Growth hormone test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003706.htm Growth hormone test To use the sharing features on this page, please enable JavaScript. The growth hormone test measures the amount of growth hormone in ...

  19. Growth hormone (GH) binding and effects of GH analogs in transgenic mice

    SciTech Connect

    Bartke, A.; Steger, R.W.; Turyn, D.

    1994-12-31

    Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb{sub 2} cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo. 35 refs.

  20. Regulation of the growth hormone (GH) receptor and GH-binding protein mRNA

    SciTech Connect

    Kaji, Hidesuke; Ohashi, Shin-Ichirou; Abe, Hiromi; Chihara, Kazuo

    1994-12-31

    In fasting rats, a transient increase in growth hormone-binding protein (GHBP) mRNA levels was observed after 1 day, in muscle, heart, and liver, but not in fat tissues. The liver GH receptor (GHR) mRNA level was significantly increased after 1 day (but not after 5 days) of bovine GH (bGH) treatment in fed rats. Both the liver GHR mRNA level and the net increment of plasma IGF-I markedly decreased after 5 days of bGH administration in fasting rats. These findings suggest that GHR and GHBP mRNAs in the liver are expressed in a different way and that the expression of GHBP mRNA is regulated differently between tissues, at least in rats. The results also suggest that refractoriness to GH in a sustained fasting state might be beneficial in preventing anabolic effects of GH. In humans, GHR mRNA in lymphocytes, from subjects with either GH-deficiency or acromegaly, could be detected by the reverse transcription-polymerase chain reaction method. In one patient with partial GH insensitivity, a heterozygous missense mutation (P561T) was identified in the cytoplasmic domain of GHR. 15 refs., 4 figs.

  1. Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone-binding protein

    SciTech Connect

    Shemshedini, L.; Wilson, T.G. )

    1990-03-01

    The Met mutant of Drosophila melanogaster is highly resistant to juvenile hormone III (JH III) or its chemical analog, methoprene, an insect growth regulator. Five major mechanisms of insecticide resistance were examined in Met and susceptible Met{sup +} flies. These two strains showed only minor differences when penetration, excretion, tissue sequestration, or metabolism of ({sup 3}H)JH III was measured. In contrast, when we examined JH III binding by a cytosolic binding protein from a JH target tissue, Met strains had a 10-fold lower binding affinity than did Met{sup +} strains. Studies using deficiency-bearing chromosomes provide strong evidence that the Met locus controls the binding protein characteristics and may encode the protein. These studies indicate that resistance in Met flies results from reduced binding affinity of a cytosolic binding protein for JH III.

  2. Growth hormone deficiency - children

    MedlinePlus

    ... the same age. The child will have normal intelligence in most cases. In older children, puberty may ... hormones cause the body to make. Tests can measure these growth factors. Accurate growth hormone deficiency testing ...

  3. Nutritional status and growth hormone regulate insulin-like growth factor binding protein (igfbp) transcripts in Mozambique tilapia

    PubMed Central

    Breves, Jason P.; Tipsmark, Christian K.; Stough, Beth A.; Seale, Andre P.; Flack, Brenda R.; Moorman, Benjamin P.; Lerner, Darren T.; Grau, E. Gordon

    2014-01-01

    Growth in teleosts is controlled in large part by the activities of the growth hormone (Gh)/insulin-like growth factor (Igf) system. In this study, we initially identified igf-binding protein (bp)1b, -2b, -4, -5a and -6b transcripts in a tilapia EST library. In Mozambique tilapia (Oreochromis mossambicus), tissue expression profiling of igfbps revealed that igfbp1b and -2b had the highest levels of expression in liver while igfbp4, -5a and -6b were expressed at comparable levels in most other tissues. We compared changes in hepatic igfbp1b, -2b and -5a expression during catabolic conditions (28 days of fasting) along with key components of the Gh/Igf system, including plasma Gh and Igf1 and hepatic gh receptor (ghr2), igf1 and igf2 expression. In parallel with elevated plasma Gh and decreased Igf1 levels, we found that hepatic igfbp1b increased substantially in fasted animals. We then tested whether systemic Gh could direct the expression of igfbps in liver. A single intraperitoneal injection of ovine Gh into hypophysectomized tilapia specifically stimulated liver igfbp2b expression along with plasma Igf1 and hepatic ghr2 levels. Our collective data suggest that hepatic endocrine signaling during fasting may involve post-translational regulation of plasma Igf1 via a shift towards the expression of igfbp1b. Thus, Igfbp1b may operate as a molecular switch to restrict Igf1 signaling in tilapia; furthermore, we provide new details regarding isoform-specific regulation of igfbp expression by Gh. PMID:24818968

  4. [Growth hormone treatment update].

    PubMed

    2014-02-01

    Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

  5. Dermatophyte-hormone relationships: characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum.

    PubMed Central

    Clemons, K V; Schär, G; Stover, E P; Feldman, D; Stevens, D A

    1988-01-01

    We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the fungus. We report here studies which characterize more fully the specific binding properties and the functional responses of T. mentagrophytes and taxonomically related fungi to a series of mammalian steroid hormones. Scatchard analysis of [3H]progesterone binding in both the + and - mating types of Arthroderma benhamiae and in Microsporum canis revealed a single class of binding sites with approximately the same affinity as that in T. mentagrophytes (Kd, 1 X 10(-7) to 2 X 10(-7) M). Trichophyton rubrum had a protein with a higher binding affinity (Kd, 1.6 X 10(-8) M). Characterization of the [3H]progesterone-binding sites in T. mentagrophytes showed the binder to be a protein which was destroyed by trypsin and heating to 56 degrees C. Previous examination of the steroid-binding specificity in T. mentagrophytes had demonstrated that deoxycorticosterone (DOC) and dihydrotestosterone (DHT) were effective competitors for [3H]progesterone binding. Expansion of this study to include other competitors revealed that R5020 (a synthetic progestin), androstenedione, and dehydroepiandosterone possessed relative binding affinities which were 20, 11, and 9% of that of progesterone, respectively. Other ligands tested were less effective. Competition studies for the binder in M. canis resulted in similar findings: DOC and DHT were effective competitors for [3H]progesterone binding. The growth of A. benhamiae + and -, M. canis, and T. rubrum were all inhibited by progesterone in a dose-responsive manner, with 50% inhibition achieved at concentrations of 9.8 x 10(-6), 1.2 x 10(-5), 1.5 x 10(-5), and 2.7 x 10(-6) M. respectively,. PMID:3182998

  6. Human growth hormone.

    PubMed

    Strobl, J S; Thomas, M J

    1994-03-01

    The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID:8190748

  7. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein

    SciTech Connect

    Lim, Jung Yeon; Kim, Hongtae; Jeun, Sin-Soo . E-mail: ssjeun@catholic.ac.kr; Kang, Seok-Gu; Lee, Kyung-Jin

    2006-02-24

    Numerous studies have suggested that the NF2 protein merlin is involved in the regulation of abnormal cell growth and proliferation. In this study, to better understand the merlin's mechanisms that contribute to the inhibition of tumorigenesis, we examined the potential action of merlin on the cell proliferative signaling pathways in response to growth hormone (GH). Merlin effectively attenuated the GH-induced serum response element (SRE) and Elk-1-mediated transcriptional activation, as well as the endogenous SRE-regulated gene c-fos expression in NIH3T3 cells. In addition, merlin prevented the Raf-1 complex activation process, which resulted in the suppression of MAP kinase/ERK, extracellular signal-regulated kinase (ERKs), and Elk-1 phosphorylation, which are the downstream signals of Raf-1. Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression. These results suggest that merlin contributes, via its protein-to-protein interaction with Grb2 and consequent inhibition of the MAPK pathways, to the regulation of the abnormal cell proliferation, and this provides a further mechanism underlying the tumor suppressor function of merlin.

  8. Thyroid-stimulating hormone receptor levels and binding affinity in the thyroid gland of growth-retarded mice.

    PubMed

    Kobayashi, Kenichi; Sato, Mirei; Machida, Takeo; Kobayashi, Tetsuya

    2005-09-01

    Growth-retarded (grt/grt) mice are congenitally primary hypothyroid. Our previous study indicated that thyroid-stimulating hormone (TSH) responsiveness was defective in the grt/grt thyroid gland. We now report additional studies of impaired grt/grt thyroid function. Semiquantitative RT-PCR confirmed that TSH receptor (TSHR) mRNA expression in the grt/grt thyroid was significantly decreased compared with +/+ thyroids. Scatchard analysis revealed that grt/grt and +/+ mice have only one type of TSH binding site. grt/grt thyroids had fewer TSH binding sites, although this did not apparently affect the affinity of TSH for its receptor. The present data suggest that reduced TSHR levels or defects in TSHR signaling could be one of the possible defective sites in the grt/grt thyroid gland.

  9. In silico investigation of pH-dependence of prolactin and human growth hormone binding to human prolactin receptor

    PubMed Central

    Wang, Lin; Witham, Shawn; Zhang, Zhe; Li, Lin; Hodsdon, Michael E.; Alexov, Emil

    2011-01-01

    Experimental data shows that the binding of human prolactin (hPRL) to human prolactin receptor (hPRLr-ECD) is strongly pH-dependent, while the binding of the same receptor to human growth hormone (hGH) is pH-independent. Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids. It is shown that the computational modeling correctly predicts experimentally determined pKa’s of histidine residues in an unbound state in the majority of the cases and the pH-dependence of the binding free energy. Structural analysis carried in conjunction with calculated pH-dependence of the binding revealed that the main reason for pH-dependence of the binding of hPRL-hPRLr-ECD is a number of salt- bridges across the interface of the complex, while no salt-bridges are formed in the hGH-hPRlr-ECD. Specifically, most of the salt-bridges involve histidine residues and this is the reason for the pH-dependence across a physiological range of pH. The analysis not only revealed the molecular mechanism of the pH-dependence of the hPRL-hPRLr-ECD, but also provided critical insight into the underlying physic-chemical mechanism. PMID:24683423

  10. Bovine serum thyroxine, prolactin, growth hormone, glucocorticoid, and thyroxine binding globulin response to thyroprotein.

    PubMed

    Shaw, G H; Convey, E M; Tucker, H A; Reineke, E P; Thomas, J W; Byrne, J J

    1975-05-01

    Twenty-one lactating Holstein cows were assigned randomly to groups of seven and received: (1) no treatment; (2) 15 g thyroprotein daily for 5 wk; or (3) 15 g thyroprotein daily for 13 wk. Combined averages for serum thyroxine of cows in thyroprotein groups increased linearly from a baseline of 54 ng/ml to a peak of 135 ng/ml at 6 days after thyroprotein feeding was begun. Serum thyroxine then decreased to approximately 80 ng/ml at 23 days of thyroprotein feeding which was maintained during the remainder of the feeding period. Following thyroprotein withdrawal from the diet serum thyroxine concentration decreased to 24 ng/ml at 6 days. Neither serum prolactin, growth hormone, nor total glucocorticoids were affected by thyroprotein feeding or withdrawal. Average milk production of cows in the control group decreased linearly with time. Milk production of cows fed thyroprotein for 5 wk averaged 2.2 to 3.3 kg/day more than cows in the control group and that of cows fed thyroprotein for 13 wk averaged .95 to 2.5 kg/day more than controls for 60 days, but between 60 and 91 days it was .9 kg/day less than controls.

  11. Growth Hormone Promotes Lymphangiogenesis

    PubMed Central

    Banziger-Tobler, Nadja Erika; Halin, Cornelia; Kajiya, Kentaro; Detmar, Michael

    2008-01-01

    The lymphatic system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined using comparative transcriptional profiling studies of cultured lymphatic endothelial cells versus blood vascular endothelial cells, growth hormone receptor was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Growth hormone induced in vitro proliferation, sprouting, tube formation, and migration of lymphatic endothelial cells, and the mitogenic effect was independent of vascular endothelial growth factor receptor-2 or -3 activation. Growth hormone also inhibited serum starvation-induced lymphatic endothelial cell apoptosis. No major alterations of lymphatic vessels were detected in the normal skin of bovine growth hormone-transgenic mice. However, transgenic delivery of growth hormone accelerated lymphatic vessel ingrowth into the granulation tissue of full-thickness skin wounds, and intradermal delivery of growth hormone resulted in enlargement and enhanced proliferation of cutaneous lymphatic vessels in wild-type mice. These results identify growth hormone as a novel lymphangiogenic factor. PMID:18583315

  12. Growth hormone and growth?

    PubMed

    Harvey, Steve

    2013-09-01

    Pituitary GH is obligatory for normal growth in mammals, but the importance of pituitary GH in avian growth is less certain. In birds, pituitary GH is biologically active and has growth promoting actions in the tibia-test bioassay. Its importance in normal growth is indicated by the growth suppression following the surgical removal of the pituitary gland or after the immunoneutralization of endogenous pituitary GH. The partial restoration of growth in some studies with GH-treated hypophysectomized birds also suggests GH dependency in avian growth, as does the dwarfism that occurs in some strains with GHR dysfunctions. Circulating GH concentrations are also correlated with body weight gain, being high in young, rapidly growing birds and low in slower growing older birds. Nevertheless, despite these observations, there is an extensive literature that concludes pituitary GH is not important in avian growth. This is based on numerous studies with hypophysectomized and intact birds that show only slight, transitory or absent growth responses to exogenous GH-treatment. Moreover, while circulating GH levels correlate with weight gain in young birds, this may merely reflect changes in the control of pituitary GH secretion during aging, as numerous studies involving experimental alterations in growth rate fail to show positive correlations between plasma GH concentrations and the alterations in growth rate. Furthermore, growth is known to occur in the absence of pituitary GH, as most embryonic development occurs prior to the ontogenetic appearance of pituitary somatotrophs and the appearance of GH in embryonic circulation. Early embryonic growth is also independent of the endocrine actions of pituitary GH, since removal of the presumptive pituitary gland does not impair early growth. Embryonic growth does, however, occur in the presence of extrapituitary GH, which is produced by most tissues and has autocrine or paracrine roles that locally promote growth and development

  13. Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging.

    PubMed

    Arum, Oge; Saleh, Jamal; Boparai, Ravneet; Turner, Jeremy; Kopchick, John; Khardori, Romesh; Bartke, Andrzej

    2014-01-01

    The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice. PMID:25789159

  14. [Hormones and hair growth].

    PubMed

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  15. Effects of oral contraceptives on diurnal profiles of insulin, insulin-like growth factor binding protein-1, growth hormone and cortisol in endurance athletes with menstrual disturbance

    PubMed Central

    Rickenlund, A.; Thorén, M.; Nybacka, Å.; Frystyk, J.; Hirschberg, A. Lindén

    2010-01-01

    BACKGROUND Menstrual disturbances in female athletes are often explained as a consequence of energy deficiency. Oral contraceptive (OC) treatment may have favorable metabolic effects. We evaluated effects of OCs on diurnal secretions of insulin, insulin-like growth factor binding protein 1 (IGFBP-1), growth hormone (GH) and cortisol in relation to changes in body composition in athletes with menstrual disturbance compared with regularly menstruating athletes and controls. METHODS Age- and BMI-matched groups of endurance athletes with menstrual disturbance (OAM, n = 9) and regularly cycling athletes (RM, n = 8) and sedentary controls (CTRL, n = 8) were examined, and hormone levels measured, before and after 8 months of treatment with a low-dose combined OC (30 µg ethinyl estradiol + 150 µg levonorgestrel). RESULTS Before OC treatment, the diurnal profile of insulin was lower (P < 0.01) and levels of IGFBP-1 (P < 0.05) and cortisol (P < 0.05) were higher in OAM athletes than in CTRL, whereas GH secretion was higher than in RM athletes (P < 0.05). After treatment, diurnal secretions of these hormones were similar between groups with an increase of IGFBP-1 in the regularly menstruating subjects only (P < 0.001). OC treatment increased body fat mass in OAM athletes (P < 0.01 versus baseline). The change in total fat mass correlated positively with pretreatment diurnal levels of GH (rs = 0.67, P < 0.01) and cortisol (rs = 0.64, P < 0.01). CONCLUSIONS OC treatment in endurance athletes with menstrual disturbance increases body fat mass and results in diurnal levels of insulin, IGFBP-1, GH and cortisol that are comparable to those in regularly menstruating subjects. These results suggest that OCs improve metabolic balance in OAM athletes. PMID:19840988

  16. Relationship between serum growth hormone binding protein levels and height in young men.

    PubMed

    Codner, E; Mericq, M V; Maheshwari, H G; Iñguez, G; Capurro, M T; Salazar, T; Baumann, G; Cassorla, F; Codner, D E

    2000-01-01

    The biochemical mediators responsible for variations in stature among normal subjects are largely unknown. To obtain some initial information about potential endocrine factors, we measured the serum concentrations of GH, IGF-1, IGFBP-3 and GHBP in healthy young men shorter than 159 cm and taller than 187 cm. We studied 14 volleyball and basketball players (tall group), and 14 jockey students from a horse racetrack (short group). A careful medical history was taken, including dietary intake, and physical examination with special attention to the possible presence of genetic stigmata was performed. Serum prealbumin was determined as an index of nutritional status. A buccal smear was performed to exclude Klinefelter's syndrome. The BMI and serum prealbumin levels were comparable in both groups of individuals. The nutritional survey, however, revealed that the tall subjects had a higher intake of calories (42.2+/-11.2 vs. 30.1+/-15.15 kcal/kg, p<0.05), and protein (1.5+/-0.6 vs. 0.8+/-0.4 mg/kg, p<0.01). Serum concentrations of GHBP did not differ in the two groups (0.95+/-0.37 nmol/l in the tall, and 0.95+/-0.53 nmol/l in the short group), and did not correlate with height, serum IGF-I levels, or BMI. We observed a significant difference in the serum concentrations of IGF-I in the two groups of individuals (42.02+/-9.37 nmol/l in the tall and 31.79+/-3.18 nmol/l in the short group, p<0.05), and this growth factor showed a positive correlation with height (r = 0.5, p<0.01). These preliminary findings suggest that final height differences in young men do not appear to be mediated by variations in GHBP concentrations.

  17. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene.

    PubMed Central

    Slater, E P; Rabenau, O; Karin, M; Baxter, J D; Beato, M

    1985-01-01

    In this study DNA-binding and gene transfer experiments were performed to examine a potential glucocorticoid regulatory element (GRE) in the human growth hormone gene. As assayed by nitrocellulose filter binding, only two regions of the human growth hormone gene, the 5'-flanking sequences and a fragment containing part of the first intron, were retained preferentially by purified glucocorticoid-receptor complexes. The relative binding by the transcribed sequences was three times greater than the relative binding by the 5'-flanking sequences, but less than the relative binding by a fragment containing the human metallothionein-IIA gene GRE. The intron, but not the 5'-flanking sequences, generated a "footprint" when the receptor complex was used to protect the segments against exonuclease III digestion; the protected sequence spanned nucleotides +86 to +115 in the first intron and contained a structure homologous in 14 of 16 nucleotides to a 16-nucleotide consensus GRE. The hexanucleotide 5'-TGTCCT-3', thought to be important for GRE activity, not only was found in this sequence and in the 5'-flanking region, but also was present twice in the 3' end of the gene that did not show specific receptor binding. The latter results suggest that the hexanucleotide alone is not sufficient to generate specific receptor binding tight enough to be assayed in this way. To test the biological activity of the intron binding site, a fragment containing these sequences was fused 5' to the human metallothionein-IIA gene promoter depleted of its GRE and linked to the structural sequences of the herpes simplex virus thymidine kinase (TK) gene. When this hybrid gene was transfected into Rat 2 TK- cells, its expression was induced threefold by the glucocorticoid dexamethasone, as assessed by transfection efficiency and RNA blotting analyses. Expression of the same gene without the human growth hormone gene segment was not affected by the steroid, whereas the wild-type human metallothionein

  18. Biosimilar growth hormone.

    PubMed

    Saenger, Paul

    2012-01-01

    As the first wave of biopharmaceuticals is expiring, biosimilars or follow-on -protein products (FOPP's) have emerged. Biosimilar drugs are cheaper than the originator/comparator drug. The regulatory foundation for these products is more advanced and better codified in Europe than in the US. Biosimilar soamtropin has been approved in both the US and Europe. The scientific viability of biosimilar drugs and especially growth hormone has been proven by several rigorously conducted clinical trials. Efficacy and safety data (growth rates, IGF-1 generation) for up to 7 y for pediatric indications measure up favorably to previously approved growth hormones which served as reference comparators. The Obama Administration appears to be committed to establish innovative pathways for the approval of biologics and biosimilars in the US. The cost savings in health care expenditures will be substantial as the global sales of biologics have reached $ 93 billion in 2009.

  19. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  20. Extrapituitary growth hormone and growth?

    PubMed

    Harvey, Steve; Baudet, Marie-Laure

    2014-09-01

    While growth hormone (GH) is obligatory for postnatal growth, it is not required for a number of growth-without-GH syndromes, such as early embryonic or fetal growth. Instead, these syndromes are thought to be dependent upon local growth factors, rather than pituitary GH. The GH gene is, however, also expressed in many extrapituitary tissues, particularly during early development and extrapituitary GH may be one of the local growth factors responsible for embryonic or fetal growth. Moreover, as the expression of the GH receptor (GHR) gene mirrors that of GH in extrapituitary tissues the actions of GH in early development are likely to be mediated by local autocrine or paracrine mechanisms, especially as extrapituitary GH expression occurs prior to the ontogeny of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of pituitary somatotrophs or the appearance of GH in the circulation. The extrapituitary expression of GH in embryos has also been shown to be of functional relevance in a number of species, since the immunoneutralization of endogenous GH or the blockade of GH production is accompanied by growth impairment or cellular apoptosis. The extrapituitary expression of the GH gene also persists in some central and peripheral tissues postnatally, which may reflect its continued functional importance and physiological or pathophysiological significance. The expression and functional relevance of extrapituitary GH, particularly during embryonic growth, is the focus of this brief review.

  1. Extrapituitary growth hormone.

    PubMed

    Harvey, S

    2010-12-01

    Pituitary somatotrophs secrete growth hormone (GH) into the bloodstream, to act as a hormone at receptor sites in most, if not all, tissues. These endocrine actions of circulating GH are abolished after pituitary ablation or hypophysectomy, indicating its pituitary source. GH gene expression is, however, not confined to the pituitary gland, as it occurs in neural, immune, reproductive, alimentary, and respiratory tissues and in the integumentary, muscular, skeletal, and cardiovascular systems, in which GH may act locally rather than as an endocrine. These actions are likely to be involved in the proliferation and differentiation of cells and tissues prior to the ontogeny of the pituitary gland. They are also likely to complement the endocrine actions of GH and are likely to maintain them after pituitary senescence and the somatopause. Autocrine or paracrine actions of GH are, however, sometimes mediated through different signaling mechanisms to those mediating its endocrine actions and these may promote oncogenesis. Extrapituitary GH may thus be of physiological and pathophysiological significance.

  2. Growth hormone neurosecretory dysfunction.

    PubMed

    Bercu, B B; Diamond, F B

    1986-08-01

    The basis for understanding clinical disorders in the neuroregulation of GH secretion is derived from the complexity of the CNS-hypothalamic-pituitary axis. Studies in animals and humans demonstrate an anatomic, physiological and pharmacological evidence for neurosecretory control over GH secretion including neurohormones (GRH, somatostatin), neurotransmitters (dopaminergic, adrenergic, cholinergic, serotonergic, histaminergic, GABAergic), and neuropeptides (gut hormones, opioids, CRH, TRH, etc). The observation of a defect in the neuroregulatory control of GH secretion in CNS-irradiated humans and animals led to the hypothesis of a disorder in neurosecretion, GHND, as a cause for short stature. We speculate that in this heterogeneous group of children a disruption in the neurotransmitter-neurohormonal functional pathway could modify secretion ultimately expressed as poor growth velocity and short stature.

  3. Effects of Divalent Cations and Disulfide Bond Reducing Agents on Specific Binding of Growth Hormone to Liver Membrane Receptors from Snakehead Fish (Ophiocephalus argus, Cantor).

    PubMed

    Sun, Xun; Zhang, Xin-Na; Zhu, Shang-Quan; Zheng, Han-Qi

    2000-01-01

    Divalent cations, Ca(2 ), Mg(2 ) and Mn(2 ) enhance the binding of bream growth hormone (brGH) to snakehead fish liver membrane, and their optimum concentration was found to be 8 12 mmol/L, at which Ca(2 ), Mg(2 ) and Mn(2 ) could increase, respectively, the specific binding to 230%, 180%, and 200%, compared with the binding in the absence of ions. The Eadie-Scatchard plot was used for the dynamic analysis of the Ca(2 ) binding site. A low affinity Ca(2 ) binding site was found in the GH-receptor complex with K(m)=0.384 mmol/L, and the affinity constant (K(a)) was increased from 1.045x10(9) L.mol(-1) to 1.295x10(9) L.mol(-1) by the addition of 10 mmol/L CaCl(2). The effects of disulfide bond reducing agents, DTT and ME, on (125)I-brGH binding to growth hormone receptor (GHR) on snakehead fish liver memebrane were also analyzed. The addition of 0.1 20 mmol/L DTT or 0.01% 1% ME to the radioreceptor assay system caused a significant dose dependent increase in the specific binding for (125)I-brGH. In the presence of 0.8 mmol/L DTT or 0.08% ME, the specific binding of (125)I-brGH was increased from 10.2% to 15.5% and 13.2% respectively, and the affinity constant was also increased from 1.265x10(9) L.mol(-1) to 2.185x10(9) L.mol(-1) and 1.625x10(9) L.mol(-1), respectively but no changes in the binding capacity were observed. Further studies showed that the effects of reductants on the specific binding of brGH were due in part to the ligand itself and in part to GHR. In addition, it was observed that one of the three disulfide bonds of brGH could be reduced by 0.8 mmol/L DTT.

  4. Structure, mapping and expression of a growth factor inducible gene encoding a putative nuclear hormonal binding receptor.

    PubMed Central

    Ryseck, R P; Macdonald-Bravo, H; Mattéi, M G; Ruppert, S; Bravo, R

    1989-01-01

    We have characterized a growth factor inducible gene, N10, encoding a nuclear protein of 601 amino acids with a significant similarity to members of the steroid and thyroid hormone receptor families. The gene is rapidly but transiently induced by several mitogens. Immunoprecipitation studies show that the N10 protein is transiently expressed after stimulation of quiescent cells, presenting a half-life of approximately 30 min. The N10 transcription unit is 8 kb in length, split into seven exons. The exon-intron distribution is in general similar to that of other members of the nuclear receptor superfamily, but presents some differences which suggest that N10 belongs to a new family of these molecules. The 5' flanking region contains one DSE which could explain its immediate response to external stimulus. The N10 gene is located in the [F1-F3] region of mouse chromosome 15. Images PMID:2555161

  5. Alternatively spliced forms in the cytoplasmic domain of the human growth hormone (GH) receptor regulate its ability to generate a soluble GH-binding protein.

    PubMed Central

    Dastot, F; Sobrier, M L; Duquesnoy, P; Duriez, B; Goossens, M; Amselem, S

    1996-01-01

    The mechanism underlying the generation of soluble growth hormone binding protein (GHBP) probably differs among species. In rats and mice, it involves an alternatively spliced mRNA, whereas in rabbits, it involves limited proteolysis of the membrane-bound growth hormone receptor (GHR). In humans, this latter mechanism is favored, as no transcript coding for a soluble GHR has been detected so far. To test this hypothesis, we analyzed COS-7 cells transiently expressing the full-length human (h) GHR and observed specific GH-binding activity in the cell supernatants. Concomitantly, an alternatively spliced form in the cytoplasmic domain of GHR, hGHR-tr, was isolated from several human tissues. hGHR-tr is identical in sequence to hGHR, except for a 26-bp deletion leading to a stop codon at position 280, thereby truncating 97.5% of the intracellular domain of the receptor protein. When compared with hGHR, hGHR-tr showed a significantly increased capacity to generate a soluble GHBP. Interestingly, this alternative transcript is also expressed in liver from rabbits, mice, and rats, suggesting that, in these four species, proteolysis of the corresponding truncated transmembrane GHR is a common mechanism leading to GHBP generation. These findings support the hypothesis that GHBP may at least partly result from alternative splicing of the region encoding the intracellular domain and that the absence of a cytoplasmic domain may be involved in increased release of GHBP. Images Fig. 2 Fig. 4 PMID:8855247

  6. Regulation of insulin-like growth factors and their binding proteins by thyroid stimulating hormone in human osteoblast-like (SaOS2) cells.

    PubMed

    Ramajayam, G; Vignesh, R C; Karthikeyan, S; Kumar, K Senthil; Karthikeyan, G D; Veni, S; Sridhar, M; Arunakaran, J; Aruldhas, M Michael; Srinivasan, N

    2012-09-01

    Thyroid stimulating hormone (TSH) is shown to have definite anabolic effects on skeletal metabolism. Previous studies have demonstrated that Insulin-like growth factors (IGF-I and IGF-II) and their six high affinity binding proteins (IGFBPs 1-6) regulate proliferation and differentiation of bone-forming osteoblasts. The current study was intended to determine whether the anabolic effects of TSH on human osteoblastic (SaOS2) cells are mediated through insulin-like growth factor system components. TSH given at 0.01 ng to 10 ng/ml dose levels for 24 and 48 h significantly increased human osteoblastic (SaOS2) cell proliferation and alkaline phosphatase activity, the differentiation marker. TSH significantly increased IGFs (IGF-I and IGF-II) mRNA expression after 6 and 24 h and their protein levels after 24 and 48 h of treatment, respectively. Unlike the IGFs, the IGFBPs responded differently to TSH treatment. Though there were some inconsistencies in the regulation of stimulatory IGF binding protein-3 and -5 by TSH treatment, there was an overall increase at the mRNA abundance and protein levels. Again, the inconsistency persisted at the regulation of the inhibitory IGFBPs 2, 4, and 6 especially at the level of mRNA expression due to TSH treatment, there is an overall decrease in the levels of IGFBP-2, 4, and 6 in the conditioned media (CM) of SaOS2 cell cultures. The IGFBP proteases which control the availability of IGFs are also regulated by hormones. Pregnancy-Associated Plasma Protein-A (PAPP-A) is responsible for the proteolysis of IGFBP-4. TSH treatment significantly unregulated the expression of PAPP-A both at mRNA and protein levels. In conclusion, TSH promotes human osteoblastic (SaOS2) cell proliferation and differentiation by upregulating IGFs and their stimulatory IGF binding proteins and down regulating the inhibitory IGF binding proteins.

  7. Growth hormone stimulation test - series (image)

    MedlinePlus

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. ... performed on infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. ...

  8. Genetics Home Reference: isolated growth hormone deficiency

    MedlinePlus

    ... Health Conditions isolated growth hormone deficiency isolated growth hormone deficiency Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Isolated growth hormone deficiency is a condition caused by a severe ...

  9. Enzyme immunoassay for rat growth hormone: applications to the study of growth hormone variants

    SciTech Connect

    Farrington, M.A.; Hymer, W.C.

    1987-06-29

    A sensitive and specific competitive enzyme immunoassay (EIA) for rat growth hormone was developed. In this assay soluble growth hormone and growth hormone adsorbed to a solid-phase support compete for monkey anti-growth hormone antibody binding sites. The immobilized antibody-growth hormone complex is detected and quantified using goat anti-monkey immunoglobin G covalently conjugated to horse radish peroxidase. Therefore, a high concentration of soluble growth hormone in the sample will result in low absorbance detection from the colored products of the enzyme reaction. Assay parameters were optimized by investigating the concentration of reagents and the reaction kinetics in each of the assay steps. The assay can be performed in 27 hours. A sensitivity range of 0.19 ng to 25 ng in the region of 10 to 90% binding was obtained. Near 50% binding (3 ng) the intraassay coefficient of variation (CV) was 5.54% and the interassay CV was 5.33%. The correlation coefficient (r/sup 2/) between radioimmunoassay and EIA was 0.956 and followed the curve Y = 0.78X + 1.0. 9 references, 6 figures.

  10. Order effects of combined strength and endurance training on testosterone, cortisol, growth hormone, and IGF-1 binding protein 3 in concurrently trained men.

    PubMed

    Rosa, Claudio; Vilaça-Alves, José; Fernandes, Helder M; Saavedra, Francisco J; Pinto, Ronei S; dos Reis, Victor M

    2015-01-01

    Concurrent training (CT) has been widely used in fitness centers to simultaneously optimize cardiovascular and neuromuscular fitness, and induce a high-energy expenditure. Therefore, the aim of this study was to compare the acute effects of 2 different orders of CT on hormonal responses in concurrently trained men. Fourteen men (mean ± SD: 24.7 ± 5.1 years) were randomly divided into 2 groups: endurance training followed by strength (ES, n = 7) and strength training followed by endurance (SE, n = 7). Serum concentrations of testosterone, cortisol, growth hormone, and IGF-1 binding protein 3 (IGFBP-3) were measured before and after both training orders. A significant interaction between exercise order and time was only found in the IGFBP-3 levels (p = 0.022). The testosterone and IGFBP-3 concentrations significantly increased in the ES group after the exercise trainings (57.7 ± 35.1%, p = 0.013 and 17.0 ± 15.5%, p = 0.032, respectively) but did not change significantly in the SE group (15.5 ± 36.6%, p = 0.527 and -4.2 ± 13.9%, p = 0.421, respectively). Conversely, cortisol and growth hormone concentrations significantly increased in both ES (169.2 ± 191.0%, p = 0.021 and 13,296.8 ± 13,009.5%, p = 0.013, respectively) and SE (92.2 ± 81.5%, p = 0.017 and 12,346.2 ± 9714.1%, p = 0.001, respectively) groups compared with baseline values. No significant correlations were found between the changes in the hormonal concentrations. In conclusion, these results suggest that immediately postexercise testosterone and IGFPB-3 responses are significantly increased only after the ES order. Therefore, an ES training order should be prescribed if the main focus of the training intervention is to induce an acute postexercise anabolic environment.

  11. Growth Hormone-Releasing Hormone in Diabetes

    PubMed Central

    Fridlyand, Leonid E.; Tamarina, Natalia A.; Schally, Andrew V.; Philipson, Louis H.

    2016-01-01

    Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggest that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications. PMID:27777568

  12. Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS).

    PubMed

    López-Guerra, A; Chirino, R; Navarro, D; Fernández, L; Boada, L D; Zumbado, M; Díaz-Chico, B N

    1997-01-01

    Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiological concentrations to increase the LAGS level. Since female rats show a LAGS level that is much lower than the males (0.15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect was reversed by implanting a Sylastic capsule containing testosterone. When the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level decreased from 23 to 0.2 pmol/mg protein. This effect was not observed in intact male rats and can be partially reversed by testosterone implants into OX rats. Both hypophysectomized male rats and hypothyroid-orchiectomized male rats showed very low levels of LAGS. Administration of physiological doses of GH and/or T3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T3, and significantly decreased the response to hGH, and to a combination of hGH and T3. These results suggest that physiological estradiol levels can antagonize the LAGS induction by T3 and hGH in the male rat, and could be responsible for the low level of LAGS in the female rat. Moreover, estrogen capsules also inhibited the increase in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T3 and/or GH.

  13. Short stature associated with high circulating insulin-like growth factor (IGF)-binding protein-1 and low circulating IGF-II: effect of growth hormone therapy.

    PubMed

    Barreca, A; Bozzola, M; Cesarone, A; Steenbergh, P H; Holthuizen, P E; Severi, F; Giordano, G; Minuto, F

    1998-10-01

    We report a case of short stature associated with high circulating levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-10 and low levels of IGF-II responsive to pharmacological treatment with GH. Our patient suffered severe growth failure from birth (2.06 SD below the mean for normal full-term boys, and 5.2 and 7.3 SD below the mean at 5 and 10 months). Studies carried out before referral to our pediatric unit included normal 46,XY karyotype and normal encephalic imaging. Other endocrine and metabolic alterations and other systemic diseases were excluded. At 1.7 yr of age (length, 6.1 SD; weight, 4.6 SD; head circumference, 1.4 SD below the mean, respectively) the patient was referred to our pediatric unit. The baseline GH concentration was 31 microg/L, and the peak after an arginine load was 59.6 microg/L. In the same samples GH bioactivity was nearly superimposable (RIA/Nb2 bioactivity ratio = 0.9). Fasting insulin and glucose concentrations were 7.4 microU/mL and 65 mg/dL, respectively, both normally responsive to an oral glucose load. GH insensitivity was excluded by a basal IGF-I concentration (64 ng/mL) in the normal range for 0- to 5-yr-old boys and its increase after 2 IU/day hGH administration for 4 days. IGFBP-3 (0.5 microg/mL) was slightly reduced, whereas IGFBP-1 (2218 and 1515 ng/mL in two different basal samples) was well above the normal values for age and was suppressible by GH (maximum suppression, -77% at 84 h) and glucose load (maximum suppression, -46% at 150 min). The basal IGF-II concentration was below the normal range (86 ng/mL), whereas IGFBP-2 was normal (258 ng/mL). Analysis of the promoter region of IGFBP-1 and IGF-II failed to find major alterations. Neutral gel filtration of serum showed that almost all IGF-I activity was in the 35- to 45-kDa complex, coincident with IGFBP-1 peak, while the 150-kDa complex was absent, although the acid-labile subunit was normally represented. At 2.86 yr (height, 65.8 cm; height SD score

  14. Sex hormone-related and growth hormone-related alopecias.

    PubMed

    Schmeitzel, L P

    1990-11-01

    Canine endocrine dermatoses are characterized by bilateral symmetrical alopecia. Although growth hormone-related and sex hormone-related dermatoses are less common than hypothyroidism and hyperadrenocorticism, they are important causes of hormonal skin disease. Several new syndromes associated with growth and sex hormones recently have been described.

  15. Prokaryotic soluble overexpression and purification of bioactive human growth hormone by fusion to thioredoxin, maltose binding protein, and protein disulfide isomerase.

    PubMed

    Nguyen, Minh Tan; Koo, Bon-Kyung; Thi Vu, Thu Trang; Song, Jung-A; Chong, Seon-Ha; Jeong, Boram; Ryu, Han-Bong; Moh, Sang-Hyun; Choe, Han

    2014-01-01

    Human growth hormone (hGH) is synthesized by somatotroph cells of the anterior pituitary gland and induces cell proliferation and growth. This protein has been approved for the treatment of various conditions, including hGH deficiency, chronic renal failure, and Turner syndrome. Efficient production of hGH in Escherichia coli (E. coli) has proven difficult because the E. coli-expressed hormone tends to aggregate and form inclusion bodies, resulting in poor solubility. In this study, seven N-terminal fusion partners, hexahistidine (His6), thioredoxin (Trx), glutathione S-transferase (GST), maltose-binding protein (MBP), N-utilization substance protein A (NusA), protein disulfide bond isomerase (PDI), and the b'a' domain of PDI (PDIb'a'), were tested for soluble overexpression of codon-optimized hGH in E. coli. We found that MBP and hPDI tags significantly increased the solubility of the hormone. In addition, lowering the expression temperature to 18°C also dramatically increased the solubility of all the fusion proteins. We purified hGH from MBP-, PDIb'a'-, or Trx-tagged hGH expressed at 18°C in E. coli using simple chromatographic techniques and compared the final purity, yield, and activity of hGH to assess the impact of each partner protein. Purified hGH was highly pure on silver-stained gel and contained very low levels of endotoxin. On average, ∼37 mg, ∼12 mg, and ∼7 mg of hGH were obtained from 500 mL-cell cultures of Trx-hGH, MBP-hGH, and PDIb'a'-hGH, respectively. Subsequently, hGH was analyzed using mass spectroscopy to confirm the presence of two intra-molecular disulfide bonds. The bioactivity of purified hGHs was demonstrated using Nb2-11 cell.

  16. Prokaryotic soluble overexpression and purification of bioactive human growth hormone by fusion to thioredoxin, maltose binding protein, and protein disulfide isomerase.

    PubMed

    Nguyen, Minh Tan; Koo, Bon-Kyung; Thi Vu, Thu Trang; Song, Jung-A; Chong, Seon-Ha; Jeong, Boram; Ryu, Han-Bong; Moh, Sang-Hyun; Choe, Han

    2014-01-01

    Human growth hormone (hGH) is synthesized by somatotroph cells of the anterior pituitary gland and induces cell proliferation and growth. This protein has been approved for the treatment of various conditions, including hGH deficiency, chronic renal failure, and Turner syndrome. Efficient production of hGH in Escherichia coli (E. coli) has proven difficult because the E. coli-expressed hormone tends to aggregate and form inclusion bodies, resulting in poor solubility. In this study, seven N-terminal fusion partners, hexahistidine (His6), thioredoxin (Trx), glutathione S-transferase (GST), maltose-binding protein (MBP), N-utilization substance protein A (NusA), protein disulfide bond isomerase (PDI), and the b'a' domain of PDI (PDIb'a'), were tested for soluble overexpression of codon-optimized hGH in E. coli. We found that MBP and hPDI tags significantly increased the solubility of the hormone. In addition, lowering the expression temperature to 18°C also dramatically increased the solubility of all the fusion proteins. We purified hGH from MBP-, PDIb'a'-, or Trx-tagged hGH expressed at 18°C in E. coli using simple chromatographic techniques and compared the final purity, yield, and activity of hGH to assess the impact of each partner protein. Purified hGH was highly pure on silver-stained gel and contained very low levels of endotoxin. On average, ∼37 mg, ∼12 mg, and ∼7 mg of hGH were obtained from 500 mL-cell cultures of Trx-hGH, MBP-hGH, and PDIb'a'-hGH, respectively. Subsequently, hGH was analyzed using mass spectroscopy to confirm the presence of two intra-molecular disulfide bonds. The bioactivity of purified hGHs was demonstrated using Nb2-11 cell. PMID:24614134

  17. Relation of exploratory behavior of rats in elevated plus-maze to brain receptor binding properties and serum growth hormone levels.

    PubMed

    Kõks, S; Vasar, E; Soosaar, A; Lang, A; Volke, V; Võikar, V; Bourin, M; Männistö, P T

    1997-11-01

    Forty-five male Wistar rats were selected according to their behavior in the elevated plus-maze. They were separated as follows: animals with low exploratory activity ('anxious'), an 'intermediate' group and animals having high exploratory activity ('non-anxious'). Various receptor binding studies and hormonal assays were also performed in these selected rats. The affinity of 5-hydroxytryptamine 5-HT2A receptors in the frontal cortex was lower in the 'anxious' rats compared to home-cage controls and 'non-anxious' animals. Moreover, the number of cholecystokinin (CCK) receptors in the hippocampus was significantly elevated in the 'anxious' group compared to home-cage control animals. The blood levels of growth hormone (GH) were significantly lower in the 'non-anxious' rats compared to 'anxious' counterparts. In conclusion, it seems likely that the decreased exploratory activity of rats is related to the increased 5-hydroxytryptamine (5-HT) and CCK mediated neurotransmission in the brain. The different serum levels of GH in the selected rats probably reflect alterations in the activity of 5-HT and CCK.

  18. The growth hormone receptor: mechanism of activation and clinical implications.

    PubMed

    Brooks, Andrew J; Waters, Michael J

    2010-09-01

    Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors. PMID:20664532

  19. Pathology of growth hormone excess.

    PubMed

    Kovacs, K

    1988-09-01

    This paper briefly reviews the pathology of growth hormone excess. Prolonged oversecretion of growth hormone is associated with elevated serum growth hormone as well as somatomedian C levels and the clinical signs and symptoms of acromegaly or gigantism. Morphologic studies, including immunohistochemistry and electron microscopy, revealed that several distinct morphologic lesions can be present in the pituitary gland of patients with acromegaly or gigantism. Although substantial progress has been achieved during the last two decades, more work is required to correlate the morphologic features of adenoma cells with their biologic behavior. We feel that the future can be viewed with optimism and further exciting results can be expected by the interaction of pathologists, clinical endocrinologists and basic scientists. PMID:3070506

  20. Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse

    SciTech Connect

    Sanchez-Jimenez, F.; Fielder, P.J.; Martinez, R.R.; Smith, W.C.; Talamantes, F. )

    1990-02-01

    ({sup 125}I)Iodomouse GH (({sup 125}I)iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse.

  1. Growth Hormone and Cerebral Amyloidosis.

    PubMed

    Benvenga, S; Guarneri, F

    2016-08-01

    Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer's disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer's disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers' pituitaries, may have led to the observed co-occurring of Creutzfeldt-Jakob disease and Alzheimer's disease. PMID:27214308

  2. Growth Hormone: Use and Abuse

    MedlinePlus

    ... than children of the same age), such as chronic kidney disease, Turner syndrome, and Prader-Willi syndrome In adults, GH is used to treat • Growth hormone deficiency • Muscle wasting (loss of muscle tissue) from HIV • Short bowel ...

  3. Aetiology of growth hormone deficiency.

    PubMed Central

    Herber, S M; Kay, R

    1987-01-01

    A retrospective analysis was performed in an attempt to identify perinatal risk factors for the development of growth hormone deficiency. More of the affected children were boys, and their birth weights were significantly lower than those of the national average; there were also considerably more preterm and post-term deliveries among boys. PMID:3632025

  4. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  5. Growth hormone in musculoskeletal pain states.

    PubMed

    Bennett, Robert

    2004-08-01

    Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is increasing appreciation that suboptimal growth hormone secretion, leading to a state of adult growth hormone deficiency, may occur in the setting of chronic inflammatory disease, chronic corticosteroid use, and fibromyalgia. Therefore, the evaluation and effective management of growth hormone oversecretion and undersecretion is relevant to practicing rheumatologists. PMID:15251074

  6. Growth hormone and its disorders.

    PubMed

    Ayuk, J; Sheppard, M C

    2006-01-01

    Growth hormone (GH) is synthesised and secreted by the somatotroph cells of the anterior lobe of the pituitary gland. Its actions involve multiple organs and systems, affecting postnatal longitudinal growth as well as protein, lipid, and carbohydrate metabolism. GH hypersecretion results in gigantism or acromegaly, a condition associated with significant morbidity and mortality, while GH deficiency results in growth retardation in children and the GH deficiency syndrome in adults. This article, aimed at non-paediatric physicians, examines the clinical features, diagnosis, and current concepts in the management of these conditions. PMID:16397076

  7. Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

    PubMed

    Yoshida, T; Shimatsu, A; Sakane, N; Hizuka, N; Horikawa, R; Tanaka, T

    1996-01-01

    We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism. PMID:8550769

  8. Identification of a new hormone-binding site on the surface of thyroid hormone receptor.

    PubMed

    Souza, P C T; Puhl, A C; Martínez, L; Aparício, R; Nascimento, A S; Figueira, A C M; Nguyen, P; Webb, P; Skaf, M S; Polikarpov, I

    2014-04-01

    Thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily of ligand-activated transcription factors involved in cell differentiation, growth, and homeostasis. Although X-ray structures of many nuclear receptor ligand-binding domains (LBDs) reveal that the ligand binds within the hydrophobic core of the ligand-binding pocket, a few studies suggest the possibility of ligands binding to other sites. Here, we report a new x-ray crystallographic structure of TR-LBD that shows a second binding site for T3 and T4 located between H9, H10, and H11 of the TRα LBD surface. Statistical multiple sequence analysis, site-directed mutagenesis, and cell transactivation assays indicate that residues of the second binding site could be important for the TR function. We also conducted molecular dynamics simulations to investigate ligand mobility and ligand-protein interaction for T3 and T4 bound to this new TR surface-binding site. Extensive molecular dynamics simulations designed to compute ligand-protein dissociation constant indicate that the binding affinities to this surface site are of the order of the plasma and intracellular concentrations of the thyroid hormones, suggesting that ligands may bind to this new binding site under physiological conditions. Therefore, the second binding site could be useful as a new target site for drug design and could modulate selectively TR functions.

  9. CCAAT-enhancer-binding Protein β (C/EBPβ) and Downstream Human Placental Growth Hormone Genes Are Targets for Dysregulation in Pregnancies Complicated by Maternal Obesity*

    PubMed Central

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A.

    2013-01-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in “normal” pregnancy. Maternal obesity can exacerbate this “resistance,” suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m2) versus lean (BMI 20–25 kg/m2) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development. PMID:23782703

  10. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity.

    PubMed

    Vakili, Hana; Jin, Yan; Menticoglou, Savas; Cattini, Peter A

    2013-08-01

    Human chorionic somatomammotropin (CS) and placental growth hormone variant (GH-V) act as metabolic adaptors in response to maternal insulin resistance, which occurs in "normal" pregnancy. Maternal obesity can exacerbate this "resistance," suggesting that CS, GH-V, or transcription factors that regulate their production might be targets. The human CS genes, hCS-A and hCS-B, flank the GH-V gene. A significant decrease in pre-term placental CS/GH-V RNA levels was observed in transgenic mice containing the CS/GH-V genes in a model of high fat diet (HFD)-induced maternal obesity. Similarly, a decrease in CS/GH-V RNA levels was detected in term placentas from obese (body mass index (BMI) ≥ 35 kg/m(2)) versus lean (BMI 20-25 kg/m(2)) women. A specific decrease in transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) RNA levels was also seen with obesity; C/EBPβ is required for mouse placenta development and is expressed, like CS and GH-V, in syncytiotrophoblasts. Binding of C/EBPβ to the CS gene downstream enhancer regions, which by virtue of their position distally flank the GH-V gene, was reduced in placenta chromatin from mice on a HFD and in obese women; a corresponding decrease in RNA polymerase II associated with CS/GH-V promoters was also observed. Detection of decreased endogenous CS/GH-V RNA levels in human placental tumor cells treated with C/EBPβ siRNA is consistent with a direct effect. These data provide evidence for CS/GH-V dysregulation in acute HFD-induced obesity in mouse pregnancy and chronic obesity in human pregnancy and implicate C/EBPβ, a factor associated with CS regulation and placental development.

  11. Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency

    PubMed Central

    Janukonyté, Jurgita; Klose, Marianne; Marina, Djordje; Tanvig, Mette; Nielsen, Lene F.; Höybye, Charlotte; Andersen, Marianne; Feldt-Rasmussen, Ulla; Christiansen, Jens Sandahl

    2016-01-01

    Context: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. Objectives: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH. Design and Setting: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. Patients: Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. Interventions and Main Outcome Measures: Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies. Results: Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0–168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group. Conclusion: Four once-weekly doses of NNC0195-0092 (dose range 0.02–0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated

  12. A Simulated Growth Hormone Analysis

    NASA Astrophysics Data System (ADS)

    Harris, Mary

    1996-08-01

    Growth hormone is a drug that is sometimes abused by amateur or professional athletes for performance-enhancement. This laboratory is a semimicroscale simulation analysis of a sample of "urine" to detect proteins of two very different molecular weights. Gel filtration uses a 10 mL disposable pipette packed with Sephadex. Students analyze the fractions from the filtration by comparing colors of the Brilliant Blue Coomassie Dye as it interacts with the proteins in the sample to a standard set of known concentration of protein with the dye. The simulated analysis of growth hormone is intended to be included in a unit on organic chemistry or in the second year of high school chemistry.

  13. The growth hormone secretagogue receptor.

    PubMed

    Cruz, Conrad Russell Young; Smith, Roy G

    2008-01-01

    The neuroendocrine hormone ghrelin, a recently discovered acylated peptide with numerous activities in various organ systems, exerts most of its known effects on the body through a highly conserved G-protein-coupled receptor, the growth hormone secretagogue receptor (GHSR) type 1a. The GHSR's wide expression in different tissues reflects activity of its ligands in the hypothalamic-pituitary, cardiovascular, immune, gastrointestinal, and reproductive systems. Its extensive cellular distribution along with its important actions on the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and other neuroendocrine and metabolic systems suggest a pivotal role in governing the mechanisms of aging. A more comprehensive characterization of the receptor, and a more thorough identification of its various agonists and antagonists, will undoubtedly introduce important clinical applications in age-related states like anorexia, cardiovascular pathology, cancer, impaired energy balance, and immune dysfunction. Although present knowledge points to a single functional receptor and a single endogenous ligand, recent investigations suggest the existence of additional GHSR subtypes, as well as other endogenous agonists. It has been more than a decade since the landmark cloning of this ubiquitous, highly conserved receptor, and the considerable extent of its effects on normal physiology and disease states have filled the literature with incredible insights on how organisms regulate various functions through subtle signaling processes. But science has barely scratched the surface, and we can be assured that the mysteries surrounding the precise nature of ghrelin and its receptor(s) are only beginning to unravel. PMID:17983853

  14. Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4.

    PubMed

    Donahue, L R; Beamer, W G

    1993-01-01

    Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments--water, fat, protein and mineral--are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38-130 micrograms/l) compared with normal lit/+ littermates (range 432-567 micrograms/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat

  15. Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

    SciTech Connect

    Nivot, S.; Adan, L.; Souberbielle, J.; Rappaport, R.; Brauner, R.; Benelli, C.; Clot, J.P.; Saucet, C.; Zucker, J.M.

    1994-03-01

    The authors studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 {+-} 9.0 ng/mL, 1.1 {+-} 0.2 {mu}g/mL, and 7.6 {+-} 3.3% of radioactivity as compared to time 0 values: 139 {+-} 15 ng/mL, 2.2 {+-} 0.2 {mu}g/mL, and 20.0 {+-} 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient they observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients. 28 refs., 4 figs., 1 tab.

  16. Control of growth hormone synthesis.

    PubMed

    Tuggle, C K; Trenkle, A

    1996-01-01

    A large body of research, primarily in the rodent and human species, has elucidated many of the details regarding the control of GH synthesis and release. Cell type-specific transcriptional control has been identified as the main mechanism of the somatotroph-specific expression of GH. The recent detailed analysis in rodents and humans of a highly specific transcriptional activator protein, PIT-1, has opened several new areas of study. This is especially true for research in the farm animal species, where PIT-1 has been cloned and its binding elements on the GH gene are being investigated in a number of economically important species. Genetic and biochemical analyses of PIT-1 and other GH regulators have shown the central role of PIT-1 not only in the cell-autonomous stimulation of GH gene transcription, but also in the participation of PIT-1 in the response at the GH gene to exogenous hormones such as RA and TH. PIT-1 has been implicated in the proliferative development of the pituitary itself, in the maintenance of anterior pituitary cell types once cell types are defined, and in the mechanism by which the hypothalamic signal for GH release is transduced. However, PIT-1 by itself does not activate the GH gene, so that additional unknown factors exist that need to be identified to fully understand the cell type-specific activation of the GH gene. In addition, GH gene regulatory elements acting through well-characterized systems such as TH have seemingly different effects; the specific context of the regulatory elements relative to the promoter elements appear to be crucial. These contextual details of GH gene regulation are not well understood for any species and need to be further studied to be able to make predictions for particular elements and regulatory mechanisms across species. The regulation of the pulsatile secretion of GH by GHRH and SRIH is reasonably well understood after the cloning and analysis of the two releasing factors and their receptors

  17. [Laboratory diagnosis of growth hormone].

    PubMed

    Macchia, V; Mariano, A

    1993-09-01

    The role of Clinical Pathology Laboratory in normal and altered growth hormone secretion is discussed. In particular, it is reported that the normal GH secretion can be studied by serum and urine GH determinations whereas the diagnosis of GH deficiency rests upon the demonstration of an inadequate rise serum GH after provocative stimuli and serum measurement of somatomedins (IGF-I) by radioimmunoassay method. As it concerns increase GH secretion the diagnosis is clinically made (acromegaly and gigantism) and the laboratory has only the role to confirm it by the assessment of basal and stimulated GH secretion. PMID:7910655

  18. Growth hormone deficiency: an update.

    PubMed

    Audí, L; Fernández-Cancio, M; Camats, N; Carrascosa, A

    2013-03-01

    Growth hormone (GH) deficiency (GHD) in humans manifests differently according to the individual developmental stage (early after birth, during childhood, at puberty or in adulthood), the cause or mechanism (genetic, acquired or idiopathic), deficiency intensity and whether it is the only pituitary-affected hormone or is combined with that of other pituitary hormones or forms part of a complex syndrome. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise mutation types and mechanisms for previously described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic, although less frequently when they are congenital and/or familial. The clinical and biochemical diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, probably because the diagnosis based on the so-called GH secretion stimulation tests will prove to be of limited usefulness for predicting therapy indications.

  19. An enzyme immunoassay for rat growth hormone - Applications to the study of growth hormone variants

    NASA Technical Reports Server (NTRS)

    Farrington, Marianne A.; Hymer, W. C.

    1987-01-01

    A sensitive and specific competitive enzyme immunoassay for rat growth hormone (GH) is described and its use in the detection of GH variants is demonstrated. In the present assay, soluble GH and GH adsorbed to a solid-phase support compete for monkey anti-GH antibody binding sites. The immobilized antibody-GH complex is detected and quantified using goat antimonkey immunoglobin G covalently conjugated to horseradish peroxidase. It is noted that the assay can be performed in 27 hours and that sensitivities in the range of 0.19 to 25 ng can be obtained in the region of 10 to 90 percent binding.

  20. Growth Hormone and Craniofacial Tissues. An update

    PubMed Central

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

  1. Determinants of Growth Hormone Resistance in Malnutrition

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    States of under-nutrition are characterized by growth hormone resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies result in elevated growth hormone levels and low levels of IGF-I. We review various states of malnutrition and a disease state characterized by chronic under-nutrition -- anorexia nervosa -- and discuss possible mechanisms contributing to the state of growth hormone resistance, including FGF-21 and SIRT1. We conclude by examining the hypothesis that growth hormone resistance is an adaptive response to states of under-nutrition, in order to maintain euglycemia and preserve energy. PMID:24363451

  2. [Plant hormones, plant growth regulators].

    PubMed

    Végvári, György; Vidéki, Edina

    2014-06-29

    Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

  3. [Plant hormones, plant growth regulators].

    PubMed

    Végvári, György; Vidéki, Edina

    2014-06-29

    Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life. PMID:24954142

  4. Growth hormone doping: a review

    PubMed Central

    Erotokritou-Mulligan, Ioulietta; Holt, Richard IG; Sönksen, Peter H

    2011-01-01

    The use of growth hormone (GH) as a performance enhancing substance was first promoted in lay publications, long before scientists fully acknowledged its benefits. It is thought athletes currently use GH to enhance their athletic performance and to accelerate the healing of sporting injuries. Over recent years, a number of high profile athletes have admitted to using GH. To date, there is only limited and weak evidence for its beneficial effects on performance. Nevertheless the “hype” around its effectiveness and the lack of a foolproof detection methodology that will detect its abuse longer than 24 hours after the last injection has encouraged its widespread use. This article reviews the current evidence of the ergogenic effects of GH along with the risks associated with its use. The review also examines methodologies, both currently available and in development for detecting its abuse. PMID:24198576

  5. Neuroprotective Actions of Ghrelin and Growth Hormone Secretagogues

    PubMed Central

    Frago, Laura M.; Baquedano, Eva; Argente, Jesús; Chowen, Julie A.

    2011-01-01

    The brain incorporates and coordinates information based on the hormonal environment, receiving information from peripheral tissues through the circulation. Although it was initially thought that hormones only acted on the hypothalamus to perform endocrine functions, it is now known that they in fact exert diverse actions on many different brain regions including the hypothalamus. Ghrelin is a gastric hormone that stimulates growth hormone secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, growth hormone secretagogues–GH secretagogue-receptor, which is most highly expressed in the pituitary and hypothalamus. In addition, ghrelin has effects on learning and memory, reward and motivation, anxiety, and depression, and could be a potential therapeutic agent in neurodegenerative disorders where excitotoxic neuronal cell death and inflammatory processes are involved. PMID:21994488

  6. Growth and growth hormone: An overview.

    PubMed

    Teran, Enrique; Chesner, Jaclyn; Rapaport, Robert

    2016-06-01

    Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure, could be indications of illnesses such as chronic disease, nutritional deficits, celiac disease or hormonal abnormalities. Therefore, a careful assessment of the various requirements for normal growth needs to be done by history, physical examination, and screening laboratory tests. More details will be reviewed about the GH-IGF axis, its abnormalities with special emphasis on GH deficiency, its diagnosis and treatment. GH treatment indications in the US will be reviewed and a few only will be highlighted. They will include GH deficiency, as well as the treatment of children born SGA, including the results of a US study using FDA approved dose of 0.48mg/kg/week. GH deficiency in adults will also be briefly reviewed. Treatment of patients with SHOX deficiency will also be discussed. Possible side effects of GH treatment and the importance of monitoring safety will be highlighted. PMID:26936284

  7. Growth hormone insensitivity syndrome: unusual oral manifestations.

    PubMed

    Borges, Alvaro Henrique; Siqueira, Carlos Rodrigo Barros; Pedro, Fábio Luis Miranda; Palma, Vinícius Canavarros; Sakai, Vivien Thiemy; Volpato, Luiz Evaristo Ricci

    2013-01-01

    Children with significant growth retardation and normal levels of growth hormone are diagnosed with growth hormone insensitivity. The main oral findings observed in patients with growth hormone insensitivity syndrome (GHIS) are underdeveloped jaws, crowded teeth and delayed eruption of permanent teeth. This manuscript describes a 9-year-old child diagnosed with GHIS, who had delayed eruption of permanent teeth and 14 unerupted supernumerary teeth. All supernumerary teeth were extracted except for two maxillary and one mandibular teeth which were difficult to identify and access. Multiple supernumerary teeth have never been reported before in patients with GHIS.

  8. Sex steroids and growth hormone interactions.

    PubMed

    Fernández-Pérez, Leandro; de Mirecki-Garrido, Mercedes; Guerra, Borja; Díaz, Mario; Díaz-Chico, Juan Carlos

    2016-04-01

    GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of sex hormones on the liver may be direct, through hepatic receptors, or indirect by modulating endocrine, metabolic, and gender-differentiated functions of GH. Sex hormones can modulate GH actions by acting centrally, regulating pituitary GH secretion, and peripherally, by modulating GH signaling pathways. The endocrine and/or metabolic consequences of long-term exposure to sex hormone-related compounds and their influence on the GH-liver axis are largely unknown. A better understanding of these interactions in physiological and pathological states will contribute to preserve health and to improve clinical management of patients with growth, developmental, and metabolic disorders.

  9. Recombinant Bovine Growth Hormone Criticism Grows.

    ERIC Educational Resources Information Center

    Gaard, Greta

    1995-01-01

    Discusses concerns related to the use of recombinant bovine growth hormone in the United States and other countries. Analyses the issue from the perspectives of animal rights, human health, world hunger, concerns of small and organic farmers, costs to the taxpayer, and environmental questions. A sidebar discusses Canadian review of the hormone.…

  10. Obesity, growth hormone and exercise.

    PubMed

    Thomas, Gwendolyn A; Kraemer, William J; Comstock, Brett A; Dunn-Lewis, Courtenay; Maresh, Carl M; Volek, Jeff S

    2013-09-01

    Growth hormone (GH) is regulated, suppressed and stimulated by numerous physiological stimuli. However, it is believed that obesity disrupts the physiological and pathological factors that regulate, suppress or stimulate GH release. Pulsatile GH has been potently stimulated in healthy subjects by both aerobic and resistance exercise of the right intensity and duration. GH modulates fuel metabolism, reduces total fat mass and abdominal fat mass, and could be a potent stimulus of lipolysis when administered to obese individuals exogenously. Only pulsatile GH has been shown to augment adipose tissue lipolysis and, therefore, increasing pulsatile GH response may be a therapeutic target. This review discusses the factors that cause secretion of GH, how obesity may alter GH secretion and how both aerobic and resistance exercise stimulates GH, as well as how exercise of a specific intensity may be used as a stimulus for GH release in individuals who are obese. Only five prior studies have investigated exercise as a stimulus of endogenous GH in individuals who are obese. Based on prior literature, resistance exercise may provide a therapeutic target for releasing endogenous GH in individuals who are obese if specific exercise programme variables are utilized. Biological activity of GH indicates that this may be an important precursor to beneficial changes in body fat and lean tissue mass in obese individuals. However, additional research is needed including what molecular GH variants are acutely released and involved at target tissues as a result of different exercise stimuli and what specific exercise programme variables may serve to stimulate GH in individuals who are obese.

  11. A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.

    PubMed Central

    Duquesnoy, P; Sobrier, M L; Duriez, B; Dastot, F; Buchanan, C R; Savage, M O; Preece, M A; Craescu, C T; Blouquit, Y; Goossens, M

    1994-01-01

    Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions. Images PMID:8137822

  12. Oral manifestations in growth hormone disorders.

    PubMed

    Atreja, Gaurav; Atreja, Shikha Handa; Jain, Nitul; Sukhija, Urvashi

    2012-05-01

    Growth hormone is of vital importance for normal growth and development. Individuals with growth hormone deficiency develop pituitary dwarfism with disproportionate delayed growth of skull and facial skeleton giving them a small facial appearance for their age. Both hyper and hypopituitarism have a marked effect on development of oro-facial structures including eruption and shedding patterns of teeth, thus giving an opportunity to treating dental professionals to first see the signs and symptoms of these growth disorders and correctly diagnose the serious underlying disease. PMID:22629503

  13. Growth, growth hormone and cognitive functions.

    PubMed

    Sartorio, A; Conti, A; Molinari, E; Riva, G; Morabito, F; Faglia, G

    1996-01-01

    The interactions among short stature, growth hormone (GH) and cognitive functions have been extensively studied so far. However, although it seems well established that short stature is associated with cognitive problems, little effort has been made to point out the presence of specific psychological effects related to the different forms of short stature. In 'short normal' children, the presence of a scholastic underachievement seems to suggest that short stature 'itself' might predispose these patients to some of their psychosocial difficulties. The higher incidence of academic failure, in presence of a normal intellectual functioning, has been attributed to environmental and psychosocial factors, including over-protective parents and low self-esteem resulting from the impact of short stature. These problems appear to be common also to other forms of short stature (such as Turner's syndrome) where, however, they are frequently associated with other specific deficits. The in vivo model which might allow, at least in part, better understanding of GH (per se)-dependent effects is represented by GH deficiency (GHD), in which, however, the specific role of GH on psychological functioning is frequently masked by the presence of associated hormonal deficiencies. Children with isolated GHD are reported to have specific educational deficits, in particular learning disability and attention-deficit disorders, which have been tentatively attributed to a compromised intellectual potential. The psychological effects of long-term GH treatment in children with GHD still remain controversial, with some retrospective studies describing a generally beneficial outcome. Since early experiences in school are closely related to success in adult life, the possible implications that GHD during childhood holds during adulthood have been recently considered. Although regional differences have been observed in subgroups of adults with GHD, it seems that these patients have normal cognitive

  14. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  15. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  16. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  17. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  18. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth...

  19. Hormone symphony during root growth and development.

    PubMed

    Garay-Arroyo, Adriana; De La Paz Sánchez, María; García-Ponce, Berenice; Azpeitia, Eugenio; Alvarez-Buylla, Elena R

    2012-12-01

    Hormones regulate plant growth and development in response to external environmental stimuli via complex signal transduction pathways, which in turn form complex networks of interaction. Several classes of hormones have been reported, and their activity depends on their biosynthesis, transport, conjugation, accumulation in the vacuole, and degradation. However, the activity of a given hormone is also dependent on its interaction with other hormones. Indeed, there is a complex crosstalk between hormones that regulates their biosynthesis, transport, and/or signaling functionality, although some hormones have overlapping or opposite functions. The plant root is a particularly useful system in which to study the complex role of plant hormones in the plastic control of plant development. Physiological, cellular, and molecular genetic approaches have been used to study the role of plant hormones in root meristem homeostasis. In this review, we discuss recent findings on the synthesis, signaling, transport of hormones and role during root development and examine the role of hormone crosstalk in maintaining homeostasis in the apical root meristem.

  20. A major thyroid hormone response element in the third intron of the rat growth hormone gene.

    PubMed Central

    Sap, J; de Magistris, L; Stunnenberg, H; Vennström, B

    1990-01-01

    The rat growth hormone (RGH) gene constitutes a well-documented model system for the direct regulation of transcription by thyroid hormones. In order to analyse its interaction with sequences in the RGH gene, we have overproduced the thyroid hormone receptor-alpha (c-erbA) protein using a vaccinia virus expression system. The expressed protein bound T3 and DNA-cellulose with expected affinities, and the major binding site for the receptor protein was found to be located in the third intron of the RGH gene. This site displayed significantly higher affinity for the receptor protein than a previously described thyroid hormone response element (TRE) in the promoter of this gene, and also conferred stronger hormone responsiveness in vivo to a heterologous promoter. The data suggest that this novel TRE plays a major role in the regulation of rat growth hormone gene expression by thyroid hormones. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2155782

  1. Obtaining growth hormone from calf blood

    NASA Technical Reports Server (NTRS)

    Kalchev, L. A.; Ralchev, K. K.; Nikolov, I. T.

    1979-01-01

    The preparation of a growth hormone from human serum was used for the isolation of the hormone from calf serum. The preparation was biologically active - it increased the quantity of the free fatty acids released in rat plasma by 36.4 percent. Electrophoresis in Veronal buffer, ph 8.6, showed the presence of a single fraction having mobility intermediate between that of alpha and beta globulins. Gel filtration through Sephadex G 100 showed an elutriation curve identical to that obtained by the growth hormone prepared from pituitary glands.

  2. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    ERIC Educational Resources Information Center

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  3. Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin.

    PubMed

    Tannenbaum, G S; Bowers, C Y

    2001-02-01

    The class of novel synthetic compounds termed growth hormone secretagogues (GHSs) act in the hypothalamus through, as yet, unknown pathways. We performed physiologic and histochemical studies to further understand how the GHS system interacts with the well-established somatostatin (SRIF)/growth hormone-releasing hormone (GHRH) neuroendocrine system for regulating pulsatile GH secretion. Comparison of the GH-releasing activities of the hexapeptide growth hormone-releasing peptide-6 (GHRP-6) and GHRH administered intravenously to conscious adult male rats showed that the pattern of GH responsiveness to GHRP-6 was markedly time-dependent, similar to that observed with GHRH. Immunoneutralization of endogenous SRIF reversed the blunted GH response to GHRP-6 at trough times, suggesting that GHRP-6 neither disrupts nor inhibits the cyclical release of endogenous hypothalamic SRIF. By striking contrast, passive immunization with anti-GHRH serum virtually obliterated the GH responses to GHRP-6, irrespective of the time of administration. These findings suggest that the GHSs do not act by altering SRIF release but, rather, stimulate GH release via GHRH-dependent pathways. Our dual chromogenic and autoradiographic in situ hybridization experiments revealed that a subpopulation of GHRH mRNA-containing neurons in the arcuate (Arc) nucleus and ventromedial nucleus (VMN) of the hypothalamus expressed the GHS receptor (GHS-R) gene. These results provide strong anatomic evidence that GHSs may directly stimulate GHRH release into hypophyseal portal blood, and thereby influence GH secretion, through interaction with the GHS-R on GHRH- containing neurons. Altogether, these findings support the notion that an additional neuroendocrine pathway may exist to regulate pulsatile GH secretion, possibly through the influence of the newly discovered GHS natural peptide, ghrelin. PMID:11322498

  4. A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors.

    PubMed

    Asa, Sylvia L; Digiovanni, Rebecca; Jiang, Jing; Ward, Megan L; Loesch, Kimberly; Yamada, Shozo; Sano, Toshiaki; Yoshimoto, Katsuhiko; Frank, Stuart J; Ezzat, Shereen

    2007-08-01

    Pituitary tumors are a diverse group of neoplasms that are classified based on clinical manifestations, hormone excess, and histomorphologic features. Those that cause growth hormone (GH) excess and acromegaly are subdivided into morphologic variants that have not yet been shown to have pathogenetic significance or predictive value for therapy and outcome. Here, we identify a selective somatic histidine-to-leucine substitution in codon 49 of the extracellular domain of the GH receptor (GHR) in a morphologic subtype of human GH-producing pituitary tumors that is characterized by the presence of cytoskeletal aggresomes. This GHR mutation significantly impairs glycosylation-mediated receptor processing, maturation, ligand binding, and signaling. Pharmacologic GH antagonism recapitulates the morphologic phenotype of pituitary tumors from which this mutation was identified, inducing the formation of cytoskeletal keratin aggresomes. This novel GHR mutation provides evidence for impaired hormone autofeedback in the pathogenesis of these pituitary tumors. It explains the lack of responsiveness to somatostatin analogue therapy of this tumor type, in contrast to the exquisite sensitivity of tumors that lack aggresomes, and has therapeutic implications for the safety of GH antagonism as a therapeutic modality in acromegaly. PMID:17671221

  5. Growth Hormone Deficiency in Children

    MedlinePlus

    ... many reasons for slow growth and below-average height in children. At times, slow growth is normal ... same age Signs of GHD • Slowed growth in height in infants, children, or adolescents (teenagers) • A young- ...

  6. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    PubMed

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  7. Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers.

    PubMed

    Zoenen, Maxime; Urizar, Eneko; Swillens, Stéphane; Vassart, Gilbert; Costagliola, Sabine

    2012-01-01

    Glycoprotein hormone receptors show strong negative cooperativity. As a consequence, at physiological hormone concentrations, a single agonist binds to a receptor dimer. Here we present evidence that constitutively active receptors lose cooperative allosteric regulation in direct relation with their basal activity. The most constitutive mutants lost nearly all cooperativity and showed an increase of initial tracer binding, reflecting the ability of each protomer to bind with equal affinity. Allosteric interaction between the protomers takes place at the transmembrane domain. The allosteric message resulting from hormone binding to the ectodomain of one protomer travels 'downward' to its transmembrane domain, before affecting the transmembrane domain of the other protomer. This results in transmission of an 'upward' message lowering the binding affinity of the ectodomain of the second protomer. Our results demonstrate a direct relation between the conformational changes associated with activation of the transmembrane domain and the allosteric behaviour of glycoprotein hormone receptors dimers.

  8. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  9. Recombinant-derived chicken growth hormone used for radioimmunoassay

    SciTech Connect

    Proudman, J.A.

    1984-04-01

    The use of recombinant-derived chicken growth hormone (rcGH) in an avian growth hormone (GH) radioimmunoassay (RIA) procedure is described. Antiserum to turkey GH bound /sup 125/I-labeled rcGH, and unlabeled rcGH or turkey GH displaced binding in a dose-related manner. The dose-response curves of sera and pituitary extract from chickens and turkeys were parallel to the rcGH standard curve. Sera from hypophysectomized (hypox) chickens and turkeys produced no dose-response and did not inhibit binding of labeled rcGH. Recovery of rcGH added to hypox sera was quantitative. Modification of the homologous turkey GH RIA protocol of Proudman and Wentworth (1) to use rcGH made possible either an increase in assay sensitivity or a 3-day reduction in incubation time.

  10. Signal transduction by the growth hormone receptor

    SciTech Connect

    Waters, M.J.; Rowlinson, S.W.; Clarkson, R.W.

    1994-12-31

    It has been proposed that dimerization of identical receptor subunits by growth hormone (GH) is the mechanism of signal transduction across the cell membrane. We present here data with analogs of porcine GH (pGH), with GH receptors (GHR) mutated in the dimerization domain and with monoclonal antibodies to the GHR which indicate that dimerization is necessary but not sufficient for transduction. We also report nuclear uptake of GH both in vivo and in vitro, along with nuclear localization of the receptor and GH-binding protein (GHBP). This suggests that GH acts directly at the nucleus, and one possible target for this action is a rapid increase in transcription of C/EBP delta seen in 3T3-F442A cells in response to GH. This tyrosine kinase-dependent event may be an archetype for induction of other immediate early gene transcription factors which then interact to determine the programming of the subsequent transcriptional response to GH. 29 refs., 1 fig., 1 tab.

  11. Inertia of endocrine systems due to hormone binding to circulatory proteins.

    PubMed

    Kurbel, Sven; Zucić, Damir; Kurbel, Beatrica; Gulam, Danijela; Gmajnić, Rudika; Krajina, Zdenko

    2003-03-01

    It is often presumed that the main role of hormone binding to albumins and binding proteins (BPs) is to reduce oscillating levels of free hormone molecules and to transport steroid hormones. This paper is an attempt to define possible consequences of hormone molecules binding to carrier proteins in circulation. Binding to albumins and BPs prevents exact and quick control of hormone actions. Hormones without significant protein binding govern vital and fast acting regulatory mechanisms (blood glucose or calcium) in which any added inertia might be dangerous. In the presented model, the added inertia for a partially bound hormone (H) is defined as: H(bound)/H(free). Values, calculated from the reported data, range from 0.4 for GH to more than 2000 for T(4). In comparison to albumins, high-affinity BPs make more stable reserve that would cover periods of low or no hormone secretion. At the same time, hormone molecules are taken away from the blood level control and thus might be considered sequestrated. For hormones without protein binding, the well-perfused areas of the body, or the areas with increased capillary permeability, would be more exposed, making an uneven distribution among target tissues. For the hormone that binds blood proteins, places of secretion and tissue perfusion become unimportant, since the hormone is being liberated anywhere in the circulation (i.e., for strongly bound IGFs, IGF binding proteins do not just stabilize proinsulin actions of IGF-1, but also make all parts of body to be under the same exposure to liberated IGFs, an important feature to promote a symmetrical bone growth). Estrogens are known to stimulate liver secretion of different BPs. A possible explanation is that in the follicular phase there is a small initial mass of granulosa cells, and it takes time to saturate free estrogen carriers, before the normal free hormone level can be reached and FSH secretion inhibited. Less inert peptide inhibin might suppress FSH before free

  12. Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome.

    PubMed

    Birketvedt, Grethe S; Geliebter, Allan; Kristiansen, Ingrid; Firgenschau, Yngve; Goll, Rasmus; Florholmen, Jon R

    2012-12-01

    The regulatory peptide ghrelin has been proposed to help mediate both hunger and sleep. The neuroendocrine circadian patterns in the night eating syndrome (NES) have been distinguished by an attenuated nocturnal rise in the plasma concentrations of melatonin and leptin and a greater increase in the concentrations of cortisol. In this study we wanted to test the hypothesis that night eaters have disturbances in the circadian levels of ghrelin, growth hormone (GH) and associated regulatory peptides. In 12 female night eaters (6 normal weight and 6 overweight), and 25 healthy controls (12 normal weight and 13 overweight), blood was sampled over a 24-hour period. Four meals were served from 8 AM to 8 PM, and blood samples were drawn every second hour for determination of plasma ghrelin concentrations and GH by radioimmunoassay (RIA). Analysis of serum GH, IGF-1, IGFBP-3 and prolactin were performed by ELISA. In healthy normal weight subjects there was a slight but non significant nocturnal increase of ghrelin, whereas a more or less flat curve was observed for healthy overweight, NES normal weight and NES overweight patients. The RMANOVA analysis showed a significant independent lowering effect of overweight on the grand mean of ghrelin. No direct effects on NES normal weight and overweight subjects were found, but a near-significant interaction was found between healthy overweight and overweight NES subjects. There were independent significant lowering effects of overweight and NES on the serum GH levels. During the time course no changes in the serum levels of IGF-1 or IGFB-3 were observed. Independent significant lowering effects of overweight and NES on the levels of IGF-1 were detected, whereas a near significant reduction in the global levels of IGFBP-3 was observed in both NES groups. Finally, significant nocturnal changes were observed for serum levels of prolactin in all four subgroups. Grand mean levels tended to be higher in NES subjects whereas the opposite

  13. Vitamin D interferes with transactivation of the growth hormone gene by thyroid hormone and retinoic acid.

    PubMed Central

    Garcia-Villalba, P; Jimenez-Lara, A M; Aranda, A

    1996-01-01

    The thyroid hormone, retinoic acid (RA), and vitamin D regulate gene expression by binding to similar receptors which act as ligand-inducible transcription factors. Incubation of pituitary GH4C1 cells with nanomolar concentrations of vitamin D markedly reduces the response of the rat growth hormone mRNA to thyroid hormone triiodothyronine (T3) and RA. The stimulation of growth hormone gene expression by both ligands is mediated by a common hormone response element (TREGH) present in the 5'-flanking region of the gene, and the inhibition caused by vitamin D is due to transcriptional interference of the vitamin D receptor on this DNA element. No inhibition of the basal promoter activity by the vitamin was observed. The response to T3 and RA of a heterologous promoter containing this element, the palindromic T3- and RA-responsive sequence TREPAL, or a direct repeat of the same motif is also inhibited by vitamin D. In contrast, vitamin D strongly induces the activity of constructs containing a vitamin D response element, and neither T3 nor RA reduces vitamin D-mediated transactivation. Transfection with an expression vector for the retinoid X receptor alpha (RXR alpha) increases transactivation by T3 and RA but does not abolish the inhibition caused by the vitamin. Gel retardation experiments show that the vitamin D receptor (VDR) as a heterodimer with RXR weakly binds to the T3- and RA-responsive elements. Additionally, VDR displaces binding of T3 and RA receptors in a dose-dependent manner. Our data suggest the formation of TR-VDR and RAR-VDR heterodimers with RXR. The fact that the same response element mediates opposite effects of at least four different nuclear receptors provides a greater complexity and flexibility of the transcriptional responses to their ligands. PMID:8524311

  14. History of growth hormone therapy.

    PubMed

    Blizzard, Robert M

    2012-01-01

    The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Serendipity was manifest in 1985 when patients who had received hGH years previously were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. However, the appropriate use and the potential abuse of this hormone are to be dealt with. The

  15. Growth Hormone Deficiency, Brain Development, and Intelligence

    ERIC Educational Resources Information Center

    Meyer-Bahlburg, Heino F. L.; And Others

    1978-01-01

    Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

  16. Human Growth Hormone: The Latest Ergogenic Aid?

    ERIC Educational Resources Information Center

    Cowart, Virginia S.

    1988-01-01

    Believing that synthetic human growth hormone (hGH) will lead to athletic prowess and fortune, some parents and young athletes wish to use the drug to enhance sports performance. Should hGH become widely available, its abuse could present many problems, from potential health risks to the ethics of drug-enhanced athletic performance. (JL)

  17. Growth hormone: health considerations beyond height gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The therapeutic benefit of growth hormone (GH) therapy in improving height in short children is widely recognized; however, GH therapy is associated with other metabolic actions that may be of benefit in these children. Beneficial effects of GH on body composition have been documented in several dif...

  18. Development of growth hormone secretagogues.

    PubMed

    Smith, Roy G

    2005-05-01

    The GH secretagogues (GHS) were developed by reverse pharmacology. The objective was to develop small molecules with pharmacokinetics suitable for once-daily oral administration that would rejuvenate the GH/IGF-I axis. Neither the receptor nor the ligand that controlled pulse amplitude of hormone release was known; therefore, identification of lead structures was based on function. I reasoned that GH pulse amplitude could be increased by four possible mechanisms: 1) increasing GHRH release; 2) amplifying GHRH signaling in somatotrophs of the anterior pituitary gland; 3) reducing somatostatin release; and 4) antagonizing somatostatin receptor signaling. Remarkably, the GHS act through all four mechanisms to reproduce a young adult physiological GH profile in elderly subjects that was accompanied by increased bone mineral density and lean mass, modest improvements in strength, and improved recovery from hip fracture. Furthermore, restoration of thymic function was induced in old mice. The GHS receptor (GHS-R) was subsequently identified by expression cloning and found to be a previously unknown G protein-coupled receptor expressed predominantly in brain, pituitary gland, and pancreas. Reverse pharmacology was completed when the cloned GHS-R was exploited to identify an endogenous agonist (ghrelin) and a partial agonist (adenosine); ghsr-knockout mice studies confirmed that GHS are ghrelin mimetics. PMID:15814848

  19. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    PubMed

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  20. Growth hormone: its physiology and control.

    PubMed

    Scanes, C G; Lauterio, T J

    1984-12-01

    Growth hormone (GH) is a protein hormone produced by the somatotrophs of the anterior pituitary gland of birds and other vertebrates. The secretion of GH in birds is under hypothalamic control; it involves three peptidergic releasing factors: growth hormone-releasing factor (GRF) (stimulatory); thyrotropin-releasing hormone (TRH) (stimulatory); and somatostatin (SRIF) (inhibitory). In addition, there is evidence for effects of biogenic amines (including serotonin and norepinephrine) and prostaglandins at the level of the hypothalamus and possibly also the pituitary gland. In all avian species examined, plasma concentrations of GH are high in young posthatching chicks but low in the adult and embryo. The difference in plasma concentrations of GH between young and adult birds is due to both greater GH secretion and reduced clearance. The lower secretion of GH in adult birds reflects fewer somatotrophs in the pituitary, changes in somatotroph structure, and reduced GH responses to TRH or GRF administration. There is only limited data on the role of GH in birds. GH appears to be required for normal growth; acting at least in part by increasing somatomedin production. However, plasma concentrations of GH do not necessarily correlate with growth rate. For instance, in chicks with reduced growth rate owing to either goitrogen or protein deficiency in the diet, plasma concentrations of GH are elevated. GH also can influence lipid metabolism by increasing lipolysis, decreasing lipogenesis, and stimulating the uptake of glucose by adipose tissue. The physiological significance of these actions is, however, not established. In addition, GH affects the secretion of other hormones, the immune system, and perhaps also the reproductive system. PMID:6151579

  1. Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.

    PubMed

    Lan, Hainan; Zheng, Xin; Khan, Muhammad Akram; Li, Steven

    2015-11-01

    In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors.

  2. Pulse sensitivity of the luteinizing hormone beta promoter is determined by a negative feedback loop Involving early growth response-1 and Ngfi-A binding protein 1 and 2.

    PubMed

    Lawson, Mark A; Tsutsumi, Rie; Zhang, Hao; Talukdar, Indrani; Butler, Brian K; Santos, Sharon J; Mellon, Pamela L; Webster, Nicholas J G

    2007-05-01

    The hypothalamic-pituitary-gonadal endocrine axis regulates reproduction through estrous phase-dependent release of the heterodimeric gonadotropic glycoprotein hormones, LH and FSH, from the gonadotropes of the anterior pituitary. Gonadotropin synthesis and release is dependent upon pulsatile stimulation by the hypothalamic neuropeptide GnRH. Alterations in pulse frequency and amplitude alter the relative levels of gonadotropin synthesis and release. The mechanism of interpretation of GnRH pulse frequency and amplitude by gonadotropes is not understood. We have examined gene expression in LbetaT2 gonadotropes under various pulse regimes in a cell perifusion system by microarray and identified 1127 genes activated by tonic or pulsatile GnRH. Distinct patterns of expression are associated with each pulse frequency, but the greatest changes occur at a 60-min or less interpulse interval. The immediate early gene mRNAs encoding early growth response (Egr)1 and Egr2, which activate the gonadotropin LH beta-subunit gene promoter, are stably induced at high pulse frequency. In contrast, mRNAs for the Egr corepressor genes Ngfi-A binding protein Nab1 and Nab2 are stably induced at low pulse frequency. We show that Ngfi-A binding protein members inhibit Egr-mediated frequency-dependent induction of the LH beta-subunit promoter. This pattern of expression suggests a model of pulse frequency detection that acts by suppressing activation by Egr family members at low frequency and allowing activation at sustained high-frequency pulses.

  3. Prolactin and growth hormone in fish osmoregulation

    USGS Publications Warehouse

    Sakamoto, T.; McCormick, S.D.

    2006-01-01

    Prolactin is an important regulator of multiple biological functions in vertebrates, and has been viewed as essential to ion uptake as well as reduction in ion and water permeability of osmoregulatory surfaces in freshwater and euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin expression in the pituitary and peripheral organs during freshwater adaptation. Growth hormone, a member of the same family of hormones as prolactin, promotes acclimation to seawater in several teleost fish, at least in part through the action of insulin-like growth factor I. In branchial epithelia, development and differentiation of the seawater-type chloride cell (and their underlying biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater-type chloride cell is regulated by prolactin and cortisol. In the epithelia of gastrointestinal tract, prolactin induces cell proliferation during freshwater adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We propose that control of salinity acclimation in teleosts by prolactin and growth hormone primarily involves regulation of cell proliferation, apoptosis, and differentiation (the latter including upregulation of specific ion transporters), and that there is an important interaction of these hormones with corticosteroids. ?? 2005 Elsevier Inc. All rights reserved.

  4. CIDE-A gene expression is decreased in white adipose tissue of growth hormone receptor/binding protein gene disrupted mice and with high-fat feeding of normal mice.

    PubMed

    Kelder, Bruce; Berryman, Darlene E; Clark, Ryan; Li, Aiyun; List, Edward O; Kopchick, John J

    2007-08-01

    Growth hormone's (GH) lipolytic activity in white adipose tissue (WAT) results in decreased body fat in giant GH transgenic mice and increased subcutaneous fat in dwarf growth hormone receptor/binding protein gene-disrupted mice (GHR -/-). We therefore hypothesized that GH action would affect expression of CIDE-A (cell-death-inducing DFF45-like effector-A), a protein found in white adipose tissue (WAT) and involved in lipid metabolism. CIDE-A RNA levels were determined in subcutaneous, retroperitoneal and epididymal adipose tissue isolated from wild-type and GHR -/- mice. The adipose tissue was also analyzed for adipocyte size. We determined that the lack of GH action has depot-specific effects on the levels of CIDE-A RNA and affected adipocyte cell size. CIDE-A expression is significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type mice. A high-fat diet also influenced the level of CIDE-A RNA in mouse adipose tissue. The high-fat diet significantly reduced CIDE-A expression in wild-type subcutaneous fat but did not alter CIDE-A expression in subcutaneous fat of GHR -/- mice. The diet also reduced CIDE-A expression in wild-type retroperitoneal fat but the levels of CIDE-A in epididymal fat were unchanged. In contrast, the high-fat diet reduced CIDE-A expression in both retroperitoneal and epididymal fat of GHR -/- mice. These data demonstrate that CIDE-A levels are reduced in two different mouse models of obesity and this reduction may contribute to altered lipid metabolism. PMID:17544797

  5. Preventing Growth Hormone Abuse: An Emerging Health Concern.

    ERIC Educational Resources Information Center

    White, George L.; And Others

    1989-01-01

    Facts about growth hormone abuse should be incorporated into substance abuse components of health education curriculums. Sources, uses, and dangers associated with human growth hormones are discussed. A sample lesson plan is included. (IAH)

  6. Gravitational effects on plant growth hormone concentration

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.

    1983-01-01

    Dolk's (1936) finding that more growth hormone diffuses from the lower side of a gravity-stimulated plant shoot than from the upper side is presently confirmed by means of both an isotope dilution assay and selected ion monitoring-gas chromatography-mass spectrometry, and it is established that the asymmetrically distributed hormone is indole-3-acetic acid (IAA). This is the first physicochemical demonstration that there is more IAA on the lower sides of a geostimulated plant shoot. It is also found that free IAA primarily occurs in the conductive vascular tissues of the shoot, while IAA esters predominate in the growing cortical cells. A highly sensitive gas chromatographic isotope dilution assay shows that the hormone asymmetry also occurs in the nonvascular tissue.

  7. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    PubMed

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  8. [Growth hormone in children and adolescents: facts and fiction].

    PubMed

    Burckhardt, Marie-Anne; Zumsteg, Urs

    2013-06-19

    Growth Hormone therapy has been used therapeutically for over 50 years. Until recently, growth hormone therapy has been restricted for children and adolescents with proven hypothalamic-pituitary short stature. Today some other causes - but not all - can be treated with growth hormone. To the well-established indications belong apart from proven growth hormone deficiency, children with Turner Syndrome and with Prader Willi Syndrome, children born small for gestational age without catch-up growth and children with chronic kidney disease and with some haematological and oncological diseases. Careful and accurate diagnosis is essential. Growth hormone therapy is rare in everyday practice and requires close cooperation with a pediatric endocrinologist.

  9. Growth hormone therapy in children with chronic renal failure.

    PubMed

    Cayir, Atilla; Kosan, Celalettin

    2015-02-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant human growth hormone is an effective option for patients with inadequate growth rates. PMID:25745347

  10. Effect of growth hormone deficiency on brain structure, motor function and cognition.

    PubMed

    Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and

  11. Ectopic acromegaly due to growth hormone releasing hormone.

    PubMed

    Ghazi, Ali A; Amirbaigloo, Alireza; Dezfooli, Azizollah Abbasi; Saadat, Navid; Ghazi, Siavash; Pourafkari, Marina; Tirgari, Farrokh; Dhall, Dheepti; Bannykh, Serguei; Melmed, Shlomo; Cooper, Odelia

    2013-04-01

    Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly. PMID:22983831

  12. Hepatic receptors for homologous growth hormone in the eel

    SciTech Connect

    Hirano, T. )

    1991-03-01

    The specific binding of 125I-labeled eel growth hormone (eGH) to liver membranes of the eel was examined. The specific binding to the 10,000g pellet was greater than that to the 600g pellet. The specific binding was linear up to about 100 mg fresh tissue, and was saturable with increasing amounts of membrane. The specific binding was pH-, temperature-, and time-dependent, with the optimum pH at 7.4, and greater specific binding was obtained at 15 and 25 degrees than at 35 degrees. Scatchard analysis of liver binding gave an association constant of 1.1 x 10(9) M-1 and a capacity of 105 fmol/mg protein. The receptor preparation was highly specific for GHs. Natural and recombinant eel GHs as well as recombinant salmon GH competed equally with 125I-eGH for the receptor sites of the 10,000g liver membrane. Ovine GH was more potent in displacing the labeled eGH than the homologous eel hormone. Tilapia GH and ovine prolactin (PRL) were needed in greater amounts (40 times) than eGH to displace the labeled eGH. Salmon and tilapia PRLs were still less potent (500 times) than eGH. There was no displacement with eel PRL. No significant change in the specific binding was seen 1 week after hypophysectomy, whereas injection of eGH into the hypophysectomized eel caused a significant reduction after 24 hr. The binding to the membrane fractions from gills, kidney, muscle, intestine, and brain was low and exclusively nonspecific, indicating the presence of specific GH receptors predominantly in the liver.

  13. Internet informs parents about growth hormone

    PubMed Central

    Cousounis, Pamela; Lipman, Terri H.; Ginsburg, Kenneth; Grimberg, Adda

    2013-01-01

    Background Parent knowledge influences decisions regarding medical care for their children. Methods Parents of pediatric primary care patients aged 9-14 years, irrespective of height, participated in open focus groups (OFG). Moderators asked, “How do people find out about growth hormone (GH)?” Because many parents cited the Internet, the top 10 results from the Google searches, growth hormone children and parents of children who take growth hormone, were examined as representative. Three investigators independently performed content analysis, then reached consensus. Results were tabulated via summary statistics. Results Eighteen websites were reviewed, most with the purpose of education (56%) and many funded by commercial sources (44%). GH treatment information varied, with 33% of sites containing content only about U.S Food and Drug Administration-approved indications. Fifty-six percent of sites included information about psychosocial benefits from treatment, 44% acknowledging them as controversial. Although important to OFG participants, risks and costs were each omitted from 39% of websites. Conclusion Parents often turn to the Internet for GH-related information for their children, though its content may be incomplete and/or biased. Clinicians may want to provide parents with tools for critically evaluating Internet-based information, a list of pre-reviewed websites, or their own educational materials. PMID:23942255

  14. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth?

    PubMed Central

    Devesa, Jesús; Almengló, Cristina; Devesa, Pablo

    2016-01-01

    In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown. PMID:27773998

  15. Use of growth hormone in children.

    PubMed

    Hindmarsh, Peter C; Dattani, Mehul T

    2006-05-01

    The introduction of recombinant DNA-derived human growth hormone (rhGH) in the mid-1980s allowed studies to be undertaken in a number of growth disorders other than the classic indication--growth-hormone deficiency (GHD). In patients with GHD, optimizing the dose and frequency of rhGH administration, and early instigation of therapy, has led to near-normalization of final height. The use of rhGH in the treatment of Turner syndrome, Prader-Willi syndrome, intrauterine growth restriction, and chronic renal failure demonstrated the efficacy of therapy, although the increase in final height (5-7 cm) is less than that achieved in GHD. Cost-benefit implications need to be considered in the next phases of evaluating the role of rhGH therapy in these indications. To date, rhGH has only received approval for the management of idiopathic short stature in the US; as with the other wider growth indications, the lack of formal randomized, controlled trials hampers the full evaluation of efficacy, and a cautious approach should, therefore, be adopted for this particular indication. rhGH has a good safety record, although there are current concerns about the possible long-term increased risk of colonic and lymphatic malignancy, which will require monitoring through national cancer registries. PMID:16932297

  16. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  17. Role of abnormal anterior pituitary hormones-growth hormone and prolactin in active systemic lupus erythematosus

    PubMed Central

    Zhu, Xiaohua; Xu, Jinhua; Li, Shujuan; Huang, Wen; Li, Feng

    2015-01-01

    Background: The role of anterior pituitary hormones in systemic lupus erythematosus (SLE) remains controversial. Aims and Objectives: We determined the expression levels of human growth hormone (GH), prolactin (PRL), and their receptors in subjects presenting with SLE, and modulation of disease severity. Materials and methods: Forty-seven subjects and ten healthy controls were assessed for possible association between SLE disease activity and levels of serum PRL, GH and thyrotropin-releasing hormone (TRH). In peripheral blood mononuclear cells (PBMC), specific binding and mRNA expression of receptors for GH (GHR), and PRL (PRLR) were determined by receptor-ligand binding assay (RLBA) and RT-PCR. PBMC of recruited subjects were treated with hPRL and rhGH to assess IgG production and antibodies against dsDNA. Results: In active SLE subjects we found elevated PRL and GH levels. Study subject PBMCs displayed augmented GHR and PRLR protein and mRNA expression. Study subjects also showed a positive correlation in serum PRL levels and specific antibodies against dsDNA, SLE disease activity index (SLEDAI), and proteinuria. However, a negative correlation was found between serum PRL levels and complement component C3. We found a positive correlation between specific binding rates of PRLR and GHR and both SLE activity and dsDNA antibody titers. Enhanced IgG and anti-dsDNA secretion was observed in cultured PBMC stimulated by PRL or GH with/without PHA, PWM, IL-2 or IL-10. In active SLE, a close association was found between augmented PRL and GH levels, expression and specific binding activities of PRLR and GHR, and changes in the specific titer of anti-dsDNA. Conclusion: Anterior pituitary hormones play an important role in the pathogenesis of SLE. High levels of growth hormone (GH) and prolactin (PRL) play a role in pathogenesis of SLE, which is correlated with SLE disease activity and antibodies against dsDNA. The mechanism of GH and PRL in SLE was complicated and should

  18. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    PubMed

    Harvey, S; Gineste, C; Gaylinn, B D

    2014-08-01

    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.

  19. The pituitary growth hormone cell in space

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.; Grindeland, R.

    1989-01-01

    Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

  20. Pathology of excessive production of growth hormone.

    PubMed

    Scheithauer, B W; Kovacs, K; Randall, R V; Horvath, E; Laws, E R

    1986-08-01

    Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of

  1. Infantile Growth Hormone Deficiency and X- Linked Adrenal Hypoplasia Congenita

    PubMed Central

    Chung, Stephanie T.; Chi, Carolyn H.; Haymond, Morey W.; Jeha, George S.

    2015-01-01

    Context X-linked adrenal hypoplasia congenita (AHC) is a rare but important cause of primary adrenal insufficiency and can be associated with significant morbidity and mortality. AHC is caused by mutations within the NROB1 gene that codes for the DAX-1 protein, an orphan nuclear receptor essential for the development of the hypothalamic-pituitary-adrenal axis. Affected individuals typically present in early infancy with adrenal insufficiency and growth is usually normal once medical therapy is instituted. Here we report the first case of growth hormone deficiency in an infant with AHC and a novel NROB1 missense mutation. Case A two-week old infant presented with salt-losing adrenal crises and a normal newborn screen. Tests of adrenal function confirmed adrenal hypoplasia congenita and molecular evaluation revealed a novel missense NROB1 mutation. Replacement steroid therapy was promptly initiated, but he subsequently developed growth failure despite optimal nutritional and medical steroid therapy. Further biochemical analyses confirmed isolated idiopathic growth hormone deficiency. Conclusions Growth failure in adequately treated infants with adrenal hypoplasia congenita is rare and the role of DAX-1 in the development of pituitary somatotropes is not known. There is variable genotype-phenotype correlation in X-linked adrenal hypoplasia congenita but novel NROB1 missense mutations could offer insight into the function of the various DAX-1 ligand-binding domains. PMID:27110597

  2. Relationship between urinary and serum growth hormone and pubertal status.

    PubMed Central

    Crowne, E C; Wallace, W H; Shalet, S M; Addison, G M; Price, D A

    1992-01-01

    Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty. PMID:1739346

  3. Sex steroids, growth hormone, leptin and the pubertal growth spurt.

    PubMed

    Rogol, Alan D

    2010-01-01

    A normal rate for the linear growth of a child or adolescent is a strong statement for the good general health of that child. Normal growth during childhood is primarily dependent on adequate nutrition, an adequate psychosocial environment, the absence of disease and adequate amounts thyroid hormone and growth hormone (and its downstream product, IGF-1). At adolescence there is the reawakening of the hypothalamic-pituitary-gonadal axis and its interaction with the GH/IGF-1 axis to subserve the pubertal growth spurt. The fat tissue-derived hormone, leptin and its receptor are likely involved in at least two aspects of pubertal development - sexual development itself and the alterations in body composition including the regional distribution of fat and bone mineralization. During the prepubertal years the male female differences in body composition are quite modest, but change remarkably during pubertal development with boys showing a relative decrement in fat percentage and girls a marked increase in concert with rising levels of circulating leptin. The boys show a much greater increase in lean body tissue and the relative proportions of water, muscle and bone. These may be observed as the differential growth of the shoulders and hips. The net effect of these pubertal changes is that the young adult woman has approximately 25% body fat in the 'gynoid' distribution while the male has much more muscle, especially in the shoulders and upper body but only approximately 13% body fat.

  4. Growth hormone secretagogues: prospects and potential pitfalls.

    PubMed

    Smith, Roy G; Sun, Yuxiang; Betancourt, Lorena; Asnicar, Mark

    2004-09-01

    The growth hormone secretagogues (GHSs) are the first well-characterised agents that rejuvenate the growth hormone (GH)/insulin-like growth factor (IGF-1) axis. This property was discovered during investigations of the underlying causative mechanisms of age-related endocrine changes. Chronic administration of the long acting GHS, MK-0677, reverses the age-related decline in pulse-amplitude of GH secretion and restores IGF-1 levels producing profiles typical of young adults. This restoration is accompanied by improvements in body composition in frail elderly subjects. When given acutely, the GHSs also increase appetite. Following cloning and characterisation of the GHS-receptor (GHS-R) an endogenous ligand, ghrelin, was isolated and identified. Ghrelin shares the GH releasing and orexigenic properties of the GHSs. Studies using Ghsr-null mice confirmed that the GHS-R was the ghrelin-receptor; hence, the GHSs should be considered to be 'ghrelin mimetics.' Ghrelin levels are reported to decline during ageing, therefore long-acting GHSs are ideal candidates for ghrelin replacement therapy. PMID:15261841

  5. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    SciTech Connect

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  6. Random Secretion of Growth Hormone in Humans

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  7. Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site

    PubMed Central

    Naranda, Tatjana; Wong, Kenneth; Kaufman, R. Ilene; Goldstein, Avram; Olsson, Lennart

    1999-01-01

    Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin. PMID:10377456

  8. Gravitational effects on plant growth hormone concentration

    NASA Astrophysics Data System (ADS)

    Bandurski, Robert S.; Schulze, Aga

    Numerous studies, particularly those of H. Dolk in the 1930's, established by means of bio-assay, that more growth hormone diffused from the lower, than from the upper side of a gravity-stimulated plant shoot. Now, using an isotope dilution assay, with 4,5,6,7 tetradeutero indole-3-acetic acid as internal standard, and selected ion monitoring-gas chromatography-mass spectrometry as the method of determination, we have confirmed Dolk's finding and established that the asymmetrically distributed hormone is, in fact, indole-3-acetic acid (IAA). This is the first physico-chemical demonstration that there is more free IAA on the lower sides of a geo-stimulated plant shoot. We have also shown that free IAA occurs primarily in the conductive vascular tissues of the shoot, whereas IAA esters predominate in the growing cortical cells. Now, using an especially sensitive gas chromatographic isotope dilution assay we have found that the hormone asymmetry also occurs in the non-vascular tissue. Currently, efforts are directed to developing isotope dilution assays, with picogram sensitivity, to determine how this asymmetry of IAA distribution is attained so as to better understand how the plant perceives the geo-stimulus.

  9. Thyroid hormones and growth in health and disease.

    PubMed

    Tarım, Ömer

    2011-01-01

    Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children.

  10. Potential role of human growth hormone in melanoma growth promotion.

    PubMed

    Handler, Marc Z; Ross, Andrew L; Shiman, Michael I; Elgart, George W; Grichnik, James M

    2012-10-01

    BACKGROUND Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation. OBSERVATION A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior. CONCLUSIONS Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance. PMID:23069955

  11. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    SciTech Connect

    Kikuchi, M.; Ishii, S. )

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  12. Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

    PubMed

    Lindsey, Richard C; Mohan, Subburaman

    2016-09-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis.

  13. [Localized lipohypertrophy during growth hormone therapy].

    PubMed

    Mersebach, Henriette; Feldt-Rasmussen, Ulla F

    2002-04-01

    Accumulation of subcutaneous fat is described in a 51-year-old woman with panhypopituitarism treated on all insufficient pituitary axes, including growth hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as biochemical marker of the GH effect was compromised. Peripheral levels of GH and IGF-I in tissues may have reached supra physiological levels and induced localised lipohypertrophy. Adjustment of GH treatment should not rest in all cases on IGF-I alone, but also depend on the clinical effect. Adjustment should follow suspected adverse events, such as lipohypertrophy, which is, however, an unusual complication of GH therapy.

  14. Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

    ERIC Educational Resources Information Center

    Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

    2012-01-01

    The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

  15. Detecting growth hormone misuse in athletes.

    PubMed

    Holt, Richard I G

    2013-10-01

    Athletes have been misusing growth hormone (GH) for its anabolic and metabolic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Although there is an ongoing debate about whether GH is performance enhancing, recent studies suggest that GH improves strength and sprint capacity, particularly when combined with anabolic steroids. The detection of GH misuse is challenging because it is an endogenous hormone. Two approaches have been developed to detect GH misuse; the first is based on the measurement of pituitary GH isoforms and the ratio of 22-kDa isoform to total GH. The second is based on the measurement of insulin like growth factor-I (IGF-I) and N-terminal propeptide of type III procollagen (P-III-NP) which increase in a dose-dependent manner in response to GH administration. Both methodologies have been approved by the World Anti-Doping Agency (WADA) and have led to the detection of a number of athletes misusing GH.

  16. Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth, and development.

    PubMed

    Mahajan, Muktar A; Samuels, Herbert H

    2005-06-01

    Nuclear hormone receptor coregulator (NRC) (also referred to as activating signal cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator activating receptor-interacting protein, and 250-kDa receptor associated protein) belongs to a growing class of nuclear cofactors widely known as coregulators or coactivators that are necessary for transcriptional activation of target genes. The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal activation domain (AD1) and a second more centrally located activation domain (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif (LxxLL-2) located in the C-terminal region of NRC is more restricted in its nuclear hormone receptor specificity. The intrinsic activation potential of NRC is regulated by a C-terminal serine, threonine, leucine-regulatory domain. The potential role of NRC as a cointegrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known transcriptional regulators including CBP/p300. Recent studies in mice indicate that deletion of both NRC alleles leads to embryonic lethality resulting from general growth retardation coupled with developmental defects in the heart, liver, brain, and placenta. NRC(-/-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6 NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing.

  17. Parathyroid hormone linked to a collagen binding domain (PTH-CBD) promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner

    PubMed Central

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and can influence treatment decisions. While there is currently no therapy, PTH-CBD, a fusion protein of parathyroid hormone and collagen binding domain, has shown promise in animal models. Objective To determine if there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. Methods C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320 and 1000 mcg/kg subcutaneous injection); treated on day 9 with vehicle or cyclophosphamide (150 mg/kg i.p.). Mice were photographed every 3–4 days and sacrificed on day 63 for histological analysis. Photographs were quantified by grey scale analysis to assess hair content. Results Mice not receiving chemotherapy showed regrowth of hair 2 weeks following waxing, and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histology revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by grey scale analysis, p<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to mice which did not receive chemotherapy. Conclusions Single dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding recovery from chemotherapy-induced alopecia. PMID:24710191

  18. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    SciTech Connect

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-08-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation.

  19. Role of sex-hormone-binding globulin and free sex steroid hormones in hyperandrogenic anovulation.

    PubMed

    Ohsawa, M; Asai, M; Masahashi, T; Narita, O; Tomoda, Y; Matsui, N

    1986-11-01

    To clarify the mechanism of hyperandrogenic anovulation, the binding capacity of sex-hormone-binding globulin (SHBG-BC), the levels of free steroid hormones, and the levels of basal serum testosterone (T), estradiol (E2), estrone (E1) and gonadotropins were determined in 42 hyperandrogenic anovulatory women. The mean levels of basal T (0.74 +/- 0.04 ng/ml, p less than 0.001), free T (3.07 +/- 0.51 ng/dl, p less than 0.01) and free E2 (2.26 +/- 0.27 pg/ml, p less than 0.05), basal luteinizing hormone (LH) (33.4 +/- 2.7 mIU/ml, p less than 0.001), responsiveness of LH (180.7 +/- 21.5 mIU/ml, p less than 0.001) after luteinizing hormone releasing hormone (LHRH) administration, and the basal LH/basal follicle stimulating hormone (FSH) ratio (3.42 +/- 0.25, p less than 0.001) in the patients were significantly higher, the SHBG-BC level (1.76 +/- 0.33 micrograms DHT bound/dl, p less than 0.05) significantly reduced, and basal levels of E2 (38.0 +/- 3.2 pg/ml) and E1 (110 +/- 13 pg/ml) unchanged compared to the controls. These findings suggest that increased T in hyperandrogenic anovulatory women results in decreased SHBG-BC and increased free T and E2 which might be the cause of inappropriate gonadotropin secretion followed by chronic anovulation. PMID:2947958

  20. Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

    SciTech Connect

    Demay, M.; Mitchell, J.; Goltzman, D.

    1985-11-01

    The authors compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding.

  1. The influence of growth hormone on bone and adipose programming.

    PubMed

    Oberbauer, Anita M

    2014-01-01

    In utero growth hormone exposure is associated with distinct immediate growth responses and long term impacts on adult physiological parameters that include obesity, insulin resistance, and bone function. Growth hormone accelerates cellular proliferation in many tissues but is exemplified by increases in the number of cells within the cartilaginous growth plate of bone. In some cases growth hormone also potentiates differentiation as seen in the differentiation of adipocytes that rapidly fill upon withdrawal of growth hormone. Growth hormone provokes these changes either by direct action or through intermediaries such as insulin-like growth factor-I and other downstream effector molecules. The specific mechanism used by growth hormone in programming tissues is not yet fully characterized and likely represents a multipronged approach involving DNA modification, altered adult hormonal milieu, and the development of an augmented stem cell pool capable of future engagement as is seen in adipose accrual. This review summarizes findings of growth hormone's influence on in utero and neonatal cellular and metabolic profiles related to bone and adipose tissue.

  2. Growth hormone modulation of arginine-induced glucagon release: studies of isolated growth hormone deficiency and acromegaly.

    PubMed

    Seino, Y; Taminato, T; Goto, Y; Inoue, Y; Kadowaki, S; Hattori, M; Mori, K; Kato, Y; Matsukura, S; Imura, H

    1978-12-01

    Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.

  3. Growth hormone deficiency in treated acromegaly.

    PubMed

    Mazziotti, Gherardo; Marzullo, Paolo; Doga, Mauro; Aimaretti, Gianluca; Giustina, Andrea

    2015-01-01

    Growth hormone deficiency (GHD) of the adult is characterized by reduced quality of life (QoL) and physical fitness, skeletal fragility, and increased weight and cardiovascular risk. Hypopituitarism may develop in patients after definitive treatment of acromegaly, but an exact prevalence of GHD in this population is still uncertain owing to limited awareness and the scarce and conflicting data available on this topic. Because acromegaly and GHD may yield adverse consequences on similar target systems, the final outcomes of some complications of acromegaly may be further affected by the occurrence of GHD. However, it is still largely unknown whether patients with post-acromegaly GHD may benefit from GH replacement. We review the diagnostic, clinical, and therapeutic aspects of GHD in adult patients treated for acromegaly.

  4. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer

    SciTech Connect

    Brown, Richard J.; Adams, Julian J.; Pelekanos, Rebecca A.; Wan, Yu; McKinstry, William J.; Palethorpe, Kathryn; Seeber, Ruth M.; Monks, Thea A.; Eidne, Karin A.; Parker, Michael W.; Waters, Michael J.

    2010-07-13

    Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

  5. Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

    PubMed Central

    Ayers, Stephen; Switnicki, Michal Piotr; Angajala, Anusha; Lammel, Jan; Arumanayagam, Anithachristy S.; Webb, Paul

    2014-01-01

    Thyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities of TR genomic distribution and links between TRβ binding events and gene regulation are not fully appreciated. Here, we employ a BioChIP approach to capture TR genome-wide binding events in a liver cell line (HepG2). Like other NRs, TRβ appears widely distributed throughout the genome. Nevertheless, there is striking enrichment of TRβ binding sites immediately 5′ and 3′ of transcribed genes and TRβ can be detected near 50% of T3 induced genes. In contrast, no significant enrichment of TRβ is seen at negatively regulated genes or genes that respond to unliganded TRs in this system. Canonical TRE half-sites are present in more than 90% of TRβ peaks and classical TREs are also greatly enriched, but individual TRE organization appears highly variable with diverse half-site orientation and spacing. There is also significant enrichment of binding sites for TR associated transcription factors, including AP-1 and CTCF, near TR peaks. We conclude that T3-dependent gene induction commonly involves proximal TRβ binding events but that far-distant binding events are needed for T3 induction of some genes and that distinct, indirect, mechanisms are often at play in negative regulation and unliganded TR actions. Better understanding of genomic context of TR binding sites will help us determine why TR regulates genes in different ways and determine possibilities for selective modulation of TR action. PMID:24558356

  6. Sex hormone binding globulin and corticosteroid binding globulin as major effectors of steroid action.

    PubMed

    Caldwell, Jack D; Jirikowski, Gustav F

    2014-03-01

    Contrary to the long-held postulate of steroid-hormone binding globulin action, these protein carriers of steroids are major players in steroid actions in the body. This manuscript will focus on our work with sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) and demonstrate how they are actively involved in the uptake, intracellular transport, and possibly release of steroids from cells. This manuscript will also discuss our own findings that the steroid estradiol is taken up into the cell, as demonstrated by uptake of fluorescence labeled estradiol into Chinese hamster ovary (CHO) cells, and into the cytoplasm where it may have multiple actions that do not seem to involve the cell nucleus. This manuscript will focus mainly on events in two compartments of the cell, the plasma membrane and the cytoplasm.

  7. Sex Hormone-Binding Globulin in Children and Adolescents

    PubMed Central

    Aydın, Banu; Winters, Stephen J.

    2016-01-01

    Sex hormone-binding globulin (SHBG) is a circulating glycoprotein that transports testosterone and other steroids in the blood. Interest in SHBG has escalated in recent years because of its inverse association with obesity and insulin resistance, and because many studies have linked lower circulating levels of SHBG to metabolic syndrome, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary syndrome, and early puberty. The purpose of this review is to summarize molecular, clinical, endocrine, and epidemiological findings to illustrate how measurement of plasma SHBG may be useful in clinical medicine in children. PMID:26761949

  8. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

    PubMed

    Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men. PMID:26778261

  9. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

    PubMed

    Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

  10. Effect of growth hormone on cardiac function.

    PubMed

    Lombardi, G; Colao, A; Ferone, D; Marzullo, P; Orio, F; Longobardi, S; Merola, B

    1997-01-01

    At present, there is a growing body of evidence implicating growth hormone (GH) and/or insulin-like growth factor-I (IGF-I) in the intricate cascade of events connected with the regulation of heart development and hypertrophy. In addition, advanced clinical manifestations of abnormal GH levels almost always include impaired cardiac function, which may reduce life expectancy. This finding is related both to a primary impairment of heart structure and function and to metabolic changes such as hyperlipidaemia, increased body fat and premature atherosclerosis. Acromegalic cardiomyopathy is better correlated with disease duration than with GH or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often result in increased right and left ventricular mass concentric hypertrophy. Conversely, patients with childhood or adult-onset GH deficiency (GHD) have a reduced left ventricular mass (LVM) and ejection fraction (EF) and the indices of left ventricular systolic function remained markedly depressed during exercise. Cardiac function is reported to improve during octreotide and GH replacement treatment in acromegaly and GHD, respectively. The evidence that GH can increase cardiac mass suggests its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of recombinant GH (rGH) was demonstrated to increase myocardial mass and reduce the size of the left ventricular chamber, resulting in improved haemodynamics, myocardial energy metabolism and clinical status. PMID:9350445

  11. Growth hormone and aging: A challenging controversy

    PubMed Central

    Bartke, Andrzej

    2008-01-01

    Although advanced age or symptoms of aging are not among approved indications for growth hormone (GH) therapy, recombinant human GH (rhGH) and various GH-related products are aggressively promoted as anti-aging therapies. Well-controlled studies of the effects of rhGH treatment in endocrinologically normal elderly subjects report some improvements in body composition and a number of undesirable side effects in sharp contrast to major benefits of GH therapy in patients with GH deficiency. Controversies surrounding the potential utility of GH in treatment of a geriatric patient are fueled by increasing evidence linking GH and cancer and by remarkably increased lifespan of GH-resistant and GH-deficient mice. Conservation of cellular signaling mechanisms that influence aging in organisms ranging from worms to mammals suggests that at least some of the results obtained in mutant mice are applicable to the human. We suggest that the normal, physiological functions of GH in promoting growth, sexual maturation and fecundity involve significant costs in terms of aging and life expectancy. Natural decline in GH levels during aging likely contributes to concomitant alterations in body composition and vigor but also may be offering important protection from cancer and other age-associated diseases. PMID:19281058

  12. Extrapituitary growth hormone synthesis in humans.

    PubMed

    Pérez-Ibave, Diana Cristina; Rodríguez-Sánchez, Iram Pablo; Garza-Rodríguez, María de Lourdes; Barrera-Saldaña, Hugo Alberto

    2014-01-01

    The gene for pituitary growth hormone (GH-N) in man belongs to a multigene locus located at chromosome 17q24.2, which also harbors four additional genes: one for a placental variant of GH-N (named GH-V) and three of chorionic somatommamotropin (CSH) type. Their tandem arrangement from 5' to 3' is: GH-N, CSH-L, CSH-1, GH-V and CSH-2. GH-N is mainly expressed in the pituitary from birth throughout life, while the remaining genes are expressed in the placenta of pregnant women. Pituitary somatotrophs secrete GH into the bloodstream to act at receptor sites in most tissues. GH participates in the regulation of several complex physiological processes, including growth and metabolism. Recently, the presence of GH has been described in several extrapituitary sites, such as neural, ocular, reproductive, immune, cardiovascular, muscular, dermal and skeletal tissues. It has been proposed that GH has an autocrine action in these tissues. While the body of evidence for its presence is constantly growing, research of its possible function and implications lag behind. In this review we highlight the evidence of extrapituitary synthesis of GH in humans.

  13. Long-Acting Growth Hormone: An Update.

    PubMed

    Saenger, Paul H; Mejia-Corletto, Jorge

    2016-01-01

    After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.

  14. Studies on the nature of plasma growth hormone

    NASA Technical Reports Server (NTRS)

    Ellis, S.; Grindeland, R. E.; Reilly, T. J.; Yang, S. H.

    1976-01-01

    The paper presents further evidence for the existence of two discrete forms of growth hormone in human plasma, one which is detectable by both radioimmunoassay and bioassay and is immunoreactive, and the other, termed 'bioactive', which is detected by tibial bioassay but shows little reactivity with currently available antisera to pituitary growth hormone. The same division of immunoactive and bioactive growth hormone occurs in rats, though with less disparity. Tests on rats indicated that the bioactive hormone is preferentially released into jugular vein plasma and that plasma concentrations of the bioactive hormone can be enhanced by insulin administration. The bioactive hormone was detectable by tibial assays in Cohn fractions IV, IV-1, and IV-4, and could be concentrated about 40-fold by fractionation with (NaPO3)6 and (NH4)2SO4.

  15. Synthesis and binding affinity of an iodinated juvenile hormone

    SciTech Connect

    Prestwich, G.D.; Eng, W.S.; Robles, S.; Vogt, R.G.; Wisniewski, J.R.; Wawrzenczyk, C.

    1988-01-25

    The synthesis of the first iodinated juvenile hormone (JH) in enantiomerically enriched form is reported. This chiral compound, 12-iodo-JH I, has an iodine atom replacing a methyl group of the natural insect juvenile hormone, JH I, which is important in regulating morphogenesis and reproduction in the Lepidoptera. The unlabeled compound shows approximately 10% of the relative binding affinity for the larval hemolymph JH binding protein (JHBP) of Manduca sexta, which specifically binds natural /sup 3/H-10R,11S-JH I (labeled at 58 Ci/mmol) with a KD of 8 X 10(-8) M. It is also approximately one-tenth as biologically active as JH I in the black Manduca and epidermal commitment assays. The 12-hydroxy and 12-oxo compounds are poor competitors and are also biologically inactive. The radioiodinated (/sup 125/I)12-iodo-JH I can be prepared in low yield at greater than 2500 Ci/mmol by nucleophilic displacement using no-carrier-added /sup 125/I-labeled sodium iodide in acetone; however, synthesis using sodium iodide carrier to give the approximately 50 Ci/mmol radioiodinated ligand proceeds in higher radiochemical yield with fewer by-products and provides a radioligand which is more readily handled in binding assays. The KD of (/sup 125/I)12-iodo-JH I was determined for hemolymph JHBP of three insects: M. sexta, 795 nM; Galleria mellonella, 47 nM; Locusta migratoria, 77 nM. The selectivity of 12-iodo-JH I for the 32-kDa JHBP of M. sexta was demonstrated by direct autoradiography of a native polyacrylamide gel electrophoresis gel of larval hemolymph incubated with the radioiodinated ligand. Thus, the in vitro and in vivo activity of 12-iodo-JH I indicate that it can serve as an important new gamma-emitting probe in the search for JH receptor proteins in target tissues.

  16. Metabolism of growth hormone releasing peptides.

    PubMed

    Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2012-12-01

    New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two

  17. PLGA microsphere-mediated growth hormone release hormone expression induces intergenerational growth.

    PubMed

    Ren, Xiao-Hui; Zhang, Yong-Liang; Luo, Hu-Ying; Li, Hong-Yi; Liu, Song-Cai; Zhang, Ming-Jun; Ouyang, Song-Ying; Xi, Qian-Yun; Jiang, Qing-Yan

    2009-01-01

    To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects of polylactic-co-glycolic acid (PLGA) encapsulated plasmid-mediated GHRH supplements, pCMV-Rep-GHRH microspheres were injected into pregnant mice. Growth and expression of GHRH were measured in the offspring. RT-PCR and immunohistochemistry reveal GHRH expression 3-21 days post-injection. The proportion of GH-positive cells in the GHRH treated offspring was 48.2% higher than in the control group (P < 0.01). The GHRH treated offspring were 6.15% (P < 0.05) larger than the control offspring. At day 49 post-injection, IGF-I serum levels were significantly higher in the treatment group than in the control group. This study confirms that intramuscular expression of GHRH mediated by PLGA microspheres significantly enhances intergenerational growth.

  18. JAK2 activation by growth hormone and other cytokines

    PubMed Central

    Waters, Michael J.; Brooks, Andrew J.

    2015-01-01

    Growth hormone (GH) and structurally related cytokines regulate a great number of physiological and pathological processes. They do this by coupling their single transmembrane domain (TMD) receptors to cytoplasmic tyrosine kinases, either as homodimers or heterodimers. Recent studies have revealed that many of these receptors exist as constitutive dimers rather than being dimerized as a consequence of ligand binding, which has necessitated a new paradigm for describing their activation process. In the present study, we describe a model for activation of the tyrosine kinase Janus kinase 2 (JAK2) by the GH receptor homodimer based on biochemical data and molecular dynamics simulations. Binding of the bivalent ligand reorientates and rotates the receptor subunits, resulting in a transition from a form with parallel TMDs to one where the TMDs separate at the point of entry into the cytoplasm. This movement slides the pseudokinase inhibitory domain of one JAK kinase away from the kinase domain of the other JAK within the receptor dimer–JAK complex, allowing the two kinase domains to interact and trans-activate. This results in phosphorylation and activation of STATs and other signalling pathways linked to this receptor which then regulate postnatal growth, metabolism and stem cell activation. We believe that this model will apply to most if not all members of the class I cytokine receptor family, and will be useful in the design of small antagonists and agonists of therapeutic value. PMID:25656053

  19. Growth hormone-releasing factor (GRF) induced growth hormone advances puberty in female buffaloes.

    PubMed

    Haldar, A; Prakash, B S

    2006-05-01

    Exogenous bovine growth hormone-releasing factor (bGRF) at the dose rate of 10 microg/100 kg body weight was administered intravenously (i.v.) to six Murrah buffalo heifers as treatment group, while another six buffalo heifers served as control group which received the vehicle (0.9% NaCl solution) at an interval of 15 days for a period of 9 months to study the effect of bGRF on puberty onset associated with temporal hormonal changes in peri-pubertal buffalo heifers. Blood samples were collected at 3-day interval from all the animals during the experimental period and plasma harvested was assayed for growth hormonal (GH), luteinizing hormone (LH) and progesterone. The day that plasma progesterone was greater than 1.0 ng/ml for three consecutive sampling days was defined as the day of puberty. Exogenous bGRF administration increased (P = 0.02) plasma GH concentration in treatment group over control group during the treatment of bGRF as well as during the peri-pubertal period. Plasma progesterone concentrations increased transiently earlier (P = 0.05) by 58.5 days in bGRF-treated buffaloes than that in the control group. However, plasma LH concentrations were unaffected by the treatment of bGRF (P = 0.48). Both plasma GH and LH in the buffalo heifers increased (P < 0.01) over time preceding puberty and the higher hormonal concentrations were maintained during the onset of puberty, and thereafter, the concentrations of both the hormones declined (P < 0.05) after puberty. GH and LH were positively correlated both before puberty (r = +0.59 and +0.63; P < 0.05 for control and treatment group, respectively) and after puberty (r = +0.42 and +0.46; P < 0.05 for control and treatment group, respectively) indicating the interaction and/or close relationship of GH and LH in the mechanism of puberty in buffalo species. PMID:16011881

  20. Outcome of growth hormone therapy in children with growth hormone deficiency showing an inadequate response to growth hormone-releasing hormone.

    PubMed

    Saenger, P; Pescovitz, O H; Bercu, B B; Murray, F T; Landy, H; Brentzel, J; O'Dea, L; Hanson, B; Howard, C; Reiter, E O

    2001-06-01

    Saizen (recombinant growth hormone [GH]), 0.2 mg/(kg x wk), was given in an open-label fashion for an average of 51 mo to 27 children with presumed idiopathic GH deficiency who had withdrawn from a trial of Geref (recombinant GH-releasing hormone [GHRH] 1-29) because of inadequate height velocity (HV) (25 children), the onset of puberty (1 child), or injection site reactions (1 child). Measurements were made every 3-12 mo of a number of auxologic variables, including HV, height standard deviation score, and bone age. The children in the study showed excellent responses to Saizen. Moreover, first-year growth during Saizen therapy was inversely correlated with the GH response to provocative GHRH testing carried out 6 and 12 mo after the initiation of Geref treatment. These findings indicate that GH is effective in accelerating growth in GH-deficient children who do not show or maintain a satisfactory response to treatment with GHRH. In addition, they suggest that the initial response to GH therapy used in this way can be predicted by means of provoc-ative testing.

  1. Associations of Testosterone and Sex Hormone Binding Globulin with Adipose Tissue Hormones in Midlife Women

    PubMed Central

    Wildman, Rachel P.; Wang, Dan; Fernandez, Ivonne; Mancuso, Peter; Santoro, Nanette; Scherer, Philipp E.; Sowers, MaryFran R.

    2014-01-01

    Objective Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. Design and Methods Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow-up visit of the multiethnic Study of Women’s Health Across the Nation. Results T was weakly negatively associated with both HMW adiponectin and sOB-R (r = −0.12 and r = −0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = −0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. Conclusions These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women. PMID:23592672

  2. Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

    PubMed

    Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

    2005-04-01

    Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed. PMID:15851094

  3. Secretory pattern of canine growth hormone

    SciTech Connect

    French, M.B.; Vaitkus, P.; Cukerman, E.; Sirek, A.; Sirek, O.V.

    1987-02-01

    The aim of this paper was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of approx. 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h.

  4. Justified and unjustified use of growth hormone

    PubMed Central

    van der Lely, A J

    2004-01-01

    Growth hormone (GH) replacement therapy for children and adults with proven GH deficiency due to a pituitary disorder has become an accepted therapy with proven efficacy. GH is increasingly suggested, however, as a potential treatment for frailty, osteoporosis, morbid obesity, cardiac failure, and various catabolic conditions. However, the available placebo controlled studies have not reported many significant beneficial effects, and it might even be dangerous to use excessive GH dosages in conditions in which the body has just decided to decrease GH actions. GH can indeed induce changes in body composition that are considered to be advantageous to GH deficient and non-GH deficient subjects. In contrast to GH replacement therapy in GH deficient subjects, however, excessive GH action due to GH misuse seems to be ineffective in improving muscle power. Moreover, there are no available study data to indicate that the use of GH for non-GH deficient subjects should be advocated, especially as animal data suggest that lower GH levels are positively correlated with longevity. PMID:15466991

  5. Effects of growth hormone in osteoporosis.

    PubMed

    Aloia, J F; Zanzi, I; Ellis, K; Jowsey, J; Roginsky, M; Wallach, S; Cohn, S H

    1976-11-01

    The effect of chronic administration of growth hormone (GH) to osteoporotic patients was studied using the techniques of total body neutron activation analysis, whole body counting, calcium tracer kinetics, photon absorptiometry, quantitative microradiography, and urinary hydroxyproline. Two dosage schedules were utilized for six months each: 2 units daily and 0.2 w3/4 units of GH daily (where W represents body weight expressed in kg). The lower dosage (2 units) did not produce any appreciable change in the indices studied. Following the higher dose, no evidence of any anabolic effect was apparent in most patients (i.e., no increase in total body levels of Ca, Na, K, P, or Cl). Increases were noted in the urinary calcium excretion rate and in the urinary hydroxyproline excretion. Bone mineral content decreased. The bone biopsies displayed an increase in bone formation and resorption surfaces in response to treatment, but these changes were not statistically significant. It may be concluded that under the conditions of this study, GH administration did not result in an increment in skeletal mass. Several side effects that are characteristic of acromegaly were observed, including hyperglycemia, hypertension, arthralgia, and the carpal tunnel syndrome. Because of the lack of demonstrated benefit and the associated complications of therapy, GH administration does not appear to be of value in the treatment of osteoporosis.

  6. The physiology of growth hormone and sport.

    PubMed

    Widdowson, W Matthew; Healy, Marie-Louise; Sönksen, Peter H; Gibney, James

    2009-08-01

    The growth hormone (GH)/ insulin-like growth factor-I (IGF-I) axis exerts short-and long-term metabolic effects that are potentially important during exercise. Exercise is a potent stimulus to GH release and there is some evidence that the acute increase in GH is important in regulating substrate metabolism post-exercise. Regular exercise also increases 24-hour GH secretion rates, which potentially contributes to the physiologic changes induced by training. The effects of GH replacement in GH-deficient adults provide a useful model with which to study the effects of the more long-term effects of the GH/ IGF-I axis. There is convincing evidence that GH replacement increases exercise capacity. Measures of exercise performance including maximal oxygen uptake (VO2max) and ventilatory threshold (VeT) are impaired in GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition and improved thermoregulation. Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a "window" exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.

  7. Detecting growth hormone abuse in athletes.

    PubMed

    Holt, Richard I G

    2011-08-01

    It is believed that athletes have been abusing growth hormone (GH) for its anabolic and lipolytic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. There is an on-going debate about whether GH is performance enhancing. Although many of the early studies were negative, more recent studies suggest that GH improves strength and sprint capacity, particularly when it is combined with anabolic steroids. Although use of GH is banned by the World Anti-Doping Agency (WADA), its detection remains challenging. Two approaches have been developed to detect GH abuse. The first is based on measurement of pituitary GH isoforms; after injection of recombinant human GH, which comprises solely the 22-kDa isoform, endogenous production is down-regulated leading to an increase in the 22-kDa isoform relative to other isoforms. The second is based on measurement of markers of GH action. Insulin-like growth factor-I (IGF-I) and N-terminal pro-peptide of type III collagen (P-III-NP) increase in response to GH administration in a dose-dependent manner. When combined with discriminant function analysis, use of these markers differentiates between individuals taking GH and placebo. Subsequent studies have shown that the test is applicable across different ethnicities and is unaffected by injury. WADA regulations state that when analytes are measured by immunoassay, two assays are needed. Final validation of the marker test is currently being undertaken with modern commercially available immunoassays to finalise the threshold values to be used to determine whether a doping offence has been committed.

  8. Towards engineering hormone-binding globulins as drug delivery agents.

    PubMed

    Chan, Wee Lee; Zhou, Aiwu; Read, Randy J

    2014-01-01

    The treatment of many diseases such as cancer requires the use of drugs that can cause severe side effects. Off-target toxicity can often be reduced simply by directing the drugs specifically to sites of diseases. Amidst increasingly sophisticated methods of targeted drug delivery, we observed that Nature has already evolved elegant means of sending biological molecules to where they are needed. One such example is corticosteroid binding globulin (CBG), the major carrier of the anti-inflammatory hormone, cortisol. Targeted release of cortisol is triggered by cleavage of CBG's reactive centre loop by elastase, a protease released by neutrophils in inflamed tissues. This work aimed to establish the feasibility of exploiting this mechanism to carry therapeutic agents to defined locations. The reactive centre loop of CBG was altered with site-directed mutagenesis to favour cleavage by other proteases, to alter the sites at which it would release its cargo. Mutagenesis succeeded in making CBG a substrate for either prostate specific antigen (PSA), a prostate-specific serine protease, or thrombin, a key protease in the blood coagulation cascade. PSA is conspicuously overproduced in prostatic hyperplasia and is, therefore, a good way of targeting hyperplastic prostate tissues. Thrombin is released during clotting and consequently is ideal for conferring specificity to thrombotic sites. Using fluorescence-based titration assays, we also showed that CBG can be engineered to bind a new compound, thyroxine-6-carboxyfluorescein, instead of its physiological ligand, cortisol, thereby demonstrating that it is possible to tailor the hormone binding site to deliver a therapeutic drug. In addition, we proved that the efficiency with which CBG releases bound ligand can be increased by introducing some well-placed mutations. This proof-of-concept study has raised the prospect of a novel means of targeted drug delivery, using the serpin conformational change to combat the problem of

  9. Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents

    PubMed Central

    Chan, Wee Lee; Zhou, Aiwu; Read, Randy J.

    2014-01-01

    The treatment of many diseases such as cancer requires the use of drugs that can cause severe side effects. Off-target toxicity can often be reduced simply by directing the drugs specifically to sites of diseases. Amidst increasingly sophisticated methods of targeted drug delivery, we observed that Nature has already evolved elegant means of sending biological molecules to where they are needed. One such example is corticosteroid binding globulin (CBG), the major carrier of the anti-inflammatory hormone, cortisol. Targeted release of cortisol is triggered by cleavage of CBG's reactive centre loop by elastase, a protease released by neutrophils in inflamed tissues. This work aimed to establish the feasibility of exploiting this mechanism to carry therapeutic agents to defined locations. The reactive centre loop of CBG was altered with site-directed mutagenesis to favour cleavage by other proteases, to alter the sites at which it would release its cargo. Mutagenesis succeeded in making CBG a substrate for either prostate specific antigen (PSA), a prostate-specific serine protease, or thrombin, a key protease in the blood coagulation cascade. PSA is conspicuously overproduced in prostatic hyperplasia and is, therefore, a good way of targeting hyperplastic prostate tissues. Thrombin is released during clotting and consequently is ideal for conferring specificity to thrombotic sites. Using fluorescence-based titration assays, we also showed that CBG can be engineered to bind a new compound, thyroxine-6-carboxyfluorescein, instead of its physiological ligand, cortisol, thereby demonstrating that it is possible to tailor the hormone binding site to deliver a therapeutic drug. In addition, we proved that the efficiency with which CBG releases bound ligand can be increased by introducing some well-placed mutations. This proof-of-concept study has raised the prospect of a novel means of targeted drug delivery, using the serpin conformational change to combat the problem of

  10. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance.

    PubMed

    Nyberg, F

    2000-10-01

    During the past decade studies have shown that growth hormone (GH) may exert profound effects on the central nervous system (CNS). For instance, GH replacement therapy was found to improve the psychological capabilities in adult GH deficient (GHD) patients. Furthermore, beneficial effects of the hormone on certain functions, including memory, mental alertness, motivation, and working capacity, have been reported. Likewise, GH treatment of GHD children has been observed to produce significant improvement in many behavioral problems seen in these individuals. Studies also indicated that GH therapy affects the cerebrospinal fluid levels of various hormones and neurotransmitters. Further support that the CNS is a target for GH emerges from observations indicating that the hormone may cross the blood-brain barrier (BBB) and from studies confirming the presence of GH receptors in the brain. It was previously shown that specific binding sites for GH are present in discrete areas in the CNS of both humans and rats. Among these regions are the choroid plexus, hippocampus, hypothalamus, and spinal cord. The density of GH binding in the various brain regions was found to decline with increasing age. More recently, we were able to clone and determine the structure of several GH receptors in the rat and human brain. Although the brain receptor proteins for the hormone were shown to differ in molecular size compared to those present in peripheral tissues the corresponding transcripts did not seem to differ from their peripheral congeners. GH receptors in the hypothalamus are likely to be involved in the regulatory mechanism for hormone secretion and those located in the choroid plexus have been suggested to have a role in the receptor-mediated transport of GH across the BBB. The functions mediated by the GH receptors identified in the hippocampus are not yet known but recently it was speculated that they may be involved in the hormone's action on memory and cognitive functions.

  11. Growth hormone, insulin-like growth factor system and carcinogenesis.

    PubMed

    Boguszewski, Cesar Luiz; Boguszewski, Margaret Cristina da Silva; Kopchick, John J

    2016-01-01

    The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414-426). PMID:27387246

  12. Growth hormone assays: current methodologies and their limitations.

    PubMed

    Bidlingmaier, Martin; Strasburger, Christian J

    2007-01-01

    Measurement of circulating growth hormone (GH) concentrations is essential in diagnosis of either GH deficiency or GH excess. The invention of immunoassays for the measurement of peptide hormones was a major breakthrough, enabling the routine analysis of GH concentrations in larger series of samples. Over the last few decades, measurement technology has evolved from less sensitive, mainly radioactive assays based on polyclonal antisera to the latest generations of highly sensitive chemiluminescence methods employing monoclonal antibodies. Unfortunately, the development of newer assays did not lead to better agreement among the results obtained by different assay methods. On the contrary, the differences tended to increase when monoclonal antibody based assays became more popular. The actual value reported for the GH concentration in a specific patient's sample still mainly depends on the method used by the respective laboratory, limiting the applicability of international consensus guidelines in clinical practice. The heterogeneity of the analyte itself, the availability of different reference preparations for calibration and the interference from matrix components such as GH binding protein are among the reasons why standardizing GH assays is difficult. An additional challenge arose from the availability of a GH receptor antagonist for the treatment of acromegaly, which is basically a mutated form of GH and therefore interferes in many GH assays. This review provides an overview on GH assays used in clinical practice, their limitations and the potential next steps towards standardization.

  13. Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein.

    PubMed Central

    Muñoz, A; Zenke, M; Gehring, U; Sap, J; Beug, H; Vennström, B

    1988-01-01

    To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone-independent activity of P75gag-v-erbA provided a selective advantage to the avian erythroblastosis virus during the original selection for a highly oncogenic strain of the virus. Images PMID:3359993

  14. Growth hormone treatment in non-growth hormone-deficient children

    PubMed Central

    Carta, Luisanna; Ibba, Anastasia; Guzzetti, Chiara

    2014-01-01

    Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD). With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition. PMID:24926456

  15. Growth hormone treatment in non-growth hormone-deficient children.

    PubMed

    Loche, Sandro; Carta, Luisanna; Ibba, Anastasia; Guzzetti, Chiara

    2014-03-01

    Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD). With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition. PMID:24926456

  16. Characterization of growth hormone and prolactin produced by human pituitary in culture.

    PubMed

    Skyler, J S; Rogol, A D; Lovenberg, W; Knazek, R A

    1977-02-01

    Fragments of a pituitary tumor from a patient with acromegaly were grown in tissue culture. The tumor secreted both growth hormone and prolactin,which were recovered in high concentrations. The nonpurified hormones were characterized and compared to their respective counterparts obtained by extraction from normal pituitaries obtained at autopsy. The tissue culture and pituitary extracted hormones were eluted from Sephadex G-100 with the same partition coefficients. Growth hormone from both sources showed parallel dose-response displacement curves, by logit-log transformation, in both specific immunoassay and in a specific lymphocyte binding assay. Prolactin from both sources was compared in specific immunoassay using three different antisera. Parallel logit-log displacement curves were seen with one antiserum, while the other two antisera yielded non-parallel curves, indicating structural differences between prolactin from the two sources. Quantitative polyacrylamide gel electrophoresis was performed using multiphasic buffer systems previously developed for characterization of each hormone. By the criteria of joint 95% confidence envelopes of retardation co-efficient and relative free mobility, tissue culture growth hormone and prolactin were indistinguishable from their pituitary-extracted counterparts. This study demonstrates that, prior to purification, tissue culture derived hormone can be characterized by multiple criteria and compared to a standard preparation. Structural differences can be detected, as in the case of prolactin. When the hormones are indistinguishable, as in the case of growth hormone, it becomes worthwhile to increase the scale of tissue cultured production, with the prospect that tissue culture may serve as a source of hormone for both experimental and therapeutic use.

  17. Growth hormone producing prolactinoma in juvenile cystinosis: a simple coincidence?

    PubMed Central

    Besouw, Martine T. P.; Willemsen, Michèl A. A. P.; Noordam, Kees

    2007-01-01

    Juvenile cystinosis was diagnosed in a patient who presented with severe headache attacks and photophobia. Treatment with oral cysteamine and topical cysteamine eye drops was started. One-and-a-half years later, he developed unilateral gynecomastia and elevated prolactin and growth hormone levels. A pituitary macroprolactinoma was discovered and successfully treated with the dopamine agonist cabergoline. Increased serum growth hormone levels were attributed to enhanced growth hormone production by the prolactinoma and somatostatin inhibition by cysteamine. Although the occurrence of prolactinoma in this patient could be a simple coincidence, it might also be a rare yet unrecognised complication of cystinosis. PMID:17638022

  18. [Growth hormone receptor antagonist in the treatment of acromegaly].

    PubMed

    Hubina, Erika; Tóth, Agnes; Kovács, Gábor László; Dénes, Judit; Kovács, László; Góth, Miklós

    2011-05-01

    Exploration of construction, function and interaction of human growth hormone and growth hormone receptor in details resulted in the innovation of the new growth hormone receptor antagonist, pegvisomant. Pegvisomant with different mechanism of action extended the tools of medical management of acromegaly. Importance of the novel treatment modality is high. In one hand the necessity of the strict control of growth hormone/insulin-like growth factor-I axis has been proven regarding the mortality of the disease. On the other hand, despite the use of all current modes of treatment (surgery, radiotherapy, dopamine agonists, somatostatin analogs), a significant cohort of patients with acromegaly remains inadequately controlled. Pegvisomant has been registered in 2004. Since 2006, it has been used in Hungary for the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. Clinical use of pegvisomant in the treatment of acromegaly is effective, well tolerated, and safe, based on international Acrostudy database. In order to improve the efficacy of therapy clinical trials started with pegvisomant and somatostatin analog combination treatment. Evidence of several further effects of the growth hormone/insulin-like growth factor-I axis suggests other potential uses of growth hormone receptor antagonists. PMID:21498159

  19. Growth hormone replacement in patients with Langerhan's cell histiocytosis

    PubMed Central

    Howell, S; Wilton, P; Shalet, S

    1998-01-01

    OBJECTIVES—To assess the impact of growth hormone on growth and the underlying disease in children with growth hormone deficiency as a result of Langerhan's cell histiocytosis.
STUDY DESIGN—Retrospective analysis of data from the Kabi (Pharmacia & Upjohn) international growth database (KIGS) for 82 children with Langerhan's cell histiocytosis treated with recombinant growth hormone.
RESULTS—At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7) years, with a median height standard deviation score (SDS) of −2.0 (−3.5 to −0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9 to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with growth hormone, and then remained significantly greater than the pretreatment height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second and third years, respectively. The median height SDS increased from −2.0 to −0.8 (−2.3 to 0.6) by the end of three years of treatment. There was no increase in the recurrence rate of the underlying disease and no adverse event could be directly attributed to growth hormone treatment, apart from one case of benign intracranial hypertension that resolved on stopping treatment with growth hormone.
CONCLUSIONS—Growth hormone replacement treatment for patients with Langerhan's cell histiocytosis with growth hormone deficiency is beneficial and safe.

 PMID:9659097

  20. Significance of the disulphide bonds of human growth hormone.

    PubMed

    Junnila, Riia K; Kopchick, John J

    2013-01-01

    Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders. PMID:24002958

  1. Growth Hormone and Insulin-Like Growth Factor-1.

    PubMed

    Nicholls, Adam R; Holt, Richard I G

    2016-01-01

    Human growth hormone (GH) was first isolated from the human pituitary gland in 1945 and found to promote the growth of children with hypopituitarism. Since the formation of the World Anti-Doping Association, human GH has appeared on the list of forbidden substances. There is a significant amount of anecdotal evidence that human GH is misused by athletes to enhance performance, and there have been a number of high-profile cases of GH use in professional sport. GH secretagogues (GH-Ss), which increase GH secretion, and insulin-like growth factor (IGF-1), which mediates many of the effects of GH, are also misused, although there is less evidence for this. The effectiveness of GH, IGF-1, and GH-Ss as performance-enhancing drugs remains unclear. Evidence from studies of GH use in people with hypopituitarism show several desirable outcomes, including increased lean body mass, increased strength, and increased exercise capacity. These anabolic and metabolic properties, coupled with the difficulty in detecting them, make them attractive as agents of misuse. Studies in healthy young adults have also demonstrated a performance benefit with GH and IGF-1. PMID:27347885

  2. New detection methods of growth hormone and growth factors.

    PubMed

    Bidlingmaier, Martin

    2012-01-01

    Human growth hormone (GH), but also GH related growth factors like the insulin-like growth factor-1 (IGF-1) are known to be abused in sports. Although the scientific evidence supporting a distinct effect of GH on performance in healthy trained subjects is limited, it has been repeatedly found with athletes or trainers, and the recent introduction of a first test to detect GH doping has led to a number of positive cases. Currently, there is no test for the detection of IGF-1 introduced worldwide, but confiscation of the drug from sports teams can be taken as indirect evidence for its abuse. The major biochemical difficulty for the detection of GH is that the recombinant form is identical in physicochemical properties to the endogenous GH secreted by the pituitary gland. Furthermore, the very short half-life of GH in circulation inherently shortens the window of opportunity where the drug can be detected. Two strategies have been followed for more than a decade to develop a test to detect the application of recombinant GH: the marker approach, which is based on the elevation of GH-dependent markers above the level seen under physiological conditions evoked by administration of recombinant GH, and the isoform approach, which is based on a change in the pattern of GH isoforms in circulation following the injection of recombinant GH.

  3. Effect of growth hormone on protein phosphorylation in isolated rat hepatocytes

    SciTech Connect

    Yamada, K.; Lipson, K.E.; Marino, M.W.; Donner, D.B.

    1987-02-10

    Hepatocytes from male rats were incubated with (/sup 32/P)P/sub i/ for 40 min at 37/sup 0/C, thereby equilibrating the cellular ATP pool with /sup 32/P. Subsequent exposure to bovine growth hormone for 10 additional min did not change the specific activity of cellular (..gamma..-/sup 32/P)ATP. Two-dimensional gel electrophoresis or chromatofocusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to fractionate phosphoproteins solubilized from control or hormone-stimulated cells. Stimulation of hepatocytes with 5 nM growth hormone for 10 min at 37/sup 0/C affected the phosphorylation of a number of proteins including an M/sub r/ 46,000 species of pI 4.7 whose phosphorylation was augmented (2.65 +/- 0.50)-fold. A significant fraction of the maximal effect of growth hormone on phosphorylation of the M/sub r/ 46,000 species was elicited by 1-5% receptor occupancy. Bovine growth hormone, which binds to somatogenic receptors with great specificity, or recombinant human growth hormone, which is not contaminated with other hormones, affected phosphorylation of hepatic proteins similarly. The M/sub r/ 46,000 phosphoprotein was isolated in a fraction enriched in cytosol after centrifugation of cellular homogenates. Phosphorylation of the M/sub r/ 46,000 phosphoprotein was also increased (1.75 +/- 0.35)-fold and (2.15 +/- 0.50)-fold by insulin and glucagon, respectively. These observations are consistent with the possibility that selective changes in the phosphorylation state of cellular proteins may mediate growth hormone actions in cells.

  4. Growth hormone is permissive for neoplastic colon growth.

    PubMed

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Recouvreux, Maria Victoria; Ben-Shlomo, Anat; Araki, Takako; Barrett, Robert; Workman, Michael; Wawrowsky, Kolja; Ljubimov, Vladimir A; Uhart, Magdalena; Melmed, Shlomo

    2016-06-01

    Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals. p53 was also induced in skin fibroblasts derived from short-statured humans with mutant GHR. GH-deficient prophet of pituitary-specific positive transcription factor 1 (Prop1)(-/-) mice exhibited induced colon p53 levels, and cross-breeding them with Apc(min+/-) mice that normally develop intestinal and colon tumors resulted in GH-deficient double mutants with markedly decreased tumor number and size. We also demonstrate that GH suppresses p53 and reduces apoptosis in human colon cell lines as well as in induced human pluripotent stem cell-derived intestinal organoids, and confirm in vivo that GH suppresses colon mucosal p53/p21. GH excess leads to decreased colon cell phosphatase and tensin homolog deleted on chromosome 10 (PTEN), increased cell survival with down-regulated APC, nuclear β-catenin accumulation, and increased epithelial-mesenchymal transition factors and colon cell motility. We propose that GH is a molecular component of the "field change" milieu permissive for neoplastic colon growth. PMID:27226307

  5. Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.

    PubMed

    Renehan, Andrew G; Solomon, Mattea; Zwahlen, Marcel; Morjaria, Reena; Whatmore, Andrew; Audí, Laura; Binder, Gerhard; Blum, Werner; Bougnères, Pierre; Santos, Christine Dos; Carrascosa, Antonio; Hokken-Koelega, Anita; Jorge, Alexander; Mullis, Primus E; Tauber, Maïthé; Patel, Leena; Clayton, Peter E

    2012-05-01

    Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability = 0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95% credible interval (CrI): 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI: 0.10, 0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.

  6. Evolutionary aspects of growth hormones and prolactins and their receptors

    SciTech Connect

    Tarpey, J.F.

    1986-01-01

    The interactions of GH's, PRL's and PL's with receptors for GH and PRL were examined from a comparative and evolutionary viewpoint. The binding of /sup 125/I-bGH to membrane preparations from liver of representatives of the major classes of non-mammalian vertebrates was also studied. Only hepatic membranes from sturgeon and Gillichthys had significant bGH binding and were further characterized and compared with male rabbit liver membranes in terms of time, temperature, pH, and membrane concentration to optimize binding conditions. The binding of several members of the GH, PRL, PL family of hormones to GH receptors from liver of sturgeon, Gillichthys, rabbit, mouse and rat was investigated. in terms of hormonal specificity, the mammalian receptors and the sturgeon binding sites were similar, while Gillichthys receptors had a different pattern of hormonal specificity. The binding of /sup 125/I-oPRL to renal membranes of the turtle, Pseudemys scripta elegans, was characterized and compared to PRL binding sites of kidney membranes of the bullfrog, Rana catesbeiana, and the tiger salamander, Ambystoma tigrinum.

  7. Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment.

    PubMed

    Butler, Merlin G; Lee, Jaehoon; Cox, Devin M; Manzardo, Ann M; Gold, June-Anne; Miller, Jennifer L; Roof, Elizabeth; Dykens, Elisabeth; Kimonis, Virginia; Driscoll, Daniel J

    2016-09-01

    The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone-treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non-growth hormone-treated PWS individuals. Growth chart implications and recommended usage are discussed. PMID:26842920

  8. Thyroid hormones in fetal growth and prepartum maturation.

    PubMed

    Forhead, A J; Fowden, A L

    2014-06-01

    The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

  9. [Benefits and risks of growth hormone in adults with growth hormone deficiency].

    PubMed

    Díez, Juan J; Cordido, Fernando

    2014-10-21

    Adult growth hormone (GH) deficiency is a well-recognized clinical syndrome with adverse health consequences. Many of these may improve after replacement therapy with recombinant GH. This treatment induces an increase in lean body mass and a decrease in fat mass. In long-term studies, bone mineral density increases and muscle strength improves. Health-related quality of life tends to increase after treatment with GH. Lipid profile and markers of cardiovascular risk also improve with therapy. Nevertheless, GH replacement therapy is not without risk. According to some studies, GH increases blood glucose, body mass index and waist circumference and may promote long-term development of diabetes and metabolic syndrome. Risk of neoplasia does not appear to be increased in adults treated with GH, but there are some high-risk subgroups. Methodological shortcomings and difficulties inherent to long-term studies prevent definitive conclusions about the relationship between GH and survival. Therefore, research in this field should remain active.

  10. Adult Growth Hormone Deficiency – Benefits, Side Effects, and Risks of Growth Hormone Replacement

    PubMed Central

    Reed, Mary L.; Merriam, George R.; Kargi, Atil Y.

    2013-01-01

    Deficiency of growth hormone (GH) in adults results in a syndrome characterized by decreased muscle mass and exercise capacity, increased visceral fat, impaired quality of life, unfavorable alterations in lipid profile and markers of cardiovascular risk, decrease in bone mass and integrity, and increased mortality. When dosed appropriately, GH replacement therapy (GHRT) is well tolerated, with a low incidence of side effects, and improves most of the alterations observed in GH deficiency (GHD); beneficial effects on mortality, cardiovascular events, and fracture rates, however, remain to be conclusively demonstrated. The potential of GH to act as a mitogen has resulted in concern over the possibility of increased de novo tumors or recurrence of pre-existing malignancies in individuals treated with GH. Though studies of adults who received GHRT in childhood have produced conflicting reports in this regard, long-term surveillance of adult GHRT has not demonstrated increased cancer risk or mortality. PMID:23761782

  11. Pathology of growth hormone-producing tumors of the human pituitary.

    PubMed

    Kovacs, K; Horvath, E

    1986-02-01

    This paper reviews the morphologic features of growth hormone-producing tumors of the human pituitary. These tumors are associated with elevated blood growth hormone levels and acromegaly or gigantism and can be classified into the following morphologically distinct entities by the combined application of histology, immunocytology, and electron microscopy: densely granulated growth hormone cell adenoma; sparsely granulated growth hormone cell adenoma; mixed growth hormone cell- prolactin cell-adenoma; acidophil stem cell adenoma; mammosomatotroph cell adenoma; growth hormone cell carcinoma; plurihormonal adenoma with growth hormone production. PMID:3303228

  12. Identification and characterization of growth hormone receptors in snakehead fish (Ophiocephalus argus cantor) liver.

    PubMed

    Sun, X; Zhu, S; Chan, S S; Toresson, G; Cheng, C H

    1997-12-01

    The specific binding of 125I-labeled fish growth hormone (GH) to hepatic membranes prepared from several freshwater fish was assessed. A high level of growth hormone receptor (GHR) was detected on the hepatic membranes of the snakehead fish (Ophiocephalus argus Cantor). Scatchard analysis of the binding data showed a single class of high affinity binding site with a binding affinity (Ka) of 1.45 +/- 0.23 x 10(9) M-1 and a binding capacity (Bmax) of 198 +/- 57 fmol/mg protein. The binding was specific for fish GH and was saturable. In addition, the specific binding was temperature- and time-dependent, reaching a steady state after 16 hr of incubation at 25 degrees . The molecular weight of GHR as measured by Sephadex G-200 column chromatography and Western blot analysis using a monoclonal antibody (Mab263) against GHR was found to be 200-400 and 90-93 kDa, respectively. Two bands at 65 and 89 kDa were identified in ligand crosslinking studies of membrane receptors. A sensitive teleost GH radioreceptor assay (RRA) was developed, using recombinant fish GH and a membrane preparation from snakehead fish liver, capable of measuring bioactive GH in fish sera or other samples.

  13. Ethylene and Hormonal Cross Talk in Vegetative Growth and Development.

    PubMed

    Van de Poel, Bram; Smet, Dajo; Van Der Straeten, Dominique

    2015-09-01

    Ethylene is a gaseous plant hormone that most likely became a functional hormone during the evolution of charophyte green algae, prior to land colonization. From this ancient origin, ethylene evolved into an important growth regulator that is essential for myriad plant developmental processes. In vegetative growth, ethylene appears to have a dual role, stimulating and inhibiting growth, depending on the species, tissue, and cell type, developmental stage, hormonal status, and environmental conditions. Moreover, ethylene signaling and response are part of an intricate network in cross talk with internal and external cues. Besides being a crucial factor in the growth control of roots and shoots, ethylene can promote flowering, fruit ripening and abscission, as well as leaf and petal senescence and abscission and, hence, plays a role in virtually every phase of plant life. Last but not least, together with jasmonates, salicylate, and abscisic acid, ethylene is important in steering stress responses.

  14. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1984-01-01

    A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

  15. Human growth hormone and the development of osteochondritis dissecans lesions.

    PubMed

    Hussain, Waqas M; Hussain, Haroon M; Hussain, Mohammed S; Ho, Sherwin S W

    2011-12-01

    No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.

  16. Plasma variation of corticosteroid-binding globulin and sex hormone-binding globulin.

    PubMed

    Lewis, J G; Möpert, B; Shand, B I; Doogue, M P; Soule, S G; Frampton, C M; Elder, P A

    2006-04-01

    Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) circulate in plasma and bind their cognate ligands with high affinity, offering a steroid delivery system to target tissues by a variety of mechanisms. Analysis of these steroid-binding proteins is gaining importance in the clinical setting, although more information is warranted on their diurnal and biological variation. This study shows that plasma SHBG (in normal subjects) exhibits little diurnal or biological variation over the 30 day period studied, in contrast to CBG, where plasma levels peak in the early afternoon. This leads to attenuation of the diurnal free cortisol level rhythm compared to total cortisol. We also show that plasma CBG is significantly lower in male subjects with the metabolic syndrome compared to age-matched lean counterparts, and may therefore act as a surrogate marker of insulin resistance. The consequence of lower levels of CBG in these obese male subjects is reflected by higher levels of circulating free cortisol, potentially offering a more favourable environment for adipogenesis.

  17. Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

    PubMed Central

    Kim, Youngsook; Hong, Jae Won; Chung, Yoon-Sok; Kim, Sung-Woon; Cho, Yong-Wook; Kim, Jin Hwa; Kim, Byung-Joon

    2014-01-01

    Purpose The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated. Materials and Methods This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. Results The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. Conclusion Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events. PMID:24954335

  18. Structural basis for cyclodextrins' suppression of human growth hormone aggregation

    PubMed Central

    Otzen, Daniel Erik; Knudsen, Benjamin Raerup; Aachmann, Finn; Larsen, Kim Lambertsen; Wimmer, Reinhard

    2002-01-01

    Many therapeutic proteins require storage at room temperature for extended periods of time. This can lead to aggregation and loss of function. Cyclodextrins (CDs) have been shown to function as aggregation suppressors for a wide range of proteins. Their potency is often ascribed to their affinity for aromatic amino acids, whose surface exposure would otherwise lead to protein association. However, no detailed structural studies are available. Here we investigate the interactions between human growth hormone (hGH) and different CDs at low pH. Although hGH aggregates readily at pH 2.5 in 1 M NaCl to form amorphous aggregates, the presence of 25 to 50 mM of various β-CD derivatives is sufficient to completely avoid this. α- and γ-CD are considerably less effective. Stopped-flow data on the aggregation reaction in the presence of β-CD are analyzed according to a minimalist association model to yield an apparent hGH-β-CD dissociation constant of ∼6 mM. This value is very similar to that obtained by simple fluorescence-based titration of hGH with β-CD. Nuclear magnetic resonance studies indicate that β-CD leads to a more unfolded conformation of hGH at low pH and predominantly binds to the aromatic side-chains. This indicates that aromatic amino acids are important components of regions of residual structure that may form nuclei for aggregation. PMID:12070330

  19. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

    NASA Technical Reports Server (NTRS)

    Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

    1999-01-01

    Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

  20. Hormonal regulation of wheat growth during hydroponic culture

    NASA Technical Reports Server (NTRS)

    Wetherell, Donald

    1988-01-01

    Hormonal control of root growth has been explored as one means to alleviate the crowding of plant root systems experienced in prototype hydroponic biomass production chambers being developed by the CELSS Breadboard Project. Four plant hormones, or their chemical analogs, which have been reported to selectively inhibit root growth, were tested by adding them to the nutrient solutions on day 10 of a 25 day growth test using spring wheat in hydroponic cultures. Growth and morphological changes is both shoot and root systems were evaluated. In no case was it possible to inhibit root growth without a comparable inhibition of shoot growth. It was concluded that this approach is unlikely to prove useful for wheat.

  1. Regulation of human growth hormone secretion and its disorders.

    PubMed

    Kato, Yuzuru; Murakami, Yoshio; Sohmiya, Motoi; Nishiki, Masateru

    2002-01-01

    Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GH releasing hormone (GHRH), somatostatin (SRIF), GH releasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GH secretion are neural endogenous rhythm, sleep, stress, exercise, and nutritional and metabolic signals. GH deficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GH deficiency can be treated with recombinant human GH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GH hypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GH can be treated by transshenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GH secretion in combination with or without the surgery. PMID:11838603

  2. Effects of growth hormone overexpression and growth hormone resistance on neuroendocrine and reproductive functions in transgenic and knock-out mice.

    PubMed

    Bartke, A; Chandrashekar, V; Turyn, D; Steger, R W; Debeljuk, L; Winters, T A; Mattison, J A; Danilovich, N A; Croson, W; Wernsing, D R; Kopchick, J J

    1999-11-01

    Transgenic mice overexpressing growth hormone (GH) exhibit alterations in the function of the hypothalamic-pituitary-gonadal (HPG) axis and the H-P-adrenal axis. Alterations in the turnover of hypothalamic neurotransmitters, in plasma hormone levels, and in regulation of their release are associated with reproductive deficits, particularly in females. Results reported after publication of our minireview on this subject provided evidence that GH-transgenic mice have increased binding of GH to GH binding proteins in plasma, are hyperinsulinemic and insulin resistant, and have major alterations in energy budgets with increased allocation to growth. Reduced life span and fertility of these animals may be related to insufficient allocation of energy to reproduction and maintenance. Growth hormone resistance induced by transgenic expression of an antagonistic bGH analog or by targeted disruption (knock-out, KO) of the GH receptor (GH-R) gene leads to dramatic suppression of plasma levels of insulin-like growth factor-1 (IGF-1), and dwarf phenotype due to reduced growth and increased adiposity. In both models of GH resistance, there are marked reproductive deficits in females, decline of breeding performance of males, and alterations in the function of the HPG axis. In GH-R-KO females, puberty is delayed, and litter size is reduced. Fetal weights are reduced whereas placental weights are increased, and the weight of newborn pups is reduced despite an increase in the length of gestation. In GH-R-KO males, copulatory behavior and fertility are reduced, plasma PRL is elevated, and responses to luteinizing hormone releasing hormone (LHRH) in vivo and to LH in vitro are suppressed. However, reproductive deficits in GH-R-KO mice are very mild when compared to those described previously in IGF-KO animals. Apparently, the amounts of IGF-1 that may be produced locally in the absence of GH stimulation are sufficient for sexual maturation and fertility in both sexes, whereas

  3. Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network.

    PubMed

    Redelman, Doug; Welniak, Lisbeth A; Taub, Dennis; Murphy, William J

    2008-01-01

    Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins.

  4. Impaired hair growth and wound healing in mice lacking thyroid hormone receptors.

    PubMed

    Contreras-Jurado, Constanza; García-Serrano, Laura; Martínez-Fernández, Mónica; Ruiz-Llorente, Lidia; Paramio, Jesus M; Aranda, Ana

    2014-01-01

    Both clinical and experimental observations show that the skin is affected by the thyroidal status. In hypothyroid patients the epidermis is thin and alopecia is common, indicating that thyroidal status might influence not only skin proliferation but also hair growth. We demonstrate here that the thyroid hormone receptors (TRs) mediate these effects of the thyroid hormones on the skin. Mice lacking TRα1 and TRβ (the main thyroid hormone binding isoforms) display impaired hair cycling associated to a decrease in follicular hair cell proliferation. This was also observed in hypothyroid mice, indicating the important role of the hormone-bound receptors in hair growth. In contrast, the individual deletion of either TRα1 or TRβ did not impair hair cycling, revealing an overlapping or compensatory role of the receptors in follicular cell proliferation. In support of the role of the receptors in hair growth, TRα1/TRβ-deficient mice developed alopecia after serial depilation. These mice also presented a wound-healing defect, with retarded re-epithelialization and wound gaping, associated to impaired keratinocyte proliferation. These results reinforce the idea that the thyroid hormone nuclear receptors play an important role on skin homeostasis and suggest that they could be targets for the treatment of cutaneous pathologies.

  5. Parathyroid hormone and growth in chronic kidney disease.

    PubMed

    Waller, Simon

    2011-02-01

    Growth failure is common in children with chronic kidney disease, and successful treatment is a major challenge in the management of these children. The aetiology is multi-factorial with "chronic kidney disease-metabolic bone disorder" being a key component that is particularly difficult to manage. Parathyroid hormone is at the centre of this mineral imbalance, consequent skeletal disease and, ultimately, growth failure. When other aetiologies are treated, good growth can be achieved throughout the course of the disease when parathyroid hormone (PTH) levels are in the normal range or slightly elevated. A direct correlation between PTH levels and growth has not been convincingly established, and the direct effect of PTH on growth has not been adequately described; furthermore, direct actions of PTH on the growth plate are unproven. The effects of PTH on growth stem from the pivotal role that PTH plays in the development of renal osteodystrophy. In severe secondary hyperparathyroidism, the growth plate is altered and growth is affected. At the other end of the spectrum, with an over-suppressed parathyroid gland, the rate of bone turnover and remodelling is markedly diminished, and some data suggest this is associated with poor growth. Most of the data available suggests that avoiding the development of significant bone disease through the strict control of PTH levels permits good growth. Absolute optimal ranges for PTH that maximise growth or minimise growth failure are not yet established.

  6. GH responses to growth hormone releasing factor in depression.

    PubMed

    Thomas, R; Beer, R; Harris, B; John, R; Scanlon, M

    1989-01-01

    The growth hormone (GH), thyrotrophin (TSH) and prolactin response to growth hormone releasing factor (GRF) was investigated in 18 patients suffering from major depression with melancholia and in 18 age- and sex-matched normal controls. There was no significant difference in the GH response to GRF stimulation between the patients and controls and in neither subject group was there a demonstrable TSH or prolactin response to GRF. These findings indicate that the pathophysiology underlying the blunted GH response to pharmacological challenge, demonstrated in other studies, must lie at a suprapituitary level.

  7. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  8. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  9. Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

    PubMed Central

    Hou, Ling; Chen, Zhi-hang; Liu, Dong; Cheng, Yuan-guo; Luo, Xiao-ping

    2016-01-01

    Objective Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH. Design and methods Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w. Results In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher Cmax, significantly longer half-life (t1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC(0–∞)7th/AUC(0–∞)1st) of rhGH was 1.02, while the AUC(0–∞)6th/AUC(0–∞)1st of Jintrolong ® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial. Conclusion The elimination rate of Jintrolong® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong® is suitable for long-term growth hormone treatment in children with growth hormone deficiency. PMID:26719670

  10. Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome.

    PubMed Central

    Duquesnoy, P; Sobrier, M L; Amselem, S; Goossens, M

    1991-01-01

    Mutations in the growth hormone receptor (GHR) gene can cause growth hormone (GH) resistance. Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism. We have previously identified a mutation within the extracellular domain of this receptor, replacing phenylalanine by serine at position 96 of the mature protein, in a patient with Laron syndrome. We have now investigated the effect of this Phe----Ser substitution on hormone binding activity by expressing the total human GHR cDNA and mutant form in eukaryotic cells. The wild-type protein expressed was able to bind GH but no plasma membrane binding was detectable on cells transfected with the mutant cDNA; this was also the case of cells transfected with a Phe96----Ala mutant cDNA, suggesting that the lack of binding activity is not due to a posttranslational modification of serine. Examination of the variant proteins in subcellular fractions revealed the presence of specific GH binding activity in the lysosomal fraction, whereas immunofluorescence studies located mutant proteins in the cytosol. Our findings suggest that these mutant GHRs fail to follow the correct intracellular transport pathway and underline the potential importance of this phenylalanine residue, which is conserved among the GH, prolactin, and erythropoietin receptors that belong to the same cytokine receptor superfamily. Images PMID:1719554

  11. Usability and Tolerability of the Norditropin NordiFlex® Injection Device in Children Never Previously Treated With Growth Hormone

    ClinicalTrials.gov

    2014-06-23

    Growth Hormone Disorder; Growth Hormone Deficiency in Children; Genetic Disorder; Turner Syndrome; Foetal Growth Problem; Small for Gestational Age; Chronic Kidney Disease; Chronic Renal Insufficiency; Delivery Systems

  12. Effects of hypothalamic dopamine on growth hormone-releasing hormone-induced growth hormone secretion and thyrotropin-releasing hormone-induced prolactin secretion in goats.

    PubMed

    Jin, Jin; Hashizume, Tsutomu

    2015-06-01

    The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH-releasing response to an intravenous (i.v.) injection of GH-releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L-dopa (1 mg/kg BW) in male and female goats under a 16-h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L-dopa treatments completely suppressed GH-releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)-releasing response to an i.v. injection of thyrotropin-releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L-dopa significantly reduced TRH-induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats.

  13. Light-Mediated Hormonal Regulation of Plant Growth and Development.

    PubMed

    de Wit, Mieke; Galvão, Vinicius Costa; Fankhauser, Christian

    2016-04-29

    Light is crucial for plant life, and perception of the light environment dictates plant growth, morphology, and developmental changes. Such adjustments in growth and development in response to light conditions are often established through changes in hormone levels and signaling. This review discusses examples of light-regulated processes throughout a plant's life cycle for which it is known how light signals lead to hormonal regulation. Light acts as an important developmental switch in germination, photomorphogenesis, and transition to flowering, and light cues are essential to ensure light capture through architectural changes during phototropism and the shade avoidance response. In describing well-established links between light perception and hormonal changes, we aim to give insight into the mechanisms that enable plants to thrive in variable light environments.

  14. Growth and hormonal status of children treated for brain tumours.

    PubMed

    Shalet, S M

    1982-01-01

    The adult survivors of the treatment of brain tumours in childhood are often short. Several adverse factors contribute to the impaired growth of these children including growth hormone (GH) deficiency, impaired spinal growth following spinal irradiation, chemotherapy, poor nutritional intake and recurrent tumour. The GH deficiency is due to radiation-induced damage to the hypothalamic-pituitary axis. GH is always the first pituitary hormone to be affected by such radiation damage but panhypopituitarism may occur if the radiation dose is sufficiently great. Preliminary results suggest that GH therapy will improve the growth rate of children with radiation-induced GH deficiency. Additional endocrine complications, which may occur following spinal irradiation, include thyroid dysfunction and ovarian failure due to direct radiation damage to the thyroid and the ovary.

  15. Bioluminescent Ligand-Receptor Binding Assays for Protein or Peptide Hormones.

    PubMed

    Liu, Ya-Li; Guo, Zhan-Yun

    2016-01-01

    Bioluminescence has been widely used in biomedical research due to its high sensitivity, low background, and broad linear range. In recent studies, we applied bioluminescence to ligand-receptor binding assays for some protein or peptide hormones based on a newly developed small monomeric Nanoluciferase (NanoLuc) reporter that has the so far brightest bioluminescence. The conventional ligand-receptor binding assays rely on radioligands that have drawbacks, such as radioactive hazards and short shelf lives. In contrast, the novel bioluminescent binding assays use the NanoLuc-based protein or peptide tracers that are safe, stable, and ultrasensitive. Thus, the novel bioluminescent ligand-receptor binding assay would be applied to more and more protein or peptide hormones for ligand-receptor interaction studies in future. In the present article, we provided detailed protocols for setting up the novel bioluminescent ligand-receptor binding assays using two representative protein hormones as examples. PMID:27424896

  16. Growth hormone therapy and craniofacial bones: a comprehensive review.

    PubMed

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth.

  17. Secretory pattern and regulatory mechanism of growth hormone in cattle

    PubMed Central

    2016-01-01

    Abstract The ultradian rhythm of growth hormone (GH) secretion has been known in several animal species for years and has recently been observed in cattle. Although the physiological significance of the rhythm is not yet fully understood, it appears essential for normal growth. In this review, previous studies concerning the GH secretory pattern in cattle, including its ultradian rhythm, are introduced and the regulatory mechanism is discussed on the basis of recent findings. PMID:26260675

  18. [TREATMENT OF SHORT STATURE PATIENTS WITH NOPMAL GROWTH HORMONE SECRETION OF HYPOPHIS].

    PubMed

    Sprinchuk, N A; Samson, O J; Bol'shova, E V

    2014-12-01

    The article presents the treatment outcome in 86 children with short stature associated with different endocrine pathology and saved growth hormone secretion (congenital adrenal hyperplasia chondrodystrophy, Turner syndrome, idiopathic short stature, syndrome biologically inactive growth hormone and other genetically determined pathology). This study extends prior knowledge about the outcomes of the treatment with recombinant growth hormone and luteinizing hormone--releasing hormone analogue (alone or in combination) in short patients with poor prognosis of final height. PMID:26638471

  19. Saccharin and Cyclamate Inhibit Binding of Epidermal Growth Factor

    NASA Astrophysics Data System (ADS)

    Lee, L. S.

    1981-02-01

    The binding of 125I-labeled mouse epidermal growth factor (EGF) to 18 cell lines, including HeLa (human carcinoma), MDCK (dog kidney cells), HTC (rat hepatoma), K22 (rat liver), HF (human foreskin), GM17 (human skin fibroblasts), XP (human xeroderma pigmentosum fibroblasts), and 3T3-L1 (mouse fibroblasts), was inhibited by saccharin and cyclamate. The human cells were more sensitive to inhibition by these sweeteners than mouse or rat cells. EGF at doses far above the physiological levels reversed the inhibition in rodent cells but not in HeLa cells. In HeLa cells, the doses of saccharin and cyclamate needed for 50% inhibition were 3.5 and 9.3 mg/ml, respectively. Glucose, 2-deoxyglucose, sucrose, and xylitol did not inhibit EGF binding. Previous studies have shown that phorbol esters, strongly potent tumor promoters, also inhibit EGF binding to tissue culture cells. To explain the EGF binding inhibition by such greatly dissimilar molecules as phorbol esters, saccharin, and cyclamate, it is suggested that they operate through the activation of a hormone response control unit.

  20. Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice

    SciTech Connect

    Selden, R.F.; Wagner, T.E.; Blethen, S.; Yun, J.S.; Rowe, M.E.; Goodman, H.M. )

    1988-11-01

    The nucleotide sequence of the human growth hormone variant gene, one of the five members of the growth hormone gene family, predicts that it encodes a growth hormone-like protein. As a first step in determining whether this gene is functional in humans, the authors have expressed a mouse methallothionein I/human growth hormone variant fusion gene in mouse L cells and in transgenic mice. The growth hormone variant protein expressed in transiently transfected L cells is distinct from growth hormone itself with respect to reactivity with anti-growth hormone monoclonal antibodies, behavior during column chromatography, and isoelectric point. Transgenic mice expressing the growth hormone variant protein are 1.4- to 1.9-fold larger than nontransgenic controls, suggesting that the protein has growth-promoting properties.

  1. Modified Clonidine Testing for Growth Hormone Stimulation Reveals α2-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency

    PubMed Central

    Willaschek, Christian; Meint, Sebastian; Rager, Klaus; Buchhorn, Reiner

    2015-01-01

    Introduction The association between short stature and increased risk of ischemic heart disease has been subject to studies for decades. The recent discussion of cardiovascular risk during growth hormone therapy has given new importance to this question. We have hypothesized that the autonomic system is a crucial element relating to this subject. Methods Heart rate variability calculated from 24-hour electrocardiogram data is providing insight into the regulatory state of the autonomous nervous system and is an approved surrogate parameter for estimating cardiovascular risk. We have calculated heart rate variability during clonidine testing for growth hormone stimulation of 56 children. As clonidine is a well-known effector of the autonomous system, stimulating vagal tone and decreasing sympathetic activity, we compared the autonomous reactions of children with constitutional growth delay (CGD), growth hormone deficiency (GHD) and former small for gestational age (SGA). Results During clonidine testing children with CGD showed the expected α2-adrenoreceptor mediated autonomous response of vagal stimulation for several hours. This vagal reaction was significantly reduced in the SGA group and nearly non- existent in the GHD group. Discussion Children with GHD show a reduced autonomous response to clonidine indicating α2-adrenoreceptor sub sensitivity. This can be found prior to the start of growth hormone treatment. Since reduction of HRV is an approved surrogate parameter, increased cardiovascular risk has to be assumed for patients with GHD. In the SGA group a similar but less severe reduction of the autonomous response to clonidine was found. These findings may enrich the interpretation of the data on growth hormone therapy, which are being collected by the SAGhE study group. PMID:26361394

  2. Resolving the growth-promoting and metabolic effects of growth hormone: Differential regulation of GH-IGF-I system components.

    PubMed

    Norbeck, Lindsey A; Kittilson, Jeffrey D; Sheridan, Mark A

    2007-05-01

    Growth hormone regulates numerous processes in vertebrates including growth promotion and lipid mobilization. During periods of food deprivation, growth is arrested yet lipid depletion is promoted. In this study, we used rainbow trout on different nutritional regimens to examine the regulation of growth hormone (GH)-insulin-like growth factor-I (IGF-I) system elements in order to resolve the growth-promoting and lipid catabolic actions of GH. Fish fasted for 2 or 6 weeks displayed significantly reduced growth compared to their fed counterparts despite elevated plasma GH, while refeeding for 2 weeks following 4 weeks of fasting partially restored growth and lowered plasma GH. Fish fasted for 6 weeks also exhausted their mesenteric adipose tissue reserves. Sensitivity to GH in the liver was reduced in fasting fish as evidenced by reduced expression of GH receptor type 1 (GHR 1) and GHR 2 mRNAs and by reduced (125)I-GH binding capacity. Expression of GHR 1 and GHR 2 mRNAs also was reduced in the gill of fasted fish. In adipose tissue, however, sensitivity to GH, as indicated by GHR 1 expression and by (125)I-GH binding capacity, increased after 6 weeks of fasting in concert with the observed lipid depletion. Fasting-associated growth retardation was accompanied by reduced expression of total IGF-I mRNA in the liver, adipose and gill, and by reduced plasma levels of IGF-I. Sensitivity to IGF-I was reduced in the gill of fasted fish as indicated by reduced expression of type 1 IGF-I receptor (IGFR 1A and IGFR 1B) mRNAs. By contrast, fasting did not affect expression of IGFR 1 mRNAs or (125)I-IGF-I binding in skeletal muscle and increased expression of IGFR 1 mRNAs and (125)I-IGF-I binding in cardiac muscle. These results indicate that nutritional state differentially regulates GH-IGF-I system components in a tissue-specific manner and that such alterations disable the growth-promoting actions of GH and promote the lipid-mobilizing actions of the hormone.

  3. [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].

    PubMed

    Castell, A-L; Sadoul, J-L; Bouvattier, C

    2013-10-01

    Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented. PMID:24356290

  4. [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].

    PubMed

    Castell, A-L; Sadoul, J-L; Bouvattier, C

    2013-10-01

    Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented.

  5. Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system.

    PubMed

    Khan, Amir S; Sane, David C; Wannenburg, Thomas; Sonntag, William E

    2002-04-01

    There is a large body of evidence that biological aging is related to a series of long-term catabolic processes resulting in decreased function and structural integrity of several physiological systems, among which is the cardiovascular system. These changes in the aging phenotype are correlated with a decline in the amplitude of pulsatile growth hormone secretion and the resulting decrease in plasma levels of its anabolic mediator, insulin like growth factor-1 (IGF-1). The relationship between growth hormone and biological aging is supported by studies demonstrating that growth hormone administration to old animals and humans raises plasma IGF-1 and results in increases in skeletal muscle and lean body mass, a decrease in adiposity, increased immune function, improvements in learning and memory, and increases in cardiovascular function. Since growth hormone and IGF-1 exert potent effects on the heart and vasculature, the relationship between age-related changes in cardiovascular function and the decline in growth hormone levels with age have become of interest. Among the age-related changes in the cardiovascular system are decreases in myocyte number, accumulation of fibrosis and collagen, decreases in stress-induced cardiac function through deterioration of the myocardial conduction system and beta-adrenergic receptor function, decreases in exercise capacity, vessel rarefaction, decreased arterial compliance and endothelial dysfunction leading to alterations in blood flow. Growth hormone has been found to exert potent effects on cardiovascular function in young animals and reverses many of the deficits in cardiovascular function in aged animals and humans. Nevertheless, it has been difficult to separate the effects of growth hormone deficiency from age-related diseases and associated pathologies. The development of novel animal models and additional research are required in order to elucidate the specific effects of growth hormone deficiency and assess its

  6. Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HIV lipodystrophy syndrome (HLS) is characterized by accelerated lipolysis, inadequate fat oxidation, increased hepatic reesterification, and a high frequency of growth hormone deficiency (GHD). The effect of growth hormone (GH) replacement on these lipid kinetic abnormalities is unknown. We aimed ...

  7. Influence of prostaglandins and thyrotropin releasing hormone (TRH) on hormone secretion and growth in wether lambs.

    PubMed

    Davis, S L; Anfinson, M S; Klindt, J; Ohlson, D L

    1977-06-01

    A series of experiments were conducted in ewes and whether (castrate male) lambs to evaluate the influence of prostaglandins on secretion of anabolic hormones and to determine if repeated injections of prostaglandin (PG) F2alpha would chronically influence the secretion of these hormones and perhaps growth rate as well. A single intravenous injection of PGA1 and PGB1 (100 microgram/kg) exerted no significant (P greater than .10) influence on plasma concentrations of prolactin (PRL), growth hormone (GH) or thyrotropin (TSH) in ewes. PGA1, but not PGB1, stimulated an increase in the plasma concentration of insulin. Infusion of PGF2alpha for 5.5 hr into ewes resulted in increased (P less than .05) plasma concentrations of both GH and ARL while TSH and insulin were not significantly influenced. Prostaglandin F2alpha, when injected subcutaneously into wether lambs (10 mg twice weekly) stimulated (P less than .05) plasma GH concentrations after the first injection, but not after 3 weeks of treatment. Changes in plasma PRL or TSH were not observed consistently in the lambs treated chronically with PGF2alpha or TRH. Prostaglandin F2alpha, in the present studies, and PGE1 in previously reported studies (1-3), has been demonstrated to be stimulatory to the secretion of PRL and GH. In contrast, PGA1 and PGB1, which lack an 11-hydroxyl group, failed to influence the secretion of either PRL or GH. It would, therefore, appear that the 11-hydroxyl group is a structural requirement for prostaglandins to influence the secretion of these two hormones in sheep. Treatment with thyrotropin releasing hormone (TRH), alone or in combination with PGF 2alpha, significantly (P less than .05) increased growth rate (average daily gains) while PGF2alpha did not, despite the fact that both compounds exerted similar effects on plasma GH.

  8. Central administration of chicken growth hormone-releasing hormone decreases food intake in chicks.

    PubMed

    Tachibana, Tetsuya; Sugimoto, Ikue; Ogino, Madoka; Khan, Md Sakirul Islam; Masuda, Keiko; Ukena, Kazuyoshi; Wang, Yajun

    2015-02-01

    Growth hormone-releasing hormone (GHRH) is well known as a stimulator of growth hormone (GH) secretion. GHRH not only stimulates GH release but also modifies feeding behavior and energy homeostasis in rodents. In chickens (Gallus gallus domesticus), on the other hand, two types of GHRH, namely, chicken GHRH (cGHRH) and cGHRH-like peptide (cGHRH-LP), have been identified. The purpose of the present study was to investigate the effect of central injection of cGHRH and cGHRH-LP on feeding behavior in chicks. Intracerebroventricular (ICV) injection of both cGHRH and cGHRH-LP (0.04 to 1 nmol) significantly decreased food intake without any abnormal behavior in chicks. Furthermore, the feeding-inhibitory effect was not abolished by co-injection of the antagonist for pituitary adenylate cyclase-activating polypeptide (PACAP) or corticotropin-releasing hormone (CRH) receptors, suggesting that the anorexigenic effect of cGHRH and cGHRH-LP might not be related to the PACAP and CRH systems in the brain of chicks. Finally, 24-h food deprivation increased mRNA expression of cGHRH but not cGHRH-LP in the diencephalon. These results suggest that central cGHRH is related to inhibiting feeding behavior and energy homeostasis in chicks.

  9. Neither bST nor Growth Hormone Releasing Factor Alter Expression of Thyroid Hormone Receptors in Liver and Mammary Tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine, to specific nuclear receptors. It has been hypothesized that organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, target the action of thyroid hormones to the mammary...

  10. Introduction of exogenous growth hormone receptors augments growth hormone-responsive insulin biosynthesis in rat insulinoma cells

    SciTech Connect

    Billestrup, N.; Moeldrup, A.; Serup, P.; Nielsen, J.H. ); Mathews, L.S.; Norstedt, G. )

    1990-09-01

    The stimulation of insulin biosynthesis in the pancreatic insulinoma cell line RIN5-AH by growth hormone (GH) is initiated by GH binding to specific receptors. To determine whether the recently cloned rat hepatic GH receptor is able to mediate the insulinotropic effect of GH, the authors have transfected a GH receptor cDNA under the transcriptional control of the human metallothionein promoter into RIN5-AH cells. The transfected cells were found to exhibit an increased expression of GH receptors and to contain a specific GH receptor mRNA that was not expressed in the parent cell line. The expression of GH receptors in one clone (1.24) selected for detailed analysis was increased 2.6-fold compared to untransfected cells. The increased GH receptor expression was accompanied by an increased responsiveness to GH. Thus, the maximal GH-stimulated increase of insulin biosynthesis was 4.1-fold in 1.24 cells compared to 1.9-fold in the nontransfected RIN5-AH cells. The expression of the transfected receptor was stimulated 1.6- and 2.3-fold when cells were cultured in the presence of 25 or 50 {mu}M Zn{sup 2+} was associated with an increased magnitude of GH-stimulated insulin biosynthesis. A close stoichiometric relationship between the level of receptor expression and the level of GH-stimulated insulin biosynthesis was observed. They conclude from these results that the hepatic GH receptor is able to mediate the effect of GH on insulin biosynthesis in RIN5-AH cells.

  11. Hormonal growth promoting agents in food producing animals.

    PubMed

    Stephany, Rainer W

    2010-01-01

    In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone

  12. Growth Hormone Response to L-Dopa and Clonidine in Autistic Children.

    ERIC Educational Resources Information Center

    Realmuto, George M.; And Others

    1990-01-01

    Seven medication-free autistic subjects (ages 6-19) were administered clonidine and L-Dopa to investigate neuroendocrine responses through changes in growth hormone levels. Findings showed that, compared to normal controls, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. (Author/JDD)

  13. Role of 3', 5' cyclic adenosine monophosphate and protein kinase C in the regulation of insulin-like growth factor-binding protein secretion by thyroid-stimulating hormone in isolated ovine thyroid cells.

    PubMed

    Wang, J F; Hill, D J; Becks, G P

    1994-05-01

    Isolated sheep thyroid follicles release insulin-like growth factors (IGF)-I and -II together with IGF-binding proteins (IGFBPs). We previously showed that TSH suppresses the biosynthesis and release of IGFBPs in vitro which may increase the tissue availability of IGFs, allowing a synergy with TSH which potentiates both thyroid growth and function. Many of the actions of TSH on thyroid cell function are dependent upon activation of adenylate cyclase, although increased synthesis of inositol trisphosphate and activation of protein kinase C (PKC) have also been implicated. We have now examined whether probable changes in intracellular cyclic adenosine monophosphate (cAMP) or PKC are involved in TSH-mediated suppression of IGFBP release. Confluent primary cultures of ovine thyroid cells were maintained in serum-free Ham's modified F-12M medium containing transferrin, somatostatin and glycyl-histidyl-lysine (designated 3H), and further supplemented with sodium iodide (10(-8)-10(-3) mol/l), dibutyryl cAMP (0.25-1 mmol/l), forskolin (5-20 mumol/l) or 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-11)-10(-6) mol/l), with or without exposure to TSH (200 microU/ml). The uptake and organification of Na [125I] by cells was examined after test incubations of up to 48 h, and IGFBPs in conditioned media were analysed by ligand blot using 125I-labelled IGF-II. The PKC activity in the cytosol and plasma membrane fractions of cells was measured by phosphorylation of histone using [gamma-32P]ATP, and PKC immunoreactivity was visualized by Western immunoblot analysis. While dibutyryl cAMP or forskolin largely reproduced the stimulatory effect of TSH on iodine organification, they did not mimic the inhibitory effect of TSH on the secretion of IGFBPs of 43, 34, 28 and 19 kDa. Incubation with physiological or pharmacological concentrations of iodide (10(-6)-10(-3) mol/l) for up to 48 h significantly decreased TSH action on iodide uptake and organification but did not alter the

  14. Role of insulin-like growth factor monitoring in optimizing growth hormone therapy.

    PubMed

    Wetterau, L; Cohen, P

    2000-01-01

    Much has been learned over the past two decades regarding the management of growth hormone (GH) deficiency in children and adolescents. Current GH therapy under ideal circumstances enables children to attain a final height within the normal range and close to their target height. However, such a successful outcome is not always achieved and the necessity to individualize treatment according to the specific needs of each GH-deficient child is now well recognized. Consensus does not currently exist as to how to formulate individualized treatment plans. Nonetheless, a clear role for a biochemical, as well as an auxological, monitoring approach has been established. Accurate determinations of height velocity and interval height increase (expressed as the change in height Z-score) continue to be the most important parameters in monitoring the response to treatment. The importance of routinely monitoring serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is an emerging paradigm. Firm roles have been established for this approach in the assurance of compliance and safety (particularly to avoid long-term theoretical risks). IGF monitoring also has important potential utility as a tool to assess and optimize the response to GH therapy through dose adjustments. In years to come, we expect the development of multiple GH treatment optimization strategies, including approaches such as prediction modeling, as well as serum IGF monitoring and dose adjustments, to evolve and improve. PMID:11202212

  15. Recombinant DNA products: Insulin, interferon and growth hormone

    SciTech Connect

    Bollon, A.P.

    1984-01-01

    This book provides the discussion of products of biotechnology of recombinant DNA. The contents include: Recombinant DNA techniques; isolation, cloning, and expression of genes; from somatostatin to human insulin; yeast; an alternative organism for foreign protein production; background in human interferon; preclinical assessment of biological properties of recombinant DNA derived human interferons; human clinical trials of bacteria-derived human ..cap alpha.. interferon.f large scale production of human alpha interferon from bacteria; direct expression of human growth hormone in escherichia coli with the lipoprotein promoter; biological actions in humans of recombinant DNA synthesized human growth hormone; NIH guidelines for research involving recombinant DNA molecules; appendix; viral vectors and the NHY guidelines; FDA's role in approval and regulation of recombinant DNA drugs; and index.

  16. Allosteric modulation of hormone release from thyroxine and corticosteroid-binding globulins.

    PubMed

    Qi, Xiaoqiang; Loiseau, François; Chan, Wee Lee; Yan, Yahui; Wei, Zhenquan; Milroy, Lech-Gustav; Myers, Rebecca M; Ley, Steven V; Read, Randy J; Carrell, Robin W; Zhou, Aiwu

    2011-05-01

    The release of hormones from thyroxine-binding globulin (TBG) and corticosteroid-binding globulin (CBG) is regulated by movement of the reactive center loop in and out of the β-sheet A of the molecule. To investigate how these changes are transmitted to the hormone-binding site, we developed a sensitive assay using a synthesized thyroxine fluorophore and solved the crystal structures of reactive loop cleaved TBG together with its complexes with thyroxine, the thyroxine fluorophores, furosemide, and mefenamic acid. Cleavage of the reactive loop results in its complete insertion into the β-sheet A and a substantial but incomplete decrease in binding affinity in both TBG and CBG. We show here that the direct interaction between residue Thr(342) of the reactive loop and Tyr(241) of the hormone binding site contributes to thyroxine binding and release following reactive loop insertion. However, a much larger effect occurs allosterically due to stretching of the connecting loop to the top of the D helix (hD), as confirmed in TBG with shortening of the loop by three residues, making it insensitive to the S-to-R transition. The transmission of the changes in the hD loop to the binding pocket is seen to involve coherent movements in the s2/3B loop linked to the hD loop by Lys(243), which is, in turn, linked to the s4/5B loop, flanking the thyroxine-binding site, by Arg(378). Overall, the coordinated movements of the reactive loop, hD, and the hormone binding site allow the allosteric regulation of hormone release, as with the modulation demonstrated here in response to changes in temperature.

  17. [Acral acanthosis nigricans associated with taking growth hormone].

    PubMed

    Peña Irún, A

    2014-01-01

    Acanthosis nigricans is a skin lesion characterized by the presence of a hyperpigmented, velvety cutaneous thickening that usually appears in flexural areas. Less frequently, it can occur in other locations, such as the dorsum of hands and feet. In this case it is called acral acanthosis nigricans. It is a dermatological manifestation of systemic disease. It is often associated with insulin resistance-mediated endocrine diseases. A case is presented on a patient with acanthosis nigricans secondary to the use of growth hormone.

  18. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    SciTech Connect

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-08-01

    The specific binding of iodinated epidermal growth factor ((/sup 125/I)iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites (dissociation constant (Kd) = 0.7-1.8 nM). Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status.

  19. Regulation of skeletal muscle growth in fish by the growth hormone--insulin-like growth factor system.

    PubMed

    Fuentes, Eduardo N; Valdés, Juan Antonio; Molina, Alfredo; Björnsson, Björn Thrandur

    2013-10-01

    The growth hormone (GH)-insulin-like growth factor (IGF) system is the key promoter of growth in vertebrates; however, how this system modulates muscle mass in fish is just recently becoming elucidated. In fish, the GH induces muscle growth by modulating the expression of several genes belonging to the myostatin (MSTN), atrophy, GH, and IGF systems as well as myogenic regulatory factors (MRFs). The GH controls the expression of igf1 via Janus kinase 2 (JAK2)/signal transducers and activators of the transcription 5 (STAT5) signaling pathway, but it seems that it is not the major regulator. These mild effects of the GH on igf1 expression in fish muscle seem to be related with the presence of higher contents of truncated GH receptor1 (tGHR1) than full length GHR (flGHR1). IGFs in fish stimulate myogenic cell proliferation, differentiation, and protein synthesis through the MAPK/ERK and PI3K/AKT/TOR signaling pathways, concomitant with abolishing protein degradation and atrophy via the PI3K/AKT/FOXO signaling pathway. Besides these signaling pathways control the expression of several genes belonging to the atrophy and IGF systems. Particularly, IGFs and amino acid control the expression of igf1, thus, suggesting other of alternative signaling pathways regulating the transcription of this growth factor. The possible role of IGF binding proteins (IGFBPs) and the contribution of muscle-derived versus hepatic-produced IGF1 on fish muscle growth is also addressed. Thus, a comprehensive overview on the GH-IGF system regulating fish skeletal muscle growth is presented, as well as perspectives for future research in this field.

  20. Weight loss and wrestling training: effects on growth-related hormones.

    PubMed

    Roemmich, J N; Sinning, W E

    1997-06-01

    Adolescent wrestlers (n = 9, 15.4 yr) and recreationally active control males (n = 7, 15.7 yr) were measured before, at the end of, and 3.5-4 mo after a competitive wrestling season to assess the influence of dietary restriction on growth-related hormones. Wrestlers had significant elevations preseason to late season for morning serum concentrations (mean of 8 serial samples) of growth hormone (GH; 2.9 +/- 0.7 vs. 6.5 +/- 1.4 ng/ml) and sex hormone-binding globulin (SHBG; 16.1 +/- 2.3 vs. 27.9 +/- 6.9 nmol/l) and significant reductions in GH-binding protein (GHBP; 178 +/- 19 vs. 109 +/- 17 pmol/l), insulin-like growth factor I (IGF-I; 332 +/- 30 vs. 267 +/- 34 ng/ml), testosterone (T; 4.9 +/- 0.4 vs. 3.6 +/- 0.4 ng/ml), and free testosterone (Free-T; 22.4 +/- 3.6 vs. 15.7 +/- 2.8 pg/ml). Wrestlers had significant postseason reductions in GH (3.44 +/- 1.30 ng/ml) and SHBG (10.43 +/- 4.13 nmol/l) but elevations in GHBP (66.7 +/- 23.8 pmol/l), IGF-I (72.9 +/- 25.1 ng/ml), T (2.10 +/- 0.46 ng/ml), and Free-T (9.76 +/- 3.01 pg/ml). Concentrations of luteinizing hormone (LH), estradiol, prolactin, cortisol, insulin, and thyroid hormones did not differ because of exercise-dietary practices of wrestlers. In-season elevations in GH, with concomitant reductions in GHBP and IGF-I, that were reversed during the postseason suggest a reduction in GH receptor number and partial GH resistance during the season. Nonelevated LH with reduced T levels suggests a central hypothalamic-pituitary-gonadal (H-P-G) axis impairment. In conclusion, undernutrition may lead to altered H-P-G and GH-IGF-I axes function in adolescent wrestlers. However, only the wrestlers' late-season Free-T concentrations were outside the normal range, and the hormone axis impairments were quickly reversed. The present data do not address hormonal axis responses to several years of wrestling and weight loss.

  1. Insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I

    SciTech Connect

    Elgin, R.G.; Busby, H.W. Jr.; Clemmons, D.R.

    1987-05-01

    The insulin-like growth factors IGF-I and IGF-II circulate in blood bound to carrier proteins. The higher molecular mass IGF-binding protein complex (150 kDa) is composed of subunits, and one subunits that forms this complex is growth hormone dependent. In addition, many cell types and tissues secrete another form of IGF binding protein that is not growth hormone dependent. Both forms of the IGF binding protein are believed to inactivate the IGFs and to function as delivery systems to tissues. This conclusion was based on studies that determined the effects of impure preparations of these binding proteins or that examined the effect of these proteins only on the insulin-like actions of the IGFs. The authors report here that a pure preparation of the extracellular form of the IGF binding protein (purified from human amniotic fluid) markedly potentiated replication of several cell types in response to human IGF-I. Secondary cultures of human, mouse, and chicken embryo fibroblasts as well as porcine aortic smooth muscle cells showed marked enhancement of their DNA synthesis response to IGF-I in the presence of this protein. The binding protein not only potentiated the DNA synthesis response but also enhanced the increase in cell number in response to IGF-I. This stimulation is specific for growth factors that bind to the binding protein since incubation with insulin, which binds to the type I IGF receptor but not to the binding protein, did not result in potentiation of this response. They conclude that a form of IGF binding protein that is present in extracellular fluids and is secreted by many types of cells can markedly potentiate the cellular response to IGF-I.

  2. Serum Growth Hormone Levels and the Response of Diabetic Retinopathy to Pituitary Ablation*

    PubMed Central

    Wright, A. D.; Kohner, E. M.; Oakley, N. W.; Hartog, M.; Joplin, G. F.; Fraser, T. Russell

    1969-01-01

    Serum growth hormone levels were measured during insulin tolerance tests in 36 patients after yttrium-90 pituitary implantation for diabetic retinopathy. The response of the new blood vessels was more clearly related to loss of growth hormone function than was the improvement of retinal haemorrhages and microaneurysms. The overall response of the retinopathy was greatest when growth hormone function was lost. Since the loss of growth hormone function was related to the loss of other aspects of anterior pituitary function, a unique role of growth hormone in the response of diabetic retinopathy to pituitary ablation could not be established. PMID:5768460

  3. Longitudinal associations of age, anthropometric and lifestyle factors with serum total insulin-like growth factor-I and IGF binding protein-3 levels in Black and White men: the CARDIA Male Hormone Study.

    PubMed

    Gapstur, Susan M; Kopp, Peter; Chiu, Brian C-H; Gann, Peter H; Colangelo, Laura A; Liu, Kiang

    2004-12-01

    Although several studies have assessed cross-sectional correlates of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3), there are no longitudinal studies of the correlates of long-term changes in these measures. We examined the 8-year longitudinal associations of age, body mass index (BMI), waist circumference, physical activity, number of cigarettes smoked per day, and alcohol intake with serum total IGF-I and IGFBP-3 concentrations in 622 Black and 796 White male participants of the Coronary Artery Risk Development in Young Adults Study who were ages 20 to 34 years at the time of the first IGF measurement. In generalized estimating equation analyses, IGF-I decreased by 5.6 and 5.9 ng/mL per year increase in age for Black and White men, respectively (P< 0.0001), and there was an age-related decline in IGFBP-3 that was stronger in Whites (P < 0.0001) than Blacks (P = 0.21). Average IGF-I (beta = -17.51 ng/mL) and IGFBP-3 (beta = -355.4 ng/mL) levels across all three exams were lower in Blacks than Whites (P < 0.0001). Increased BMI was associated with decreased IGF-I (P < 0.0002), but was not associated with IGFBP-3. There were no meaningful associations with waist circumference. Increased physical activity was associated with a decrease in IGFBP-3 (P < 0.05), but was not associated with IGF-I. In White men, there were weak inverse associations between the number of cigarettes smoked per day with IGF-I (P=0.15) and with IGFBP-3 (P = 0.19), and in Black men, increased alcohol intake was associated with a decrease in IGF-I (P = 0.011). In conclusion, these results support an age-related decline and Black-White difference in serum IGF-I and IGFBP-3 levels. Importantly, they suggest that IGF-I and/or IGFBP-3 levels could be influenced by changes in BMI, and perhaps by physical activity, alcohol intake, and cigarette smoking.

  4. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

    PubMed Central

    Sun, Liou Y; Spong, Adam; Swindell, William R; Fang, Yimin; Hill, Cristal; Huber, Joshua A; Boehm, Jacob D; Westbrook, Reyhan; Salvatori, Roberto; Bartke, Andrzej

    2013-01-01

    We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity. DOI: http://dx.doi.org/10.7554/eLife.01098.001 PMID:24175087

  5. Hormones and the growth of plants in response to gravity.

    PubMed

    Osborne, D J

    1976-01-01

    Plants are remarkable amongst living things in that all their parts (leaves, stems, roots and flowers) can orientate their position in response to gravity. Roots normally grow downwards towards the stimulus, shoots upwards away from the stimulus, while leaves and special kinds of stems like underground rhizomes or aerial runners have adaptations to grow horizontally, approximately at right angles to the gravitational field. This directional positioning of the organ in relation to gravity is achieved by a regulation of the growth of enlarging cells below the meristems or within the organ. Mature tissues in which further cell growth is precluded are therefore unable to reorientate if their position in the field is changed. Under conditions of zero gravity, roots and shoots continue to grow in opposite directions and the orientation of laterals with respect to the apex is essentially normal. This demonstrates the inherent polarity of plant cells and the internal correlative growth regulation that each organ exerts upon its neighbours. The perception of gravity, involving statoliths, membranes and "wound" ethylene, is discussed, together with the mechanisms by which the subsequent growth responses can be mediated by changes in endogenous hormones. Evidence for how such hormonal changes can lead to modifications of the rate, extent and reorientation of cell growth is reviewed for several geotropically responding systems.

  6. Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma.

    PubMed

    Munabi, Naikhoba C O; Tan, Qian Kun; Garzon, Maria C; Behr, Gerald G; Shawber, Carrie J; Wu, June K

    2015-01-01

    Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.

  7. Early growth and postprandial appetite regulatory hormone responses.

    PubMed

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M; Holst, Jens J; Leiviskä, Jaana; Eriksson, Johan G

    2013-11-14

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34-69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

  8. Growth hormone, prolactin and thyrotrophin responses to thyrotrophin-releasing hormone in diabetic patients.

    PubMed Central

    Harrower, A. D.

    1980-01-01

    Growth hormone (GH), prolactin (PRL) and thyrotrophin (TSH) responses to thyrotrophin-releasing hormone (TRH) were studied in 15 insulin-dependent diabetic patients. Basal plasma GH levels were raised above 5 mu./l in 6 patients and following the injection of TRH there was a significant rise in plasma GH levels in 9. The mean rise in plasma GH from basal to peak values was significant in the group as a whole (P < 0.01). Basal PRL and TSH levels were normal and rose normally in response to TRH. GH release may be qualitatively abnormal in some diabetics and any such loss of specificity of GH-releasing mechanisms would further contribute to the raised GH levels found in many diabetics which would be of importance if GH is a factor in the aetiology of diabetic microangiopathy. PMID:6777767

  9. Regulation of hypothalamic somatostatin and growth hormone releasing hormone mRNA levels by inhibin.

    PubMed

    Carro, E; Señarís, R M; Mallo, F; Diéguez, C

    1999-03-20

    Although it is well established that inhibin plays a major role in the regulation of the hypothalamic-pituitary-gonadal axis, its influence in the regulation of other neuroendocrine functions is still poorly understood. Recent results indicate that inhibin suppresses plasma GH levels, but its site of action is yet unknown. Therefore, in the present work we investigated the effects of inhibin on somatostatin and growth hormone releasing hormone (GHRH) mRNA levels in the hypothalamus by 'in situ' hybridization. We found that inhibin administration (4, 12 and 24 h, i.c.v.) led to an increase in somatostatin mRNA levels in the periventricular nucleus, and to a decrease in GHRH mRNA content in the arcuate nucleus of the hypothalamus. These findings indicate that inhibin regulates the hypothalamic levels of somatostatin and GHRH mRNA.

  10. Gibberellins - a multifaceted hormone in plant growth regulatory network.

    PubMed

    Gantait, Saikat; Sinniah, Uma Rani; Ali, Md Nasim; Sahu, Narayan Chandra

    2015-01-01

    Plants tend to acclimatize to unfavourable environs by integrating growth and development to environmentally activated signals. Phytohormones strongly regulate convergent developmental and stress adaptive procedures and synchronize cellular reaction to the exogenous and endogenous conditions within the adaptive signaling networks. Gibberellins (GA), a group of tetracyclic diterpenoids, being vital regulators of plant growth, are accountable for regulating several aspects of growth and development of higher plants. If the element of reproduction is considered as an absolute requisite then for a majority of the higher plants GA signaling is simply indispensable. Latest reports have revealed unique conflicting roles of GA and other phytohormones in amalgamating growth and development in plants through environmental signaling. Numerous physiological researches have detailed substantial crosstalk between GA and other hormones like abscisic acid, auxin, cytokinin, and jasmonic acid. In this review, a number of explanations and clarifications for this discrepancy are explored based on the crosstalk among GA and other phytohormones.

  11. Growth hormone and insulin-like growth factor I plasma levels in patients with hypophosphatemic rickets.

    PubMed

    Jasper, H; Cassinelli, H

    1993-01-01

    The cause of the growth retardation present in patients with hypophosphatemic rickets has not been totally elucidated. There has been a previous report of a growth hormone deficit in a group of these patients. To verify this abnormality we studied two groups of patients with hypophosphatemic rickets, one with (n = 6) and the other without (n = 7) treatment with calcitriol and oral phosphates. All patients in both groups showed a normal growth hormone response (> 10 micrograms/l) to standard stimulatory tests and normal IGF-I plasma levels. Mean IGF-I plasma levels were not significantly different (untreated 1.46 +/- 0.80 U/ml, treated 1.25 +/- 0.69 U/ml) and the mean logarithmic deviation of IGF-I plasma levels from both groups did not differ from normal. In summary, we found no abnormalities of the growth hormone-IGF-I axis in our patients with hypophosphatemic rickets.

  12. CORAL: prediction of binding affinity and efficacy of thyroid hormone receptor ligands.

    PubMed

    Toropova, A P; Toropov, A A; Benfenati, E

    2015-08-28

    Quantitative structure - activity relationships (QSARs) for binding affinity of thyroid hormone receptors based on attributes of molecular structure extracted from simplified molecular input-line entry systems (SMILES) are established using the CORAL software (http://www.insilico.eu/coral). The half maximal inhibitory concentration (IC50) is used as the measure of the binding affinity of thyroid hormone receptors. Molecular features which are statistically reliable promoters of increase and decrease for IC50 are suggested. The examples of modifications of molecular structure which lead to the increase or to the decrease of the endpoint are represented. PMID:26188619

  13. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors.

    PubMed

    Seol, W; Choi, H S; Moore, D D

    1996-05-31

    SHP is an orphan member of the nuclear hormone receptor superfamily that contains the dimerization and ligand-binding domain found in other family members but lacks the conserved DNA binding domain. In the yeast two-hybrid system, SHP interacted with several conventional and orphan members of the receptor superfamily, including retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67. SHP also interacted directly with these receptors in vitro. In mammalian cells, SHP specifically inhibited transactivation by the superfamily members with which it interacted. These results suggest that SHP functions as a negative regulator of receptor-dependent signaling pathways. PMID:8650544

  14. Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors.

    PubMed

    Schmiegelow, M; Lassen, S; Poulsen, H S; Feldt-Rasmussen, U; Schmiegelow, K; Hertz, H; Müller, J

    2000-01-01

    Children with brain tumors are at high risk of developing growth hormone deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary (HP) axis falls within the fields of irradiation. The biological effective dose (BED) of irradiation to the HP region was determined, since BED gives a means of expressing the biological effect of various irradiation treatment schedules in a uniform way. Hypothalamic versus pituitary damage as cause of GHD was distinguished in 62 patients by comparing the growth hormone (GH) peak response to an insulin tolerance test (ITT)/arginine stimulation test and the GH response to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5--79.0 mU/l) than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01--75.0 mU/l) (p = 0.017). Peak GH after a GHRH test was significantly inversely correlated to follow-up time (r(s) = -0.46, p < 0.0001) and to BED (R(s) = -0.28, p = 0.03), and both were found to be of significance in a multivariante regression analysis. We speculate that a significant number of patients developed hypothalamic radiation-induced damage to the GHRH secreting neurons, and secondary to this the pituitary gland developed decreased responsiveness to GHRH following CI in childhood.

  15. Acute handling disturbance modulates plasma insulin-like growth factor binding proteins in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of acute stressor exposure on proximal (growth hormone; GH) and distal (insulin-like growth factor-I; IGF-I and IGF-binding proteins) components of the somatotropic axis are poorly understood in finfish. We exposed rainbow trout (Oncorhynchus mykiss) to a 5-minute handling disturbance to...

  16. Detection of recombinant growth hormone by evanescent cascaded waveguide coupler on silica-on-silicon.

    PubMed

    Ozhikandathil, Jayan; Packirisamy, Muthukumaran

    2013-05-01

    An evanescent wave based biosensor is developed on the silica-on-silicon (SOS) with a cascaded waveguide coupler for the detection of recombinant growth hormone. So far, U -bends and tapered waveguides are demonstrated for increasing the penetration depth and enhancing sensitivity of the evanescent wave sensor. In this work, a monolithically integrated sensor platform containing a cascaded waveguide coupler with optical power splitters and combiners designed with S -bends and tapper waveguides is demonstrated for an enhanced detection of recombinant growth hormone. In the cascaded waveguide coupler, a large surface area to bind the antibody with increased penetration depth of evanescent wave to excite the tagged-rbST is obtained by splitting the waveguide into multiple paths using Y splitters designed with s -bends and subsequently combining them back to a single waveguide through tapered waveguide and combiners. Hence a highly sensitive fluoroimmunoassay sensor is realized. Using the 2D FDTD (Finite-difference time-domain method) simulation of waveguide with a point source in Rsoft FullWAVE, the fluorescence coupling efficiency of straight and bend section of waveguide is analyzed. The sensor is demonstrated for the detection of fluorescently-tagged recombinant growth hormone with the detection limit as low as 25 ng/ml.

  17. Plant hormone cross-talk: the pivot of root growth.

    PubMed

    Pacifici, Elena; Polverari, Laura; Sabatini, Sabrina

    2015-02-01

    Root indeterminate growth and its outstanding ability to produce new tissues continuously make this organ a highly dynamic structure able to respond promptly to external environmental stimuli. Developmental processes therefore need to be finely tuned, and hormonal cross-talk plays a pivotal role in the regulation of root growth. In contrast to what happens in animals, plant development is a post-embryonic process. A pool of stem cells, placed in a niche at the apex of the meristem, is a source of self-renewing cells that provides cells for tissue formation. During the first days post-germination, the meristem reaches its final size as a result of a balance between cell division and cell differentiation. A complex network of interactions between hormonal pathways co-ordinates such developmental inputs. In recent years, by means of molecular and computational approaches, many efforts have been made aiming to define the molecular components of these networks. In this review, we focus our attention on the molecular mechanisms at the basis of hormone cross-talk during root meristem size determination.

  18. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 3; Plasma Analysis Hormone Measurements

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.; Popova, I. A.; Grossman, E.; Rudolph, I.

    1994-01-01

    Plasma from space flight and tail suspended rats was analyzed for a number of constituents in order to evaluate their metabolic status and endocrine function. The data presented here cover plasma hormone measurements. Corticosterone, thyroxine, and testosterone were measured by radioimmunoassay. Prolactin and growth hormone were measured by double antibody immunoassays using hormones and antisera prepared in house. Data were evaluated by analysis of variance.

  19. Growth Hormone-Insulin-Like Growth Factor Axis, Thyroid Axis, Prolactin, and Exercise.

    PubMed

    Hackney, Anthony C; Davis, Hope C; Lane, Amy R

    2016-01-01

    This chapter addresses what is known about the endocrine system components growth hormone (GH)-insulin-like growth factor (IGF) axis, thyroid axis, and prolactin relative to exercise and exercise training. Each one of these hormone axes contributes to the maintenance of homeostasis in the body through impact on a multitude of physiological systems. The homeostatic disruption of exercise causes differing responses in each hormone axis. GH levels increase with sufficient stimulation, and IGFs are released in response to GH from the anterior pituitary providing multiple roles including anabolic properties. Changes in the thyroid hormones T3 and T4 vary greatly with exercise, from increases/decreases to no change in levels across different exercise types, intensities and durations. These ambiguous findings could be due to numerous confounding factors (e.g. nutrition status) within the research. Prolactin increases proportionally to the intensity of the exercise. The magnitude may be augmented with extended durations; conflicting findings have been reported with resistance training. While the responses to exercise vary, it appears there may be overall adaptive and regenerative impacts on the body into recovery by these hormones through immune and tissue inflammatory responses/mediations. Nonetheless, well-designed exercise research studies are still needed on each of these hormones, especially thyroid hormones and prolactin. PMID:27348437

  20. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis

    PubMed Central

    Laurent, Michaël R.; Hammond, Geoffrey L.; Blokland, Marco; Jardí, Ferran; Antonio, Leen; Dubois, Vanessa; Khalil, Rougin; Sterk, Saskia S.; Gielen, Evelien; Decallonne, Brigitte; Carmeliet, Geert; Kaufman, Jean-Marc; Fiers, Tom; Huhtaniemi, Ilpo T.; Vanderschueren, Dirk; Claessens, Frank

    2016-01-01

    Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology. PMID:27748448

  1. Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.

    PubMed

    Hong, Huixiao; Branham, William S; Ng, Hui Wen; Moland, Carrie L; Dial, Stacey L; Fang, Hong; Perkins, Roger; Sheehan, Daniel; Tong, Weida

    2015-02-01

    One endocrine disruption mechanism is through binding to nuclear receptors such as the androgen receptor (AR) and estrogen receptor (ER) in target cells. The concentration of a chemical in serum is important for its entry into the target cells to bind the receptors, which is regulated by the serum proteins. Human sex hormone-binding globulin (SHBG) is the major transport protein in serum that can bind androgens and estrogens and thus change a chemical's availability to enter the target cells. Sequestration of an androgen or estrogen in the serum can alter the chemical elicited AR- and ER-mediated responses. To better understand the chemical-induced endocrine activity, we developed a competitive binding assay using human pregnancy plasma and measured the binding to the human SHBG for 125 structurally diverse chemicals, most of which were known to bind AR and ER. Eighty seven chemicals were able to bind the human SHBG in the assay, whereas 38 chemicals were nonbinders. Binding data for human SHBG are compared with that for rat α-fetoprotein, ER and AR. Knowing the binding profiles between serum and nuclear receptors will improve assessment of a chemical's potential for endocrine disruption. The SHBG binding data reported here represent the largest data set of structurally diverse chemicals tested for human SHBG binding. Utilization of the SHBG binding data with AR and ER binding data could enable better evaluation of endocrine disrupting potential of chemicals through AR- and ER-mediated responses since sequestration in serum could be considered.

  2. Growth Hormone-Releasing Hormone and Its Analogues: Significance for MSCs-Mediated Angiogenesis

    PubMed Central

    Tao, Quanwei; Ma, Qunchao; Chen, Huiqiang; Wang, Jian'an

    2016-01-01

    Mesenchymal stromal cells (MSCs) are promising candidates for regenerative medicine because of their multipotency, immune-privilege, and paracrine properties including the potential to promote angiogenesis. Accumulating evidence suggests that the inherent properties of cytoprotection and tissue repair by native MSCs can be enhanced by various preconditioning stimuli implemented prior to cell transplantation. Growth hormone-releasing hormone (GHRH), a stimulator in extrahypothalamus systems including tumors, has attracted great attentions in recent years because GHRH and its agonists could promote angiogenesis in various tissues. GHRH and its agonists are proangiogenic in responsive tissues including tumors, and GHRH antagonists have been tested as antitumor agents through their ability to suppress angiogenesis and cell growth. GHRH-R is expressed by MSCs and evolving work from our laboratory indicates that treatment of MSCs with GHRH agonists prior to cell transplantation markedly enhanced the angiogenic potential and tissue reparative properties of MSCs through a STAT3 signaling pathway. In this review we summarized the possible effects of GHRH analogues on cell growth and development, as well as on the proangiogenic properties of MSCs. We also discussed the relationship between GHRH analogues and MSC-mediated angiogenesis. The analyses provide new insights into molecular pathways of MSCs-based therapies and their augmentation by GHRH analogues. PMID:27774107

  3. Association of Turner Syndrome and Growth Hormone Deficiency: A Review.

    PubMed

    Marques, Jorge Sales; Aires, Sónia

    2015-09-01

    Turner syndrome (TS) is an important cause of short stature in girls. Patients with TS most often do not have growth hormone deficiency (GHD). Testing GH secretion is not indicated despite the presence of short stature. In the last 20 years only three cases were reported with this association in Pubmed. We describe a case of an 11 year old girl with short stature and karyotype confirmed TS: 45,X(16)46,X,i(X)(ql0)(13). Because her growth velocity was low (-3 SD), we evaluated the GH response with stimulating tests and the results were under the normal range. These findings were compatible with GHD. It is important to check for GHD in patients with TS whenever the growth velocity is low for age and sex.

  4. High specific activity enantiomerically enriched juvenile hormones: synthesis and binding assay

    SciTech Connect

    Prestwich, G.D.; Wawrzenczyk, C.

    1985-08-01

    A stereoselective total synthesis of chiral juvenile hormone I is described that allows stoichiometric introduction of two tritium atoms in the final step. Both optical antipodes of the pivotal epoxy alcohol intermediate were prepared in 95% enantiomeric excess by the Sharpless epoxidation of a (Z)-allylic alcohol. Elaboration of the hydroxy-methyl group to a vinyl group followed by selective homogeneous tritiation affords optically active juvenile hormone I analogs at 58 Ci/mmol. Competitive binding of the labeled 10R, 11S and 10S,11R enantiomers with unlabeled enantiomers to the hemolymph binding protein of Manduca sexta larvae was determined by using a dextran-coated charcoal assay. The natural 10R,11S enantiomer has twice the relative binding affinity of the 10S,11R enantiomer. The availability of such high specific activity optically pure hormones will contribute substantially to the search for high-affinity receptors for juvenile hormones in the nuclei of cells. Moreover, the chiral 12-hydroxy-(10R,11S)-epoxy intermediate allows modification of juvenile hormone for solid-phase biochemical and radioimmunochemical work without altering either the biologically important carbomethoxy or epoxy recognition sites.

  5. High specific activity enantiomerically enriched juvenile hormones: synthesis and binding assay.

    PubMed Central

    Prestwich, G D; Wawrzeńczyk, C

    1985-01-01

    A stereoselective total synthesis of chiral juvenile hormone I is described that allows stoichiometric introduction of two tritium atoms in the final step. Both optical antipodes of the pivotal epoxy alcohol intermediate were prepared in 95% enantiomeric excess by the Sharpless epoxidation of a (Z)-allylic alcohol. Elaboration of the hydroxy-methyl group to a vinyl group followed by selective homogeneous tritiation affords optically active juvenile hormone I analogs at 58 Ci/mmol. Competitive binding of the labeled 10R, 11S and 10S,11R enantiomers with unlabeled enantiomers to the hemolymph binding protein of Manduca sexta larvae was determined by using a dextran-coated charcoal assay. The natural 10R,11S enantiomer has twice the relative binding affinity of the 10S,11R enantiomer. The availability of such high specific activity optically pure hormones will contribute substantially to the search for high-affinity receptors for juvenile hormones in the nuclei of cells. Moreover, the chiral 12-hydroxy-(10R,11S)-epoxy intermediate allows modification of juvenile hormone for solid-phase biochemical and radioimmunochemical work without altering either the biologically important carbomethoxy or epoxy recognition sites. PMID:3860862

  6. Thyroid hormone mediates otolith growth and development during flatfish metamorphosis.

    PubMed

    Schreiber, A M; Wang, X; Tan, Y; Sievers, Q; Sievers, B; Lee, M; Burrall, K

    2010-11-01

    Flatfish begin life as bilaterally symmetrical larvae that swim up-right, then abruptly metamorphose into asymmetrically shaped juveniles with lateralized swimming postures. Flatfish metamorphosis is mediated entirely by thyroid hormone (TH). Changes in flatfish swim posture are thought to be regulated via vestibular remodeling, although the influence of TH on teleost inner ear development remains unclear. This study addresses the role of TH on the development of the three otolith end-organs (sacculus, utricle, and lagena) during southern flounder (Paralichthys lethostigma) metamorphosis. Compared with pre-metamorphosis, growth rates of the sacculus and utricle otoliths increase dramatically during metamorphosis in a manner that is uncoupled from general somatic growth. Treatment of P. lethostigma larvae with methimazol (a pharmacological inhibitor of endogenous TH production) inhibits growth of the sacculus and utricle, whereas treatment with TH dramatically accelerates their growth. In contrast with the sacculus and utricle otoliths that begin to form and mineralize during embryogenesis, a non-mineralized lagena otolith is first visible 10-12 days after hatching. The lagena grows during pre- and pro-metamorphosis, then abruptly mineralizes during metamorphic climax. Mineralization of the lagena, but not growth, can be induced with TH treatment, whereas treatment with methimazol completely inhibits lagena mineralization without inhibiting its growth. These findings suggest that during southern flounder metamorphosis TH exerts differential effects on growth and development among the three types of otolith.

  7. Recombinant growth hormone treatment of amyotrophic lateral sclerosis.

    PubMed

    Smith, R A; Melmed, S; Sherman, B; Frane, J; Munsat, T L; Festoff, B W

    1993-06-01

    Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced. PMID:8502260

  8. Lead (Pb) attenuation of plasma growth hormone output

    SciTech Connect

    Berry, W.D.; Moriarty, C.M.; Lau, Y.S.; Edwards, G.L.

    1996-03-08

    Lead (Pb) induced growth retardation may occur through disruption of the hypothalamic-pituitary-growth hormone (GH) axis. Episodic GH secretion and GH response to exogenous growth hormone releasing hormone (GHRH) were measured in rats chronically exposed to Pb. Male rats received lead nitrate (1000 ppm) in their drinking water from 21 through 49 days of age gained less weight than non-Pb treated controls (242{plus_minus}3 g vs 309{plus_minus}8 g, P{le}0.01). Mean blood Pb was 40 {plus_minus} 5 ug/dl in Pb treated rats vs. nondetectable in controls. Total food intake was increased by Pb treatment (340 vs 260 g/rat). Mean plasma GH levels were significantly reduced by Pb treatment (40.21 {plus_minus} 7 vs 71.53 {plus_minus} 11 ng/mlP= 0.025). However, the temporal pattern of episodic GH release was maintained in the Pb-treated rats. This indicates that Pb does not disrupt the timing of GHRH and somatostatin (SS) release from the hypothalamus but may alter the relative levels of GHRH and SS released. Pb treated rats also retained the ability to secrete GH in response to exogenous GHRH. However, response to GHRH tended to be lower in the Pb treated rats. The greatest effect of Pb was seen at the highest dose of GHRH 5 {mu}g/kg GHRH dose (485.6 {plus_minus} 103 vs. 870.2 {plus_minus} 317 ng/ml; P =0.2). This suggests that Pb disrupts GH synthesis, signal transduction, or secretory mechanisms in the somatotrope.

  9. Impact of growth hormone resistance on female reproductive function: new insights from growth hormone receptor knockout mice.

    PubMed

    Zaczek, Denise; Hammond, James; Suen, Lii; Wandji, Serge; Service, Darlene; Bartke, Andrzej; Chandrashekar, Varadaraj; Coschigano, Karen; Kopchick, John

    2002-10-01

    We examined multiple aspects of reproductive function in growth hormone receptor gene knockout (GHR-KO) and normal mice to clarify the role of growth hormone in female reproduction. In adult animals, estrous cycle duration was comparable in all mice housed individually but was significantly longer in group-housed GHR-KO females. Histological evaluation of ovaries of adult females at estrus showed that the numbers of preovulatory follicles and corpora lutea were significantly reduced in GHR-KO mice, as was the plasma estradiol level. The number of atretic preovulatory follicles was reduced in GHR gene-ablated animals. Although reverse transcription polymerase chain reaction analysis revealed reduced ovarian insulin-like growth factor I (IGF-I) mRNA expression in GHR-KO females, the expression of several steroidogenic enzyme mRNAs did not differ between groups. The numbers of active corpora lutea and uterine implantation sites were reduced in GHR-KO females at Day 7 of gestation. When young females were mated to normal males, latency to first mating and age of the female at first mating were significantly delayed in GHR-KO females, but maternal age at first conception was similar between groups. Significantly fewer virgin GHR-KO females exhibited pseudopregnancies when initially placed with vasectomized normal males than did normal female counterparts. Growth hormone resistance and IGF-I insufficiency negatively impacted 1) follicular development/ovulation rate, 2) sexual maturation, 3) production of and responsiveness to pheromonal signals, and 4) the ability of virgin females to respond to coitus by activation of luteal function. Although GHR-KO female mice are fertile, they exhibit quantitative deficits in various parameters of reproductive function.

  10. [Growth hormone administered to non-growth hormone deficient, small girls: echographic aspect of the gonads and uterus].

    PubMed

    Colle, M; Broussin, B

    1993-09-01

    The effect of growth hormone (GH) treatment on prepubertal gonads is controversial especially with regard to the risk of precocious puberty. Ultrasound assessment of ovarian volume, follicle size, and uterine growth was performed in 20 premenarcheal girls (8.0 +/- 2.6 years) receiving growth hormone (GH) for short stature (-2.8 +/- 0.4 SD) not related to growth hormone deficiency or Turner syndrome. Mean GH dosage was 1.0 +/- 0.4 IU/kg/week and mean duration of treatment at evaluation was 16.3 +/- 8.9 months. All patients underwent real time ultrasonography of the pelvic organs and ten subjects also had color Doppler studies of the ovarian and uterine arteries. Ultrasound findings were similar to those reported in normal prepubertal girls. Mean uterine length (29.1 +/- 7.5 mm) and volume (1.23 +/- 0.86 ml) were correlated with age but not with dosage or duration of GH treatment. Ovarian volumes was within the normal age-specific range in all patients except a 7.9 year old girl with substantially enlarged ovaries (4.7 ml) but no evidence or precocious puberty. Ovarian follicles were found in five girls; they measured less than 9 mm in diameter in every case except one (13 mm follicle in an 11-year-old). Blood flow in the ovarian arteries was seen on 5 of the 10 color Doppler studies and was not correlated with dosage or duration of GH treatment. Administration of GH to non-GH-deficient girls did not substantially affect the internal genital organs. It remains uncertain whether the single case of ovarian enlargement seen was related to GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice.

    PubMed

    Bartke, A; Cecim, M; Tang, K; Steger, R W; Chandrashekar, V; Turyn, D

    1994-09-01

    Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and

  12. Perspective: Proteomic approach to detect biomarkers of human growth hormone

    PubMed Central

    Ding, Juan; List, Edward O.; Okada, Shigeru; Kopchick, John J.

    2009-01-01

    Several serum biomarkers for recombinant human growth hormone (rhGH) have been established, however, none alone or in combination have generate a specific, sensitive, and reproducible ‘kit’ for the detection of rhGH abuse. Thus, the search for additional GH specific biomarkers continues. In this review, we focus on the use of proteomics in general and 2-dimensional electrophoresis (2-DE) in particular for the discovery of new GH induced serum biomarkers. Also, we review some of the protocols involved in 2DE. Finally, the possibility of tissues other than blood for biomarker discovery is discussed. PMID:19501004

  13. Human growth hormone: a case study in treatment priorities.

    PubMed

    Tauer, Carol A

    1995-01-01

    One of the most commonly cited examples of enhancement genetic engineering is insertion of the growth hormone (GH) gene into a medically normal child. At this time, insertion of the gene itself is not planned. However, the modification of height, which is possible through administration of biochemical GH, raises the same questions about therapeutic versus enhancement uses of genetics. While insertion of the gene is a more drastic measure and probably carries more risks, the question of appropriate limits on use of the GH drug raises similar ethical and policy questions.

  14. Algorithmic complexity of growth hormone release in humans.

    PubMed

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  15. Algorithmic complexity of growth hormone release in humans

    SciTech Connect

    Prank, K.; Wagner, M.; Brabant, G.

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  16. Glucocorticoids enhance stability of human growth hormone mRNA.

    PubMed Central

    Paek, I; Axel, R

    1987-01-01

    We have studied the control of expression of the human growth hormone (hGH) gene introduced into the chromosomes of mouse fibroblasts. Cell lines transformed with the hGH gene expressed low levels of intact hGH mRNA and secreted hGH protein into the medium. Although the level of expression of hGH mRNA was low, the gene remained responsive to induction by glucocorticoid hormones. To localize the sequences responsible for induction and to determine the mechanism by which these cis-acting sequences enhance gene expression, we have constructed a series of fusion genes between the hGH gene and the herpes simplex virus (HSV) thymidine kinase (tk) gene. We have demonstrated that a fusion gene in which hGH cDNA is flanked at its 5' terminus by an HSV tk promoter and is flanked at its 3' terminus by 3' HSV tk DNA remains inducible by glucocorticoids. Our studies indicate that the hGH exons contain sequences which are responsible for glucocorticoid hormone induction. Pulse-chase experiments, in vitro nuclear transcription, and approach to steady-state measurements indicate that the mechanisms responsible for induction of the hGH cDNA fusion gene operate posttranscriptionally to enhance the stability of hGH mRNA. Moreover, this increased stability was associated with an increase in the length of the 3' poly(A) tail on hGH mRNA. Images PMID:3037323

  17. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  18. Site-specific basicities regulate molecular recognition in receptor binding: in silico docking of thyroid hormones.

    PubMed

    Tóth, Gergő; Baska, Ferenc; Schretner, András; Rácz, Akos; Noszál, Béla

    2013-09-01

    Interactions between thyroid hormone α and β receptors and the eight protonation microspecies of each of the main thyroid hormones (thyroxine, liothyronine, and reverse liothyronine) were investigated and quantitated by molecular modeling. Flexible docking of the various protonation forms of thyroid hormones and high-affinity thyromimetics to the two thyroid receptors was carried out. In this method the role of the ionization state of each basic site could be studied in the composite process of molecular recognition. Our results quantitate at the molecular level how the ionization state and the charge distribution influence the protein binding. The anionic form of the carboxyl group (i.e., carboxylate site) is essential for protein binding, whereas the protonated form of amino group worsens the binding. The protonation state of the phenolate plays a less important role in the receptor affinity; its protonation, however, alters the electron density and the concomitant stacking propensity of the aromatic rings, resulting in a different binding score. The combined results of docking and microspeciation studies show that microspecies with the highest concentration at the pH of blood are not the strongest binding ones. The calculated binding free energy values can be well interpreted in terms of the interactions between the actual sites of the microspecies and the receptor amino acids. Our docking results were validated and compared with biological data from the literature. Since the thyroid hormone receptors influence several physiologic functions, such as metabolic rate, cholesterol and triglyceride levels, and heart frequency, our binding results provide a molecular basis for drug design and development in related therapeutic indications. PMID:23907234

  19. Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes

    PubMed Central

    Romero, Maritza J.; Lucas, Rudolf; Dou, Huijuan; Sridhar, Supriya; Czikora, Istvan; Mosieri, Eby M.; Rick, Ferenc G.; Block, Norman L.; Sridhar, Subbaramiah; Fulton, David; Weintraub, Neal L.; Bagi, Zsolt; Schally, Andrew V.

    2016-01-01

    Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. In a rat model of streptozotocin (STZ)-induced T1D, GHRH receptor expression was found to be up-regulated in the distal small intestine, a tissue involved in chylomicron synthesis. Treatment of T1D rats with a GHRH antagonist, MIA-602, at a dose that did not affect plasma GH levels, significantly reduced TRL, as well as markers of renal injury, and improved endothelial-dependent vasorelaxation. Glucagon-like peptide 1 (GLP-1) reduces hyperglucagonemia and postprandial TRL, the latter in part through a decreased synthesis of apolipoprotein B-48 (ApoB-48) by intestinal cells. Although plasma GLP-1 levels were elevated in diabetic animals, this was accompanied by increased rather than reduced glucagon levels, suggesting impaired GLP-1 signaling. Treatment with MIA-602 normalized GLP-1 and glucagon to control levels in T1D rats. MIA-602 also decreased secretion of ApoB-48 from rat intestinal epithelial cells in response to oleic acid stimulation in vitro, in part through a GLP-1–dependent mechanism. Our findings support the hypothesis that antagonizing the signaling of GHRH in T1D may improve GLP-1 function in the small intestine, which, in turn, diminishes TRL and reduces renal and vascular complications. PMID:26831066

  20. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling

    NASA Astrophysics Data System (ADS)

    Cheng, C.-Y.; Perevedentseva, E.; Tu, J.-S.; Chung, P.-H.; Cheng, C.-L.; Liu, K.-K.; Chao, J.-I.; Chen, P.-H.; Chang, C.-C.

    2007-04-01

    This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond's unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.

  1. Exercise and the growth hormone-insulin-like growth factor axis.

    PubMed

    Frystyk, Jan

    2010-01-01

    Exercise is a robust physiological stimulator of the pituitary secretion of growth hormone (GH), and within approximately 15 min after the onset of exercise, plasma GH starts to increase. GH and its primary downstream mediator, insulin-like growth factor I (IGF-I), play a critical role in formation, maintenance, and regeneration of skeletal muscles. Consequently, it seems logical to link the exercise-induced stimulation of GH with the hypertrophy observed in exercising muscles. GH stimulates circulating (endocrine) as well as locally produced (peripheral) IGF-I, which acts through autocrine/paracrine mechanisms. However, it remains to be clarified whether skeletal muscle hypertrophy after exercise is stimulated primarily by endocrine or paracrine/autocrine IGF-I. Early cross-sectional studies have observed positive correlations between circulating IGF-I levels and GH secretion, respectively, and indices of fitness. However, longitudinal exercise studies have shown that it is possible to increase muscle strength, performance, and VO2max without concomitant and robust changes in circulating IGF-I, indicating that the effect of exercise on skeletal muscles is mediated via paracrine/autocrine IGF-I rather than endocrine IGF-I. So far, most exercise studies have investigated the concentration of immunoreactive IGF-I in serum or plasma, obtained after extraction of the IGF-binding proteins (i.e., total IGF-I). However, several of the newer exercise studies have included measurement of free IGF-I as well as bioactive IGF-I. The aim of this review was to discuss whether measurement of free and/or bioactive IGF-I have increased our knowledge on the processes that link exercise, muscle hypertrophy, and GH/IGF-I axis. Thus, the current review will discuss (i) the different IGF-I assay methodologies and (ii) the current literature on free, bioactive, and immunoreactive (total) IGF-I in exercising subjects.

  2. Growth of functional cranial components in rats with intrauterine growth retardation after treatment with growth hormone.

    PubMed

    Quintero, Fabián Anibal; Castro, Luis Eduardo; Luna, María Eugenia; Guimarey, Luis Manuel; Cesani, María Florencia; Fucini, María Cecilia; Villanueva, Myriam; Prio, Verónica; Oyhenart, Evelia Edith

    2012-12-01

    The goal of this study was to analyse the effect of growth hormone (GH) on catch-up growth of functional facial (splanchnocranial) and neurocranial components in rats with intrauterine growth retardation (IUGR). Wistar rats were divided into the following groups: control (C), sham-operated (SH), IUGR, and IUGR + GH. IUGR was surgically induced and GH was administered between 21 and 60 days of age. Radiographs were obtained at 1, 21, 42, 63, and 84 days of age in order to measure length, width, and height of neurocranium (NL, NW, and NH) and face length, width, and height (FL, FW, and FH). Analysis of variance was performed at 1 day of age and a principal components analysis (PCA) at 84 days of age. Neurocranial and facial volumetric indexes were calculated as NVI = (3)√NL × NW × NH and FVI = (3)√FL × FW × FH, respectively, and adjusted by non-linear regression analysis. On postnatal day 1, there were significant differences between SH and IUGR (P < 0.01). Also, in both genders, final neurocranial volume was similar between SH and IUGR + GH groups, while the IUGR group had the lower value (P < 0.01). Final facial volume was similar among the three groups. In both genders, facial growth rates were SH = IUGR > IUGR + GH (P < 0.01). The first axis of the PCA exhibited size effect and the second axis showed shape effect. Reductions of placental blood flow modify cranial growth. The functional neurocranial and facial components in rats with IUGR presented different recovery strategies through modular behaviour, mainly related to modifications of growth rate as response to GH administration.

  3. Studies on the bioassayable growth hormone-like activity of plasma

    NASA Technical Reports Server (NTRS)

    Ellis, S.; Vodian, M. A.; Grindeland, R. E.

    1978-01-01

    Evidence supporting the existence of bioassayable growth hormone-like activity in blood plasma distinct from the growth hormone measurable by radioimmunoassay and from somatomedin is presented. Tibial assays of the growth-hormone-like activity of injected, concentrated normal human and rat plasma in hypophysectomized rats reveal 200- and 50-fold activity excesses, respectively, with respect to the amount of growth hormone detected by radioimmunoassay. The origin of this bioassayable plasma hormone has been localized to the region of the pituitary, the origin of growth hormone, a distribution not followed by somatomedin C. Purification of the bioassayable agent indicates that is has a molecular weight of between 60,000 and 80,000, in contrast to that of growth hormone (20,000), and that the bioassayable activity is distinct from that of somatomedin C. Growth hormone-like activity detected in Cohn fraction IV as well as plasma activity, are found to be collectable on Dowex 50 resin, in contrast to somatomedin C and nonsuppressible insulin-like activity. The formation of bioassayable growth hormone-activity agents from radioimmunoassayable growth hormone and directly in the pituitary is suggested.

  4. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  5. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  6. Effects of Plant Growth Hormones on Mucor indicus Growth and Chitosan and Ethanol Production.

    PubMed

    Safaei, Zahra; Karimi, Keikhosro; Golkar, Poorandokht; Zamani, Akram

    2015-01-01

    The objective of this study was to investigate the effects of indole-3-acetic acid (IAA) and kinetin (KIN) on Mucor indicus growth, cell wall composition, and ethanol production. A semi-synthetic medium, supplemented with 0-5 mg/L hormones, was used for the cultivations (at 32 °C for 48 h). By addition of 1 mg/L of each hormone, the biomass and ethanol yields were increased and decreased, respectively. At higher levels, however, an inverse trend was observed. The glucosamine fraction of the cell wall, as a representative for chitosan, followed similar but sharper changes, compared to the biomass. The highest level was 221% higher than that obtained without hormones. The sum of glucosamine and N-acetyl glucosamine (chitin and chitosan) was noticeably enhanced in the presence of the hormones. Increase of chitosan was accompanied by a decrease in the phosphate content, with the lowest phosphate (0.01 g/g cell wall) being obtained when the chitosan was at the maximum (0.45 g/g cell wall). In conclusion, IAA and KIN significantly enhanced the M. indicus growth and chitosan production, while at the same time decreasing the ethanol yield to some extent. This study shows that plant growth hormones have a high potential for the improvement of fungal chitosan production by M. indicus.

  7. Phylogenetic Investigation of Peptide Hormone and Growth Factor Receptors in Five Dipteran Genomes

    PubMed Central

    Vogel, Kevin J.; Brown, Mark R.; Strand, Michael R.

    2013-01-01

    Peptide hormones and growth factors bind to membrane receptors and regulate a myriad of processes in insects and other metazoans. The evolutionary relationships among characterized and uncharacterized (“orphan”) receptors can provide insights into receptor-ligand biology and narrow target choices in deorphanization studies. However, the large number and low sequence conservation of these receptors make evolutionary analysis difficult. Here, we characterized the G-protein-coupled receptors (GPCRs), receptor guanylyl cyclases (RGCs), and protein kinase receptors (PKRs) of mosquitoes and select other flies by interrogating the genomes of Aedes aegypti, Anopheles gambiae, Culex quinquefasciatus, Drosophila melanogaster, and D. mojavensis. Sequences were grouped by receptor type, clustered using the program CLANS, aligned using HMMR, and phylogenetic trees built using PhyML. Our results indicated that PKRs had relatively few orphan clades whereas GPCRs and RGCs had several. In addition, more than half of the Class B secretin-like GPCRs and RGCs remained uncharacterized. Additional studies revealed that Class B GPCRs exhibited more gain and loss events than other receptor types. Finally, using the neuropeptide F family of insect receptors and the neuropeptide Y family of vertebrate receptors, we also show that functional sites considered critical for ligand binding are conserved among distinct family members and between distantly related taxa. Overall, our results provide the first comprehensive analysis of peptide hormone and growth factor receptors for a major insect group. PMID:24379806

  8. Preparation and characterization of recombinant dolphin fish (Coryphaena hippurus) growth hormone.

    PubMed

    Paduel, A; Chapnik-Cohen, N; Gertler, A; Elizur, A

    1999-08-01

    Dolphin fish (Coryphaena hippurus) growth hormone (dfGH) cDNA encoding the mature protein was cloned in a pET11a expression vector and expressed in Escherichia coli BL21 cells upon induction with isopropyl-1-thio-beta-d-galactopyranoside as an insoluble protein. The expressed protein, contained within the inclusion-body pellet, was solubilized in 4.5 M urea, refolded at pH 11.3 in the presence of catalytic amounts of cysteine, and purified to homogeneity, as evidenced by SDS-PAGE. Gel filtration on a Superdex column under nondenaturing conditions and amino-terminal analysis showed the purified protein to be monomeric methionyl-dfGH. Binding assays of the (125)I-labeled dfGH to dolphin fish liver microsomal fraction resulted in high specific binding characterized by a K(a) of 0.77 nM(-1) and a B(max) of 285 fmol/mg microsomal fraction protein. The purified dfGH was capable of stimulating proliferation of FDC-P1-B9 cells transfected with rabbit growth hormone (GH) receptor. The maximal effect of dfGH was identical to that of human GH but their respective EC(50) values were 28 nM versus 0.095 nM. PMID:10425163

  9. Age- and sex-associated plasma proteomic changes in growth hormone receptor gene-disrupted mice.

    PubMed

    Ding, Juan; Berryman, Darlene E; Jara, Adam; Kopchick, John J

    2012-08-01

    Growth hormone receptor gene-disrupted (GHR-/-) mice are dwarf, insulin sensitive, and long lived despite being obese. In order to identify characteristics associated with their increased longevity, we studied age-related plasma proteomic changes in these mice. Male and female GHR-/- mice and their littermate controls were followed longitudinally at 8, 16, and 24 months of ages for plasma proteomic analysis. Relative to control littermates, GHR-/- mice had increased levels of apolipoprotein A-4 and retinol-binding protein-4 and decreased levels of apolipoprotein E, haptoglobin, and mannose-binding protein-C. Female GHR-/- mice showed decreased inflammatory cytokines including interleukin-1β and monocyte chemotactic protein-1. Additionally, sex differences were found in specific isoforms of apolipoprotein E, RBP-4, haptoglobin, albumin, and hemoglobin subunit beta. In conclusion, we find plasma proteomic changes in GHR-/- mice that favor a longer life span as well as sex differences indicative of an improved health span in female mice. PMID:22156438

  10. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    SciTech Connect

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Danielsen, Mark . E-mail: dan@bc.georgetown.edu

    2005-08-15

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids.

  11. Growth-hormone-releasing factor immunoreactivity in human endocrine tumors.

    PubMed Central

    Bostwick, D. G.; Quan, R.; Hoffman, A. R.; Webber, R. J.; Chang, J. K.; Bensch, K. G.

    1984-01-01

    Seventy-three human tumors and adjacent nonneoplastic tissues were analyzed immunohistochemically for the presence of growth-hormone-releasing factor (GRF). Four of 9 pancreatic endocrine tumors, 2 of 3 appendiceal carcinoids, and 1 of 5 cecal carcinoids were immunoreactive for GRF. One of the GRF-containing pancreatic tumors was associated with acromegaly. Histologically, the growth patterns of these tumors were variable, and the distribution of immunoreactive cells was patchy and irregular. There were no normal cells that contained GRF. These results indicate that GRF production by human tumors is more common than previously thought, although clinical acromegaly may not be apparent in patients who harbor such neoplasms. Images Figure 1 PMID:6093542

  12. Extrapituitary growth hormone in the chicken reproductive system.

    PubMed

    Luna, Maricela; Martínez-Moreno, Carlos G; Ahumada-Solórzano, Marisela S; Harvey, Steve; Carranza, Martha; Arámburo, Carlos

    2014-07-01

    Increasing evidence shows that growth hormone (GH) expression is not limited to the pituitary, as it can be produced in many other tissues. It is known that growth hormone (GH) plays a role in the control of reproductive tract development. Acting as an endocrine, paracrine and/or autocrine regulator, GH influences proliferation, differentiation and function of reproductive tissues. In this review we substantiate the local expression of GH mRNA and GH protein, as well as the GH receptor (GHR) in both male and female reproductive tract, mainly in the chicken. Locally expressed GH was found to be heterogeneous, with a 17 kDa variant being predominant. GH secretagogues, such as GHRH and TRH co-localize with GH expression in the chicken testis and induce GH release. In the ovarian follicular granulosa cells, GH and GHR are co-expressed and stimulate progesterone production, which was neutralized by a specific GH antibody. Both testicular and follicular cells in primary cultures were able to synthesize and release GH to the culture medium. We also characterized GH and GH mRNA expression in the hen's oviduct and showed that it had 99.6% sequence identity with pituitary GH. Data suggest local reproductive GH may have important autocrine/paracrine effects.

  13. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action

    PubMed Central

    2016-01-01

    Biologically active steroids are transported in the blood by albumin, sex hormone-binding globulin (SHBG), and corticosteroid-binding globulin (CBG). These plasma proteins also regulate the non-protein-bound or ‘free’ fractions of circulating steroid hormones that are considered to be biologically active; as such, they can be viewed as the ‘primary gatekeepers of steroid action’. Albumin binds steroids with limited specificity and low affinity, but its high concentration in blood buffers major fluctuations in steroid concentrations and their free fractions. By contrast, SHBG and CBG play much more dynamic roles in controlling steroid access to target tissues and cells. They bind steroids with high (~nM) affinity and specificity, with SHBG binding androgens and estrogens and CBG binding glucocorticoids and progesterone. Both are glycoproteins that are structurally unrelated, and they function in different ways that extend beyond their transportation or buffering functions in the blood. Plasma SHBG and CBG production by the liver varies during development and different physiological or pathophysiological conditions, and abnormalities in the plasma levels of SHBG and CBG or their abilities to bind steroids are associated with a variety of pathologies. Understanding how the unique structures of SHBG and CBG determine their specialized functions, how changes in their plasma levels are controlled, and how they function outside the blood circulation provides insight into how they control the freedom of steroids to act in health and disease. PMID:27113851

  14. Radioimmunoassay of human growth hormone: technique and application to plasma, cerebrospinal fluid, and pituitary extracts

    PubMed Central

    Thomas, Frances J.; Lloyd, H. M.; Thomas, M. J.

    1972-01-01

    A radioimmunoassay for human growth hormone using activated charcoal is described and its precision, accuracy, and sensitivity are defined. Results are presented for growth hormone measurements in plasma obtained during hypoglycaemia induced with insulin in patients of short stature and during glucose tolerance tests in patients with acromegaly. The method was used to measure growth hormone concentrations in cerebrospinal fluid and in extracts of pituitary tumours. No growth hormone was detected in the cerebrospinal fluid of patients without acromegaly. In patients with acromegaly, the concentration of growth hormone in cerebrospinal fluid was measurable and was considerably elevated in one patient with extrasellar extension of a pituitary tumour. Extracts of chromophobe pituitary tumours contained very small concentrations of growth hormone. In extracts of pituitary tumours removed from acromegalic patients, concentrations fell either below or within the normal range. PMID:5086220

  15. Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

    PubMed Central

    Kumar, Amit; Baumann, Monika; Balbach, Jochen

    2016-01-01

    Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required. PMID:26932583

  16. A thermodynamic study on the interaction between magnesium ion and human growth hormone.

    PubMed

    Saboury, A A; Atri, M S; Sanati, M H; Moosavi-Movahedi, A A; Hakimelahi, G H; Sadeghi, M

    2006-02-01

    A thermodynamic study on the interaction between magnesium ion and human growth hormone (hGH) was studied at 27 degrees C in NaCl solution (50 mM) using different techniques. Two techniques of ionmetry using a Mg2+selective membrane electrode and isothermal titration calorimetry were applied to obtain the binding isotherm for hGHMg2+; results obtained by both techniques were found to be in good agreement. There is a set of three identical and noninteracting binding sites for magnesium ions. The intrinsic dissociation equilibrium constant and the molar enthalpy of binding are 46 microM and -17.7 kJ/mol, respectively. Temperature scanning UV-visible spectroscopy was applied to elucidate the effect of Mg2+ binding on the protein stability, and circular dichroism (CD) spectroscopy was used to show the structural change of hGH due to the metal ion interaction. Magnesium ion binding increased the protein thermal stability by increasing the alpha-helix content as well as decreasing both beta and random coil structures. However, the secondary structural change of the protein returns to its native form, including a small change in the tertiary structure, in high concentrations of magnesium ion.

  17. Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory.

    PubMed

    Thornton, P L; Ingram, R L; Sonntag, W E

    2000-02-01

    The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.

  18. ( sup 3 H)idazoxan binding to the ovine myometrium. Binding characteristics and changes due to steroid hormones

    SciTech Connect

    Vass-Lopez, A.; Garcia-Villar, R.; Lafontan, M.; Toutain, P.L. )

    1990-05-01

    (3H)idazoxan binding to myometrial membranes was investigated in four groups of ewes under different steroid hormone status: control, estradiol-treated and progesterone plus estradiol-treated ovariectomized ewes and pregnant ewes. (3H)idazoxan binding to myometrial membrane fractions was saturable, reversible, specific and of high affinity. The affinity did not vary significantly between the four groups of ewes (2.8 less than KD less than 4.7 nM). Maximal binding capacity varied significantly among groups: binding of (3H)idazoxan was lower in control ovariectomized ewes than in either estradiol or progestagen plus estrogen-treated ewes (maximal binding capacity, 73 +/- 11 fmol/mg of protein vs. 108 +/- 16 and 318 +/- 65, respectively). The highest (3H)idazoxan binding was measured in pregnant ewes (maximal binding capacity, 1302 +/- 256 fmol/mg of protein). Based on the saturation studies with accurate nonspecific binding definition (phentolamine vs. epinephrine), and on the relative order of potency for selected adrenergic drugs, it could be stated that the binding sites labeled by (3H)idazoxan in our study exhibited most of the alpha-2 adrenoceptor properties. Nevertheless, these alpha-2 adrenoceptors obviously differed from the standard alpha-2A-subtype based on Ki values obtained with yohimbine and prazosin in competition studies of (3H)idazoxan binding. The increase in the number of alpha-2 adrenoceptors under progesterone domination, and especially during gestation, supported the hypothesis that this adrenoceptor subtype could play a major role in the control of the motility pattern of the ovine pregnant uterus.

  19. The cardiovascular system in growth hormone excess and growth hormone deficiency.

    PubMed

    Lombardi, G; Di Somma, C; Grasso, L F S; Savanelli, M C; Colao, A; Pivonello, R

    2012-12-01

    The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular

  20. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    SciTech Connect

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

  1. Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome.

    PubMed

    Devriendt, K; Lemli, L; Craen, M; de Zegher, F

    1995-01-01

    We report on a girl with the kabuki makeup syndrome, including short stature, premature thelarche and partial growth hormone deficiency of hypothalamic origin, without stalk interruption. Treatment with recombinant human growth hormone resulted in an increase of annualized growth velocity from 3.6 to 11.2 cm. The kabuki makeup syndrome may be associated with hypothalamopituitary dysfunction.

  2. Diminished growth hormone secretion in blind males after L-dopa stimulation.

    PubMed

    Fatranská, M; Jurcovicová, J; Németh, S; Vigas, M

    1988-12-01

    Growth hormone secretion after L-dopa administration (1000 mg p.o.) was investigated in young adult normal and blind volunteers. The average increment of plasma growth hormone after L-dopa stimulation in the blind was below the criterion for a positive response (less than 5 ng ml-1). The control volunteers showed normal response. After L-dopa stimulation there was a significantly diminished growth hormone response in the young adult blind compared to control volunteers. PMID:3243205

  3. Growth hormone deficiency in 18q deletion syndrome

    SciTech Connect

    Ghidoni, P.D.; Cody, J.; Danney, J.

    1994-09-01

    The 18q- syndrome is one of the most common chromosomal deletion syndromes. Clinical characteristics are variable but may include: hypotonia, cleft palate, mental retardation and hearing impairment. Growth failure (GF) (<3% weight/height) is present in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 15 patients with 18q- syndrome. Of these 15 patients, 10 have growth failure (<3% weight/height); of the remaining 5, 3 had normal growth parameters and 2 had growth along the 5%. Twelve patients failed to produce adequate GH following standard stimulation testing. Of these 12 patients with inadequate GH production, 2 had normal growth (above 3%). Of the 15, only 1 has normal GH production and normal growth parameters. Bone age was obtained on 1 patient with both GH deficiency and GF, and revealed significant delays. GH levels in response to GH releasing factor were normal in 3 out of 4 patients. MRI studies of GH-deficient patients indicated normal midline structures. Myelination in the few studied GH-deficient patients appeared delayed. The gene for myelin basic protein (MBP) is known to be located on the terminal portion of the long arm of chromosome 18. Neither the gene for GH, GH releasing factor nor GH releasing factor receptor is on chromosome 18. These genes are located on chromosomes 17, chromosome 20 and chromosome 7, respectively. Findings to date suggest that GH deficiency is common in individuals with 18q- syndrome. The etiology of this finding is unknown. We postulate that a gene(s) on chromosome 18q is involved in GH expression.

  4. Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

    PubMed

    Ignacio, Daniele Leão; da S Silvestre, Diego H; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade; Carvalho, Denise P; Werneck-de-Castro, João Pedro

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

  5. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas

    PubMed Central

    Abedelmalek, Salma; Chtourou, Hamdi; Souissi, Nizar; Tabka, Zouhair

    2015-01-01

    The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes. In a randomised order, 11 male judokas (age: 20.45 ± 0.51; height: 1.71 ± 0.3 m; and body weight: 75.9 ± 3.1 kg) participate in this study during a period of weight maintenance (baseline) and after 7 days of caloric restriction (CR). All subjects performed the Special Judo Fitness Test (SJFT) during the two conditions. Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction (−5~6 MJ/day). Our results showed that CR resulted in significant decreases in body weight (P < 0.05) and performance (P < 0.05). However, heart rate and SJFT index (P < 0.05) increase significantly during CR in comparison to baseline. Moreover, exercise leads to a significant increase in testosterone, cortisol, growth hormone (GH), leukocytes, neutrophils, TNF-α, and IL-6, in both CR and baseline conditions. Compared to baseline, TNF-α and IL-6 were significantly higher during CR condition (P < 0.05). Additionally, CR leads to an increase in cortisol and GH (P < 0.05) and a decrease in testosterone concentrations (P < 0.05). PMID:26075039

  6. Elevation of serum creatine phosphokinase during growth hormone treatment in patients with multiple pituitary hormone deficiency.

    PubMed

    Momoi, T; Yamanaka, C; Tanaka, R; Yoshida, A; Okumura, M; Yamakura, S; Takasaki, Y; Sasaki, H; Kawai, M

    1995-11-01

    Serum creatinine phosphokinase (s-CPK) increased to more than 500 U/l in 5 out of 21 patients with growth hormone (GH) deficiency during the 2 years of treatment with biosynthetic GH. In three of these five patients, s-CPK had elevated gradually after the start of GH treatment and remained high in one patient except in the period when GH injection was interrupted, and gradually decreased in the other two patients during treatment. These three patients had complete GH deficiency associated with multiple pituitary hormone deficiency due to pituitary stalk transection. One of the remaining two patients had Noonan syndrome and his s-CPK levels before therapy were relatively high. The fifth patient was a baseball athlete and the elevation of s-CPK seemed to be attributable to the strenuous exercise. Conclusion. s-CPK increases significantly in a certain group of patients with GH deficiency during GH replacement therapy. Measurement of s-CPK is to be included in the follow up laboratory tests at least in the 1st treatment year to evaluate the potential hazardous effects of GH on muscle.

  7. Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

    PubMed Central

    Ignacio, Daniele Leão; da S. Silvestre, Diego H.; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

  8. Growth hormone-releasing hormone (GHRH) polymorphisms associated with carcass traits of meat in Korean cattle

    PubMed Central

    Cheong, Hyun Sub; Yoon, Du-Hak; Kim, Lyoung Hyo; Park, Byung Lae; Choi, Yoo Hyun; Chung, Eui Ryong; Cho, Yong Min; Park, Eng Woo; Cheong, Il-Cheong; Oh, Sung-Jong; Yi, Sung-Gon; Park, Taesung; Shin, Hyoung Doo

    2006-01-01

    Background Cold carcass weight (CW) and longissimus muscle area (EMA) are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH) gene and examined the association of polymorphisms with carcass traits (CW and EMA) in Korean native cattle (Hanwoo). Results By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428) and five marker haplotypes (frequency > 0.1) were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. Conclusion Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle. PMID:16749938

  9. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas.

    PubMed

    Abedelmalek, Salma; Chtourou, Hamdi; Souissi, Nizar; Tabka, Zouhair

    2015-01-01

    The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes. In a randomised order, 11 male judokas (age: 20.45 ± 0.51; height: 1.71 ± 0.3 m; and body weight: 75.9 ± 3.1 kg) participate in this study during a period of weight maintenance (baseline) and after 7 days of caloric restriction (CR). All subjects performed the Special Judo Fitness Test (SJFT) during the two conditions. Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction (-5~6 MJ/day). Our results showed that CR resulted in significant decreases in body weight (P < 0.05) and performance (P < 0.05). However, heart rate and SJFT index (P < 0.05) increase significantly during CR in comparison to baseline. Moreover, exercise leads to a significant increase in testosterone, cortisol, growth hormone (GH), leukocytes, neutrophils, TNF-α, and IL-6, in both CR and baseline conditions. Compared to baseline, TNF-α and IL-6 were significantly higher during CR condition (P < 0.05). Additionally, CR leads to an increase in cortisol and GH (P < 0.05) and a decrease in testosterone concentrations (P < 0.05).

  10. The Influence of a 12-Week Conditioning Program on Growth Hormone and Somatomedin C Concentrations in Moderately Overweight Males.

    ERIC Educational Resources Information Center

    Kinard, James D.; Bazzarre, Terry L.

    The growth hormone is a lipolytic hormone and somatomedin C mediates the metabolic effects of the growth hormone in many tissues. Growth hormone plasma levels are often depressed in obese individuals, and this low plasma level has been postulated as a reason for perpetuation of excess weight. Substantial weight loss in obese subjects improves…

  11. The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

    PubMed

    Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R

    2010-06-01

    Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

  12. Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy

    PubMed Central

    Christ, Emanuel R.; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

    2016-01-01

    Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50–60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn’t significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids. PMID:26792091

  13. Vascular remodeling in the growth hormone transgenic mouse.

    PubMed

    Dilley, R J; Schwartz, S M

    1989-11-01

    Using mice transgenic for the growth hormone gene (TGHM), we have studied the effects of a systemic elevation of growth hormone on vascular growth with the aim of investigating the role of vascular mass changes in producing hypertension. In contrast to human acromegaly or gigantism, there was no elevation of blood pressure in TGHM, but there were significant increases in vascular wall mass. In accordance with a presumably increased perfusion of larger organs, the medial cross-sectional areas of thoracic aorta and mesenteric resistance vessels were greater in the TGHM. These differences could be normalized in the aorta by body weight and in the mesenteric vessel by small intestine weight. Furthermore, the brain was not significantly heavier in the TGHM, and their carotid and cerebral vessels also were not larger. Wall-to-lumen ratios were similar in the aorta, carotid, and middle cerebral arteries suggesting that wall stress was the controlling factor in wall thickness. Surprisingly, the mesenteric vessels had increased wall-to-lumen ratio, which was similar to that seen in hypertensive vascular remodeling but in a normotensive animal. In an attempt to explain this finding it was noted that the pattern of mesenteric vascular networks and even organized structure within the vessel wall itself appeared to be fixed, perhaps by genetic mechanisms. Thus, vascular network structure may be a potentially limiting factor in the ability of the vessel wall to remodel and may have been responsible for the greater wall-to-lumen ratio in TGHM mesenteric vessels. A similar situation in human acromegaly or gigantism could result in a circulation marginally able to correct for other demands on blood flow resulting in about one third of cases being hypertensive. PMID:2805241

  14. Nutritional state modulates growth hormone-stimulated lipolysis.

    PubMed

    Bergan, Heather E; Kittilson, Jeffrey D; Sheridan, Mark A

    2015-01-01

    Growth hormone (GH) regulates several processes in vertebrates, including two metabolically disparate processes: promotion of growth, an anabolic action, and mobilization of stored lipid, a catabolic action. In this study, we used hepatocytes isolated from continuously fed and long-term (4weeks) fasted rainbow trout (Oncorhynchus mykiss) as a model to investigate the mechanistic basis of the anabolic and catabolic actions of GH. Our hypothesis was that nutritional state modulates the lipolytic responsiveness of cells by adjusting the signal transduction pathways to which GH links. GH stimulated lipolysis as measured by increased glycerol release in both a time- and concentration-related manner from cells of fasted fish but not from cells of fed fish. Expression of mRNAs that encode the lipolytic enzyme hormone-sensitive lipase (HSL), HSL1 and HSL2, also was stimulated by GH in cells from fasted fish and not in cells from fed fish. Activation of the signaling pathways that mediate GH action also was studied. In cells from fed fish, GH activated the JAK-STAT, PI3K-Akt, and ERK pathways, whereas in cells from fasted fish, GH activated the PLC/PKC and ERK pathways. In hepatocytes from fasted fish, blockade of PLC/PKC and of the ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated HSL mRNA expression, whereas blockade of JAK-STAT or of the PI3K-Akt pathway had no effect on lipolysis or HSL expression stimulated by GH. These results indicate that during fasting GH activates the PLC/PKC and ERK pathways resulting in lipolysis but during periods of feeding GH activates a different complement of signal elements that do not promote lipolysis. These findings suggest that the responsiveness of cells to GH depends on the signal pathways to which GH links and helps resolve the growth-promoting and lipid catabolic actions of GH.

  15. Juvenile hormone-binding proteins of Melanoplus bivittatus identified by EFDA photoaffinity labeling

    SciTech Connect

    Winder, B.S.

    1988-01-01

    Proteins that bind juvenile hormone in the hemolymph and fat body of the grasshopper, Melanoplus bivittatus were identified by photoaffinity labeling with radiolabeled epoxyfarnesyl diazoacetate ({sup 3}H-EFDA), and were characterized by electrophoretic analysis. A protocol was developed which allowed detection of {sup 3}H-EFDA that was covalently linked to proteins upon exposure to ultraviolet light at 254 nm. Quantification of protein-linked {sup 3}H-EFDA by liquid scintillation spectrometry took advantage of the differential solubility of unlinked {sup 3}H-EFDA in toluene alone, and of the protein-linked {sup 3}H-EFDA in toluene plus the detergent, Triton X-100. Competition between EFDA and juvenile hormone (JH) for binding to JH-specific binding sites was measured by hydroxyapatite protein binding assays in the presence of radiolabeled JH or EFDA and competing non-radiolabeled hormone. The protein-linked EFDA was detected on fluorograms of SDS or nondenaturing polyacrylamide gels (PAGE), and by liquid scintillation spectrometry of membranes to which the proteins had been electrophoretically transferred. Proteins which specifically bound JH were identified by photolabeling proteins in the presence and absence of nonlabeled JH-III.

  16. Hormonal regulation of temperature-induced growth in Arabidopsis.

    PubMed

    Stavang, Jon A; Gallego-Bartolomé, Javier; Gómez, María D; Yoshida, Shigeo; Asami, Tadao; Olsen, Jorunn E; García-Martínez, José L; Alabadí, David; Blázquez, Miguel A

    2009-11-01

    Successful plant survival depends upon the proper integration of information from the environment with endogenous cues to regulate growth and development. We have investigated the interplay between ambient temperature and hormone action during the regulation of hypocotyl elongation, and we have found that gibberellins (GAs) and auxin are quickly and independently recruited by temperature to modulate growth rate, whereas activity of brassinosteroids (BRs) seems to be required later on. Impairment of GA biosynthesis blocked the increased elongation caused at higher temperatures, but hypocotyls of pentuple DELLA knockout mutants still reduced their response to higher temperatures when BR synthesis or auxin polar transport were blocked. The expression of several key genes involved in the biosynthesis of GAs and auxin was regulated by temperature, which indirectly resulted in coherent variations in the levels of accumulation of nuclear GFP-RGA (repressor of GA1) and in the activity of the DR5 reporter. DNA microarray and genetic analyses allowed the identification of the transcription factor PIF4 (phytochrome-interacting factor 4) as a major target in the promotion of growth at higher temperature. These results suggest that temperature regulates hypocotyl growth by individually impinging on several elements of a pre-existing network of signaling pathways involving auxin, BRs, GAs, and PIF4.

  17. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    PubMed

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  18. Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats.

    PubMed

    Schneider-Rivas, S; Rivas-Arancibia, S; Vázquez-Pereyra, F; Vázquez-Sandoval, R; Borgonio-Pérez, G

    1995-01-01

    The purpose of this work is to study the participation of growth hormone (GH) and growth hormone releasing hormone (GHRH) in the modulation of long-term memory and the extinction response of a passive avoidance task in rats. However, the effect on memory vary according to the age of the animals due to plasma levels of either hormone being modified during the aging process. Male Wistar rats were divided according to age into two experimental blocks (young rats 3 months old and aged rats 24 months old at the start of the experiment) where each block received the same treatment. Each experimental block was then divided randomly into three groups where two were experimental and the other served as control. The animals were then submitted to a one-trial passive avoidance conditioning and tested for memory retention 24 hrs after as well as twice a week until the extinction response occurred. The control group received an isotonic saline solution and the other two groups received 0.8 U.I. of GH or 4 mcg of GHRH respectively. All substances were in a 0.08 ml volume and applied 24 hrs before training as well as 24 hrs before each retention session. The results indicate that GH and GHRH modulate long-term memory as well as the extinction response and in either case the response seems to vary with age. GH and GHRH facilitates long-term memory in young rats but not in aged rats. Finally, whereas GH delays the extinction response in both groups, GHRH retards the extinction only in aged rats.

  19. Ethanol, growth hormone and testosterone in peripubertal rats.

    PubMed

    Tentler, J J; LaPaglia, N; Steiner, J; Williams, D; Castelli, M; Kelley, M R; Emanuele, N V; Emanuele, M A

    1997-03-01

    The deleterious effects of ethanol on the hypothalamic pituitary growth hormone axis in adult male humans and animals have been well documented. It is also well established that ethanol has toxic effects on testicular function in adult humans and animals. Much less is known, however, about the effects of ethanol on the growth hormone (GH) axis and testicular function in adolescence. Recent studies have established that adolescent problem drinking is a widespread and growing threat to the health of young people in the United States. In the present study, therefore, we investigated if acute ethanol exposure in peripubertal male Sprague-Dawley rats altered normal pituitary and testicular function. Serum levels of GH and testosterone were measured at 1.5, 3, 6, and 24 h after a single i.p. injection of either saline or 3 g/kg body weight ethanol. Histologic analysis as well as serum testosterone levels allowed us to assign animals to either early puberty (35-day-old animals), mid-puberty (41-day-old animals), or young adult (51- and 66-day-old animals) status. Ethanol produced significant decrements in serum testosterone in the 51- and 66-day-old animals, with a trend toward suppression in the 41-day-old group. Furthermore acute ethanol administration significantly decreased serum GH (P < 0.0001 by 3 way ANOVA) demonstrating a significant effect of ethanol on serum GH in all age groups and at all time points studied when compared with saline injected controls (P < 0.01 by Turkey's studentized range test). Despite this significant fall in peripheral GH levels, there was no decrease in either GH mRNA or growth hormone-releasing factor (GRF) mRNA levels nor in hypothalamic concentration of GRF peptide. We conclude that, as in adult animals, acute exposure to ethanol causes a prolonged and severe decrement in serum GH which is possibly mediated at the level of secretion. In addition, there is attenuation in testosterone secretion. These data are all the more important

  20. USE OF MOLECULAR BIOLOGICAL TECHNIQUES TO EVALUATE EFFECT OF ENDOGENOUS HORMONES AND A XENOBIOTIC PESTICIDE ON GROWTH OF SHEEPSHEAD MINNOW

    EPA Science Inventory

    We have developed a teleost model to screen physiological effects of endocrine disrupting chemicals (EDCs) on somatic growth. Growth is largely controlled by the endocrine system via the growth-hormone releasing hormone (GRF) - growth hormone (GH) - insulin-like growth factor (IG...

  1. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates.

    PubMed

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C; Flores-Morales, A

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This crosstalk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  2. Pituitary function and growth hormone dynamics in acromegaloidism.

    PubMed

    Mims, R B

    1978-12-01

    Acromegaloidism is a condition which resembles acromegaly by its clinical manifestations but is not due to pituitary or hypothalamic dysfunction. Twenty patients were diagnosed as having this disorder and the results from studying growth hormone (GH) responses in 15 patients (11 women and four men) were included in this report. Clinical manifestations closely resembled those of acromegalics, including history of progressive changes, acral enlargement, visual disturbances, abnormal visual fields in four patients, and sella turcica enlargement in two patients. The glucose tolerance test (GTT) was abnormal in 12/15 patients, 13/15 were > 10 percent obese, 8/15 had hypertension, 7/15 had large-statured relatives, but lactorrhea was absent in all patients. The mean serum GH concentration was 2.2 ng/ml, which suppressed to 0.6 ng/ml during the GTT; increased to 24 ng/ml during hypoglycemia; and increased to 10.3 ng/ml after L-dopa ingestion. Other pituitary hormones (LH, FSH, TSH, prolactin), the metyrapone test, 24-hour random and nocturnal sleeping GH concentrations were normal. These GH values and responses helped to differentiate acromegaloidism from treated and untreated acromegaly. The pathogenesis of acromegaloidism was not determined, but somatomedin studies may prove helpful in further defining this disorder. PMID:731719

  3. Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas.

    PubMed

    Sarkar, C; Dinda, A K; Roy, S; Kochupillai, N; Kharbanda, K; Tandon, P N

    1992-08-01

    An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.

  4. Emerging options in growth hormone therapy: an update

    PubMed Central

    Kemp, Stephen F; Frindik, J Paul

    2011-01-01

    Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA) for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS), which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell–Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks. PMID:21966214

  5. McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

    PubMed

    Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

    2006-05-01

    McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS. PMID:16789626

  6. Effects of bovine fatty acid synthase, stearoyl-coenzyme A desaturase, sterol regulatory element-binding protein 1, and growth hormone gene polymorphisms on fatty acid composition and carcass traits in Japanese Black cattle.

    PubMed

    Matsuhashi, T; Maruyama, S; Uemoto, Y; Kobayashi, N; Mannen, H; Abe, T; Sakaguchi, S; Kobayashi, E

    2011-01-01

    The quality of fat is an important factor in defining the quality of meat. Fat quality is determined by the composition of fatty acids. Among lipid metabolism-related genes, including fatty acid synthesis genes, several genetic variations have been reported in the bovine fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), sterol regulatory element-binding protein 1 (SREBP1), and GH genes. In the present study, we evaluated the single and epistatic effects of 5 genetic variations (4 SNP and 1 insertion/deletion) in 4 genes (FASN, SCD, SREBP1, and GH) on the fatty acid composition of the longissimus thoracis muscle and carcass and meat quality traits in 480 commercial Japanese Black cattle. Significant single effects of FASN, SCD, and GH(L127V) polymorphisms on the fatty acid composition of the longissimus thoracis muscle were detected. The A293V polymorphism of SCD had the largest effect on myristic acid (C14:0, P < 0.001), myristoleic acid (C14:1, P < 0.001), stearic acid (C18:0, P < 0.001), oleic acid (C18:1, P < 0.001), and MUFA (P < 0.001). Polymorphisms in the FASN, SCD, and SREBP1 genes showed no effect on any meat yield trait. There were no significant epistatic effects on fatty acid composition among pairs of the 3 genes (FASN, SCD, and SREBP1) involved in fatty acid synthesis. No epistatic interactions (P > 0.1) were detected between FASN and SCD for any carcass trait. When the genotypes of 3 markers (FASN, SCD, and GH(L127V)) were substituted from the lesser effect allele to the greater effect allele, the proportion of C18:1 increased by 4.46%. More than 20% of the genetic variance in the C18:1 level could be accounted for by these 3 genetic markers. The present results revealed that polymorphisms in 2 fatty acid synthesis genes (FASN and SCD) independently influenced fatty acid composition in the longissimus thoracis muscle. These results suggest that SNP in the FASN and SCD genes are useful markers for the improvement of fatty acid composition in

  7. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    NASA Technical Reports Server (NTRS)

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  8. Intrauterine growth restriction perturbs nucleosome depletion at a growth hormone-responsive element in the mouse IGF-1 gene.

    PubMed

    McKnight, Robert A; Yost, Christian C; Yu, Xing; Wiedmeier, Julia E; Callaway, Christopher W; Brown, Ashley S; Lane, Robert H; Fung, Camille M

    2015-12-01

    Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sham-operated, and IUGR mice. Nucleosome occupancy and CpG methylation were determined in embryonic stem cells (ESCs) and in liver at postnatal days 14, 21, and 42. For CpG methylation, additional time points out to 2 yr were analyzed. We confirmed the putative mouse in2GHRE was GH-responsive, and in normal mice, a single nucleosome was displaced from the hepatic in2GHRE by postnatal day 21, which exposed two STAT5b DNA binding sites. Nucleosome displacement correlated with developmentally programmed CpG demethylation. Finally, IUGR significantly altered the nucleosome-depleted region (NDR) at the in2GHRE of IGF-1 on postnatal day 21, with either complete absence of the NDR or with a shifted NDR exposing only one of two STAT5b DNA binding sites. An NDR shift was also seen in offspring of sham-operated mothers. We conclude that prenatal insult such as IUGR or anesthesia/surgery could perturb the proper formation of a well-positioned NDR at the mouse hepatic IGF-1 in2GHRE necessary for transitioning to an open chromatin state.

  9. Intrauterine growth restriction perturbs nucleosome depletion at a growth hormone-responsive element in the mouse IGF-1 gene.

    PubMed

    McKnight, Robert A; Yost, Christian C; Yu, Xing; Wiedmeier, Julia E; Callaway, Christopher W; Brown, Ashley S; Lane, Robert H; Fung, Camille M

    2015-12-01

    Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sham-operated, and IUGR mice. Nucleosome occupancy and CpG methylation were determined in embryonic stem cells (ESCs) and in liver at postnatal days 14, 21, and 42. For CpG methylation, additional time points out to 2 yr were analyzed. We confirmed the putative mouse in2GHRE was GH-responsive, and in normal mice, a single nucleosome was displaced from the hepatic in2GHRE by postnatal day 21, which exposed two STAT5b DNA binding sites. Nucleosome displacement correlated with developmentally programmed CpG demethylation. Finally, IUGR significantly altered the nucleosome-depleted region (NDR) at the in2GHRE of IGF-1 on postnatal day 21, with either complete absence of the NDR or with a shifted NDR exposing only one of two STAT5b DNA binding sites. An NDR shift was also seen in offspring of sham-operated mothers. We conclude that prenatal insult such as IUGR or anesthesia/surgery could perturb the proper formation of a well-positioned NDR at the mouse hepatic IGF-1 in2GHRE necessary for transitioning to an open chromatin state. PMID:26487705

  10. AIDS activists secure approval for human growth hormone (Serostim).

    PubMed

    1996-01-01

    The Food and Drug Administration (FDA) has given a verbal commitment to accelerated approval for recombinant human growth hormone (Serostim) for AIDS-associated wasting syndrome. The drug, manufactured by Serono Laboratories, is the first of its kind that directly affects the metabolic dysfunction of AIDS-related wasting. The approval came on the heels of a meeting with AIDS activists, Serono Laboratories, and the FDA. Serono committed, at the meeting's conclusion, to submit finalized documents to the FDA within a week. ACT UP Golden Gate won a victory when the wholesale price cap of the drug was set at $36,000.00 annually, despite the company's original demand of $75,000.00 or more.

  11. Biological effects of growth hormone and its antagonist.

    PubMed

    Okada, S; Kopchick, J J

    2001-03-01

    Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and has been implicated in diabetic eye and kidney damage. Additionally the GH/IGF-1 system has been postulated as a risk factor for several types of cancers. Thus both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago the first drug of a new class, a GH antagonist, was discovered. This molecule is now being tested for its ability to combat the effects of high circulating levels of GH. Here, we discuss some of the detrimental actions of GH, and how a GH antagonist can be used to combat these effects. PMID:11286784

  12. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  13. Molecular mechanisms of regulation of growth hormone gene expression in cultured rat pituitary cells by thyroid and glucocorticoid hormones

    SciTech Connect

    Yaffe, B.M.

    1989-01-01

    In cultured GC cells, a rat pituitary tumor cell line, growth hormone (GH) is induced in a synergistic fashion by physiologic concentrations of thyroid and glucocorticoid hormones. Abundant evidence indicates that these hormones mediate this response via their specific receptors. The purpose of this thesis is to explore the mechanisms by which these hormones affect GH production. When poly (A){sup +} RNA was isolated from cells grown both with and without hormones and translated in a cell-free wheat germ system, the preGH translation products were shown to be proportional to immunoassayable GH production under all combinations of hormonal milieux, indicating that changes in GH production is modulated at a pretranslational level. A cDNA library was constructed from poly (A){sup +}RNA and one clone containing GH cDNA sequences was isolated. This was used to confirm the above results by Northern dot blot analysis. This probe was also used to assess hormonal effects on GH mRNA half-life and synthetic rates as well as GH gene transcription rates in isolated nuclei. Using a pulse-chase protocol in which cellular RNA was labeled in vivo with ({sup 3}H)uridine, and quantitating ({sup 3}H)GHmRNA directly by hybridization to GH cDNA bound to nitrocellulose filters, GHmRNA was found to have a half-life of approximately 50 hours, and was not significantly altered by the presence of inducing hormones.

  14. Purification of a recombinant human growth hormone by an integrated IMAC procedure.

    PubMed

    Mooney, Jane T; Fredericks, Dale P; Zhang, Chunfang; Christensen, Thorkild; Jespergaard, Christina; Schiødt, Christine Bruun; Hearn, Milton T W

    2014-02-01

    In this study, integration of three discrete process aspects of the IMAC purification of Escherichia coli expressed recombinant proteins has been investigated. To this end, novel N-terminally tagged human growth hormone variants (tagged-vhGHs) have been expressed in E. coli by tank fermentation and captured directly from the cell lysate by a new IMAC approach. The chelating ligands used were 1,4,7-triaza-cyclononane (tacn) and bis(1,4,7-triazacyclononyl)-propane (dtnp) with copper(II) as the immobilised metal ion. The N-terminal tags were specifically selected for their potential to bind to these immobilised complexes and also for their ease of removal from the tagged protein by the dipeptidyl peptidase, DAP-1. Low levels of detergents in the binding buffer did not dramatically affect the purification, but increased concentrations of NaCl in the loading buffer improved the binding performance. The same IMAC systems, operated in the 'negative' adsorption chromatographic mode, could be used to obtain the purified mature human growth hormone variant, as assessed by MALDI-TOF and N-terminal sequencing studies, following removal of the affinity tag by the dipeptidyl peptidase 1. Western immunoblot analysis of the eluted fractions of both the tagged and de-tagged vhGH demonstrated significant clearance of E. coli host cell proteins (HCPs). Further, these IMAC resins can be used multiple times without the need for metal ion re-charging between runs. This study thus documents an integrated approach for the purification of specifically tagged recombinant proteins expressed in genetically modified E. coli.

  15. Changes in plasma growth hormone (GH) and secretion patterns of GH and luteinizing hormone in buffaloes (Bubalus bubalis) during growth.

    PubMed

    Mondal, Mohan; Prakash, B S

    2004-08-01

    To assess the changes of plasma growth hormone (GH) and secretion patterns of GH and luteinizing hormone (LH) during growth in buffaloes, six growing female Murrah buffalo calves (mean age 6+/-0.9 months and body weight 66+/-6 kg) were selected. Plasma samples were collected twice a week for 52 weeks for GH and LH assay. To examine for pulsatile secretion samples were collected at 15 minutes interval for 9 hr at weeks 6 and 42 for GH and LH measurements. Plasma progesterone was also estimated in twice-a-week samples to assess whether any of the buffalo had begun ovarian cyclicity. The body weight of all animals was recorded at weekly interval. Plasma GH concentration decreased (P < 0.01) only up to week 29 and showed an increasing trend (P < 0.01) thereafter. The ratio of plasma GH to body weight declined (P < 0.01) throughout the entire experimental period. Plasma GH showed a declining trend only up to when the animals attained 155 kg body weight and thereafter showed an increasing trend (P < 0.01). Plasma GH revealed distinct pulsatile patterns of release, with a mean of 6 and 5 pulses in the 6-week and 42-week samples, respectively. The plasma LH concentrations around the 42-week time period were significantly higher (P < 0.01) than at the 6-week time period, and they exhibited pulsatility. No animal reached puberty until the end of the experiment. In summary, plasma GH levels have a definite pattern of change during growth and patterns of secretion of plasma GH and LH also have a relation with body weight in this species of animal. PMID:15554346

  16. A comparison of the growth responses following intramuscular GHRH plasmid administration versus daily growth hormone injections in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation. Plasmid c...

  17. Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling

    PubMed Central

    Lisse, Thomas S.; Hewison, Martin; Adams, John S.

    2011-01-01

    Insights from vitamin D-resistant New World primates and their human homologues as models of natural and pathological insensitivity to sterol/steroid action have uncovered a family of novel intracellular vitamin D and estrogen regulatory proteins involved in hormone action. The proteins, known as “vitamin D or estrogen response element-binding proteins”, behave as potent cis-acting, transdominant regulators to inhibit steroid receptor binding to DNA response elements and is responsible for vitamin D and estrogen resistances. This set of interactors belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family of previously known pre-mRNA-interacting proteins. This review provides new insights into the mechanism by which these novel regulators of signaling and metabolism can act to regulate responses to vitamin D and estrogen. In addition the review also describes other molecules that are known to influence nuclear receptor signaling through interaction with hormone response elements. PMID:21236284

  18. Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules

    PubMed Central

    Jacob, Reeba S.; Das, Subhadeep; Ghosh, Saikat; Anoop, Arunagiri; Jha, Narendra Nath; Khan, Tuhin; Singru, Praful; Kumar, Ashutosh; Maji, Samir K.

    2016-01-01

    Amyloids are cross-β-sheet fibrillar aggregates, associated with various human diseases and native functions such as protein/peptide hormone storage inside secretory granules of neuroendocrine cells. In the current study, using amyloid detecting agents, we show that growth hormone (GH) could be stored as amyloid in the pituitary of rat. Moreover, to demonstrate the formation of GH amyloid in vitro, we studied various conditions (solvents, glycosaminoglycans, salts and metal ions) and found that in presence of zinc metal ions (Zn(II)), GH formed short curvy fibrils. The amyloidogenic nature of these fibrils was examined by Thioflavin T binding, Congo Red binding, transmission electron microscopy and X-ray diffraction. Our biophysical studies also suggest that Zn(II) initiates the early oligomerization of GH that eventually facilitates the fibrillation process. Furthermore, using immunofluorescence study of pituitary tissue, we show that GH in pituitary significantly co-localizes with Zn(II), suggesting the probable role of zinc in GH aggregation within secretory granules. We also found that GH amyloid formed in vitro is capable of releasing monomers. The study will help to understand the possible mechanism of GH storage, its regulation and monomer release from the somatotrophs of anterior pituitary. PMID:27004850

  19. A comparative study of the effects of ranitidine and cimetidine on carbohydrate tolerance, growth hormone secretion and the hypothalamic-pituitary-gonadal axis in man.

    PubMed

    Scobie, I N; Saunders, J; Barnes, G D; Hoad, J; Wheeler, M J; Lowry, C; Sonksen, P H; Amphlett, G; Riley, A J

    1986-01-01

    The effect of chronic oral administration of cimetidine (1 g per day) and ranitidine (300 mg per day) on plasma levels of prolactin (PRL), testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) and human growth hormone was compared in 2 groups of male patients who presented with dyspeptic symptoms. Eight were treated with ranitidine and 9 with cimetidine for 4 weeks. The glucose and insulin response to a 100 g oral glucose load was also assessed. Cimetidine treatment resulted in a significant increase in plasma testosterone levels which was not found in the ranitidine group. No significant change occurred in PRL, LH, FSH, SHBG, DHT and growth hormone. There was no evidence of a significant alteration in carbohydrate metabolism.

  20. Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis

    PubMed Central

    Stiedl, Patricia; McMahon, Robert; Blaas, Leander; Stanek, Victoria; Svinka, Jasmin; Grabner, Beatrice; Zollner, Gernot; Kessler, Sonja M.; Claudel, Thierry; Müller, Mathias; Mikulits, Wolfgang; Bilban, Martin; Esterbauer, Harald; Eferl, Robert; Haybaeck, Johannes; Trauner, Michael; Casanova, Emilio

    2016-01-01

    Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion Our findings suggest that GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. PMID:25179284

  1. Growth hormone isoforms in a girl with gigantism.

    PubMed

    Ng, L L; Chasalow, F I; Escobar, O; Blethen, S L

    1999-01-01

    Several previous investigations have suggested that there may be different growth hormone isoforms in patients with acromegaly. We used three different site-specific monoclonal antibodies (MAbs) to investigate growth hormone (GH) isoforms in serum from an 8 year-old girl with a GH and prolactin secreting adenoma. The pattern of GH-immunoreactivity was dependent on the circumstances of collection. Serum obtained after oral glucose had very little cross reactivity with MAb 352 although concentrations of up to 15 micrograms/l were found with two other MAbs, 033 and 665. MAb 352 does not recognize the 20,000 dalton isoform of GH (20K) while both MAb 033 and 665 do. The same pattern of GH immunoreactivity (low MAb 352, equal and higher MAb 033 and 665) was seen in other baseline samples. In contrast, samples obtained after TRH/GnRH showed immunoreactivity patterns expected for a mixture of 22,000 dalton isoform of GH (22K) with only a small amount of 20K. GH samples obtained during sleep showed both patterns with episodic peaks with equal immunoreactivity superimposed on the basal pattern (decreased activity with MAb 352). Affinity chromatography of basal samples showed that a portion of the GH immunoreactivity was neither 22K nor 20K, although in stimulated samples, over 70% of GH was 22K or 20K GH. In conclusion, the nature of GH isoforms present in serum varies with GH concentration. These differences may contribute to the known difficulty in correlating disease activity and random GH measurements in patients with GH secreting adenomas. PMID:10392356

  2. Metabolic clearance and production rates of human growth hormone.

    PubMed

    Taylor, A L; Finster, J L; Mintz, D H

    1969-12-01

    The metabolic clearance rate (MCR) of human growth hormone (HGH) was determined by the constant infusion to equilibrium technique utilizing HGH-(125)I. 22 control subjects had a MCR of 229 +/-52 ml/min (mean +/-SD). No difference was evident between sexes, or between various age groups. Patients with acromegaly demonstrated normal MCR's. Moreover, acute elevations of plasma growth hormone concentrations in normal subjects did not alter the MCR of HGH. The MCR was relatively constant from day to day and within the day when subjects were evaluated in the supine position. In contrast, the assumption of the upright position was associated with a mean 24% decrease in the MCR. These results were contrasted with the MCR of HGH observed in a small number of patients with altered thyroid function or diabetes mellitus. In six patients with hypothyroidism the MCR (131 +/-36 ml/min) was significantly decreased (P < 0.001); whereas the MCR in eight patients with hyperthyroidism (240 +/-57 ml/min) did not differ from control subjects. The MCR in eight patients with insulin-independent diabetes mellitus (IID) (185 +/-41 ml/min) and in eight patients with insulin-dependent diabetes mellitus (IDD) (136 +/-31 ml/min) were significantly different from control subjects (P = < 0.05 and P = < 0.001, respectively). These data were interpreted to indicate that the plasma HGH-removing mechanism(s) is not saturated at physiologic plasma HGH levels, that plasma HGH levels alone may not permit distinction between variations in pituitary release of the hormone and its rate of clearance from the plasma, and that the estimation of the MCR of HGH may help clarify the mechanism of abnormal plasma HGH responses to various stimuli. Production rates of HGH (PR) in control subjects (347 +/-173 mmug/min) were contrasted with hyperthyroid patients (529 +/-242 mmug/min, P < 0.05), hypothyroid patients (160 +/-69 mmug/min, P < 0.02), IID (245 +/-100 mmug/min, NS), and IDD (363 +/-153 mmug/min, NS

  3. Growth patterns and the use of growth hormone in the mucopolysaccharidoses

    PubMed Central

    Polgreen, L.E.; Miller, B.S.

    2010-01-01

    Short stature is characteristic of patients with mucopolysaccharidosis (MPS) diseases. For children with skeletal dysplasias, such as MPS, it is important to know the natural history of growth. An understanding of the natural growth pattern in each MPS disease provides a measurement to which treatments can be compared, as well as data which can help families and providers make individualized decisions about growth promoting treatments. Multiple advancements have been made in the treatment of MPS with both hematopoietic cell transplantation (HCT) and enzyme replacement therapy (ERT). The long term benefit of these treatments on growth is unknown. This article will review the published data on growth in children with MPS, and describe preliminary data on the use of human growth hormone (hGH) in children with MPS. PMID:20563263

  4. Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease.

    PubMed

    Rodriguez, Santiago; Gaunt, Tom R; Day, Ian N M

    2007-08-01

    The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2 genes (IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This "growth pathway" also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits. PMID:17534663

  5. Isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus) growth hormone.

    PubMed

    Ayson, F G; de Jesus, E G; Amemiya, Y; Moriyama, S; Hirano, T; Kawauchi, H

    2000-02-01

    We report the isolation, cDNA cloning, and growth promoting activity of rabbitfish (Siganus guttatus; Teleostei; Perciformes; Siganidae) growth hormone (GH). Rabbitfish GH was extracted from pituitary glands under alkaline conditions, fractionated by gel filtration chromatography on Sephadex G-100, and purified by high-performance liquid chromatography. The fractions containing GH were identified by immunoblotting with bonito GH antiserum. Under nonreducing conditions, the molecular weight of rabbitfish GH is about 19 kDa as estimated by SDS-PAGE. The purified hormone was potent in promoting growth in rabbitfish fry. Weekly intraperitoneal injections of the hormone significantly accelerated growth. This was evident 3 weeks after the start of the treatment, and its effect was still significant 2 weeks after the treatment was terminated. Rabbitfish GH cDNA was cloned to determine its nucleotide sequence. Excluding the poly (A) tail, rabbitfish GH cDNA is 860 base pairs (bp) long. It contained untranslated regions of 94 and 175 bp in the 5' and 3' ends, respectively. It has an open reading frame of 588 bp coding for a signal peptide of 18 amino acids and a mature protein of 178 amino acid residues. Rabbitfish GH has 4 cysteine residues. On the amino acid level, rabbitfish GH shows high identity (71-74%) with GHs of other perciforms, such as tuna, sea bass, yellow tail, bonito, and tilapia, and less (47-49%) identity with salmonid and carp GHs.

  6. Osteocalcin induces growth hormone/insulin-like growth factor-1 system by promoting testosterone synthesis in male mice.

    PubMed

    Li, Y; Li, K

    2014-10-01

    Osteocalcin has been shown to enhance testosterone production in men. In the present study, we investigated the effects of osteocalcin on testosterone and on induction of the growth hormone/insulin-like growth factor-1 axis. Osteocalcin injection stimulated growth, which could be inhibited by castration. In addition, osteocalcin induced testosterone secretion in testes both in vivo and in vitro. Using real-time polymerase chain reaction and Western blotting, we showed that growth hormone expression was significantly increased in the pituitary after osteocalcin injection (p<0.05). Growth hormone expression in CLU401 mouse pituitary cells was also significantly stimulated (p<0.05) by osteocalcin-induced MA-10 cells. Osteocalcin injection also promoted hepatic expression of growth hormone receptor and insulin-like growth factor-1 (p<0.05), as demonstrated by real-time polymerase chain reaction and Western blotting. Similarly, osteocalcin-induced MA-10 cells promoted growth hormone receptor and insulin-like growth factor-1 expression in NCTC1469 cells. These results suggest that the growth-stimulating activities of osteocalcin are mediated by testicular testosterone secretion, and thus provide valuable information regarding the regulatory effects of osteocalcin expression on the growth hormone/insulin-like growth factor-1 axis via reproductive activities.

  7. Gibberellin hormone signal perception: down-regulating DELLA repressors of plant growth and development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gibberellin (GA) hormone signal is perceived by a receptor with homology to hormone sensitive lipases, GID1 (GA-INSENSITIVE DWARF1). This leads to GA-stimulated responses including stem elongation, seed germination, and the transition to flowering. GA-binding enables GID1 to interact with and ...

  8. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  9. Rasch Measurement in the Assessment of Growth Hormone Deficiency in Adult Patients.

    ERIC Educational Resources Information Center

    Prieto, Luis; Roset, Montse; Badia, Xavier

    2001-01-01

    Tested the metric properties of a Spanish version of the Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire through Rasch analysis with a sample of 356 adult patients in Spain. Results suggest that the Spanish AGHDA could be a useful complement of the clinical evaluation of growth hormone deficiency patients at group and…

  10. Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly.

    PubMed

    Asa, S L; Bilbao, J M; Kovacs, K; Linfoot, J A

    1980-01-01

    A hypothalamic neuronal hamartoma associated with a sparsely granulated growth hormone cell adenoma of the pituitary and acromegaly is reported. It is suggested that the patient had a primary neuronal tumor, whose neurosecretory activity promoted the development of the growth hormone secreting pituitary adenoma causing acromegaly.

  11. Gigantism caused by growth hormone secreting pituitary adenoma.

    PubMed

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-06-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

  12. Juvenile hormone regulates extreme mandible growth in male stag beetles.

    PubMed

    Gotoh, Hiroki; Cornette, Richard; Koshikawa, Shigeyuki; Okada, Yasukazu; Lavine, Laura Corley; Emlen, Douglas J; Miura, Toru

    2011-01-01

    The morphological diversity of insects is one of the most striking phenomena in biology. Evolutionary modifications to the relative sizes of body parts, including the evolution of traits with exaggerated proportions, are responsible for a vast range of body forms. Remarkable examples of an insect trait with exaggerated proportions are the mandibular weapons of stag beetles. Male stag beetles possess extremely enlarged mandibles which they use in combat with rival males over females. As with other sexually selected traits, stag beetle mandibles vary widely in size among males, and this variable growth results from differential larval nutrition. However, the mechanisms responsible for coupling nutrition with growth of stag beetle mandibles (or indeed any insect structure) remain largely unknown. Here, we demonstrate that during the development of male stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are correlated with the extreme growth of an exaggerated weapon of sexual selection. We then investigate the putative role of JH in the development of the nutritionally-dependent, phenotypically plastic mandibles, by increasing hemolymph titers of JH with application of the JH analog fenoxycarb during larval and prepupal developmental periods. Increased JH signaling during the early prepupal period increased the proportional size of body parts, and this was especially pronounced in male mandibles, enhancing the exaggerated size of this trait. The direction of this response is consistent with the measured JH titers during this same period. Combined, our results support a role for JH in the nutrition-dependent regulation of extreme mandible growth in this species. In addition, they illuminate mechanisms underlying the evolution of trait proportion, the most salient feature of the evolutionary diversification of the insects.

  13. Gigantism caused by growth hormone secreting pituitary adenoma

    PubMed Central

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

    2014-01-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

  14. Gigantism caused by growth hormone secreting pituitary adenoma.

    PubMed

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-06-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  15. Optimization of the purification methods for recovery of recombinant growth hormone from Paralichthys olivaceus

    NASA Astrophysics Data System (ADS)

    Zang, Xiaonan; Zhang, Xuecheng; Mu, Xiaosheng; Liu, Bin

    2013-03-01

    This study aimed to optimize the purification of recombinant growth hormone from Paralichthys olivaceus. Recombinant flounder growth hormone (r-fGH) was expressed by Escherichia coli in form of inclusion body or as soluble protein under different inducing conditions. The inclusion body was renatured using two recovery methods, i.e., dilution and dialysis. Thereafter, the refolded protein was purified by Glutathione Sepharase 4B affinity chromatography and r-fGH was obtained by cleavage of thrombin. For soluble products, r-fGH was directly purified from the lysates by Glutathione Sepharase 4B affinity chromatography. ELISA-receptor assay demonstrated that despite its low receptor binding activity, the r-fGH purified from refolded inclusion body had a higher yield (2.605 mg L-1) than that from soluble protein (1.964 mg L-1). Of the tested recovery methods, addition of renaturing buffer (pH 8.5) into denatured inclusion body yielded the best recovery rate (17.9%). This work provided an optimized purification method for high recovery of r-fGH, thus contributing to the application of r-fGH to aquaculture.

  16. A study of cell electrophoresis as a means of purifying growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Plank, Lindsay D.; Hymer, W. C.; Kunze, M. Elaine; Marks, Gary M.; Lanham, J. Wayne

    1983-01-01

    Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partialy purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.

  17. Hormone-Mediated Pattern Formation in Seedling of Plants: a Competitive Growth Dynamics Model

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Oikawa, Noriko; Okabe, Hirotaka; Kai, Shoichi

    2001-10-01

    An ecologically relevant pattern formation process mediated by hormonal interactions among growing seedlings is modeled based on the experimental observations on the effects of indole acetic acid, which can act as an inhibitor and activator of root growth depending on its concentration. In the absence of any lateral root with constant hormone-sensitivity, the edge effect phenomenon is obtained depending on the secretion rate of hormone from the main root. Introduction of growth-stage-dependent hormone-sensitivity drastically amplifies the initial randomness, resulting in spatially irregular macroscopic patterns. When the lateral root growth is introduced, periodic patterns are obtained whose periodicity depends on the length of lateral roots. The growth-stage-dependent hormone-sensitivity and the lateral root growth are crucial for macroscopic periodic-pattern formation.

  18. Growth hormone receptor antagonists: discovery and potential uses.

    PubMed

    Kopchick, J J; Okada, S

    2001-06-01

    Serum levels of growth hormone (GH) in the human body vary and can influence the levels of insulin-like growth factor I (IGF-1). Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly, and also have been implicated in diabetic eye and kidney damage. Additionally, it has been postulated that the GH-IGF-I system can be involved in several types of cancers. Overall, both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago a new class of drug, a GH antagonist, was discovered. It is now being tested for its ability to combat the effects of high circulating levels of GH. In this review, we will discuss some of the detrimental actions of GH and how a GH antagonist may be used to combat these effects. PMID:11527080

  19. Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary.

    PubMed Central

    Fischer, J A; Tobler, P H; Kaufmann, M; Born, W; Henke, H; Cooper, P E; Sagar, S M; Martin, J B

    1981-01-01

    Immunoreactive calcitonin (CT), indistinguishable from human CT-(1-32) and its sulfoxide, has been identified in extracts of the hypothalamus, the pituitary, and the thyroid obtained from human subjects at autopsy. DCT concentrations were highest in a region encompassing the posterior hypothalamus, the median eminence, and the pituitary; intermediate in the substantia nigra, the anterior hypothalamus, the globus pallidus, and the inferior colliculus; and low in the caudate nucleus, the hippocampus, the amygdala, and the cerebral and cerebellar cortices. Specific CT binding measured with 125I-labeled salmon CT was highest in homogenates of the posterior hypothalamus and the median eminence, shown to contain the highest concentrations of endogenous CT in the brain; CT binding was less than 12% of hypothalamic binding in all of the other regions of the brain examined and was negligible in the pituitary. Half-maximal binding was achieved with 0.1 nM nonradioactive salmon CT-(1-32), and the binding was directed to structural or conformational sites, or both, in the COOH-terminal half of salmon CT. The rank order of the inhibition of the binding by CT from different species and analogues of the human hormone was the same as in receptors on a human lymphoid cell line (Moran, J., Hunziker, W. & Fischer, J. A. (1978) Proc. Natl. Acad. Sci. USA 75, 3984-3988). The functional role of CT and of its binding sites in the brain remains to be elucidated. PMID:6950419

  20. Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin.

    PubMed

    Lin, Hai-Yan; Muller, Yves A; Hammond, Geoffrey L

    2010-03-01

    Corticosteroid-binding globulin (CBG), a non-inhibitory member of the serine proteinase inhibitor (serpin) super-family, is the high-affinity transport protein for glucocorticoids in vertebrate blood. Plasma CBG is a glycoprotein with 30% of its mass represented by N-linked oligosaccharide chains. Its well-characterized steroid-binding properties represent a "bench-mark data set" used extensively for in silico studies of protein-ligand interactions and drug design. Recent crystal structure analyses of intact rat CBG and cleaved human CBG have revealed the precise topography of the steroid-binding site, and shown that cortisol-bound CBG displays a typical stressed (S) serpin conformation with the reactive center loop (RCL) fully exposed from the central beta-sheet A, while proteolytic cleavage of the RCL results in CBG adopting a relaxed (R) conformation with the cleaved RCL fully inserted within the protein core. These crystal structures have set the stage for mechanistic studies of CBG function which have so far shown that helix D plays a key role in coupling RCL movement and steroid-binding site integrity, and provided evidence for an allosteric mechanism that modulates steroid binding and release from CBG. These studies have also revealed how the irreversible release of steroids occurs after proteolysis and re-orientation of the RCL within the R conformation. This recent insight into the structure and function of CBG reveals how naturally occurring genetic CBG mutations affect steroid binding, and helps understand how proteolysis of CBG enhances the targeted delivery of biologically active steroids to their sites of action.

  1. Increased secretion of growth hormone, prolactin, antidiuretic hormone, and cortisol induced by the stress of motion sickness.

    PubMed

    Eversmann, T; Gottsmann, M; Uhlich, E; Ulbrecht, G; von Werder, K; Scriba, P C

    1978-01-01

    The stress of motion sickness was experimentally provoked by Coriolis effect. Significant and reproducible increases from the basal serum level (delta mean +/- S.E.) of antidiuretic hormone delta - ADH: 48.2 +/- 4.6 pg/ml; p less than 0.0005), of growth hormone (delta - hGH: 10.0 +/- 1.2 ng/ml; p less than 0.0005), of prolactin (delta - hPRL: 186.5 +/- 29.9 muU/ml; p less than 0.0005), and of cortisol (delta - F; 12.3 +/- 0.9 microgram%; p less than 0.0005) were observed, whereas the luteinizing hormone levels did not change significantly. The stimulation of hormone secretion induced by different degrees of motion sickness seems to correlate with the severity of motion sickness. The secretion of antidiuretic hormones is the most sensitive indicator for the stress of motion sickness whereas growth hormone, prolactin, and cortisol responses to the stress of motion sickness are more delayed and less pronounced.

  2. Ghrelin and the growth hormone secretagogue receptor in growth and development.

    PubMed

    Chanoine, J-P; De Waele, K; Walia, P

    2009-04-01

    The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.

  3. Exogenous recombinant bovine growth hormone stimulates growth and hepatic IGF expression in shovelnose sturgeon Scaphirhynchus platorhynchus.

    PubMed

    Fenn, Carlin M; Small, Brian C

    2015-02-01

    Sturgeon are a unique fish for physiological research as they are long-lived, slow-growing, and late-maturing. Furthermore, sturgeon growth hormones appear to share greater structural and molecular similarity with mammalian somatotropins than teleostean somatotropins. In this study, changes in insulin-like growth factor (IGF)-I and IGF-II mRNA expression and corresponding whole-body growth and composition following 6 weeks of bi-weekly recombinant bovine growth hormone (rbGH) administration in shovelnose sturgeon Scaphirhynchus platorhynchus were evaluated. Fish were injected intraperitoneally with 240 μg rbGH/g body weight or a sesame oil sham. Hepatic IGF-I and IGF-II mRNA abundance was significantly higher (P≤0.02) in rbGH-treated fish, as were length (P<0.001) and weight gain (P<0.001). In addition, proximate whole-body analysis demonstrated a significant (P<0.05) increase in protein composition of rbGH-treated fish versus sham-treated fish. There were no significant differences in whole-body moisture, lipid, or ash between the two treatments. These results demonstrate functional roles for GH and IGFs in the promotion of lean growth within this ancient fish species and support the view that the functional effects of GH on hepatic IGF-I expression and somatic growth are conserved from chondostrean to teleostean fishes.

  4. A statistical model of diurnal variation in human growth hormone

    NASA Technical Reports Server (NTRS)

    Klerman, Elizabeth B.; Adler, Gail K.; Jin, Moonsoo; Maliszewski, Anne M.; Brown, Emery N.

    2003-01-01

    The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

  5. Metabolic response to human growth hormone during prolonged starvation

    PubMed Central

    Felig, Philip; Marliss, Errol B.; Cahill, George F.

    1971-01-01

    The metabolic response to human growth hormone (HGH) was studied in five obese subjects in the fed state and during prolonged (5-6 wk) starvation. In the fed state (three subjects), HGH induced an elevation in basal serum insulin concentration, a minimal increase in blood and urine ketone levels, and a marked reduction in urinary nitrogen and potassium excretion resulting in positive nitrogen and potassium balance. In prolonged fasting (four subjects), HGH administration resulted in a 2- to 3-fold increase in serum insulin which preceded a 50% elevation in blood glucose. Persistence of the lipolytic effects of HGH was indicated by a rise in free fatty acids and glycerol. The response differed markedly from the fed state in that blood β-hydroxybutyrate and acetoacetate levels rose by 20-40%, resulting in total blood ketone acid concentrations of 10-12 mmoles/liter, ketonuria of 150-320 mmoles/day, and increased urinary potassium loss. The subjects complained of nausea, vomiting, weakness, and myalgias. Despite a 50% reduction in urea excretion during HGH administration, total nitrogen loss remained unchanged as urinary ammonia excretion rose by 50% and correlated directly with the degree of ketonuria. It is concluded that in prolonged starvation (a) HGH may have a direct insulinotropic effect on the beta cell independent of alterations in blood glucose concentration, (b) persistence of the lipolytic action of HGH results in severe exaggeration of starvation ketosis and interferes with its anticatabolic action by necessitating increased urinary ammonia loss, and (c) failure of HGH to reduce net protein catabolism in starvation suggests that this hormone does not have a prime regulatory role in conserving body protein stores during prolonged fasting. PMID:5540176

  6. Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies

    PubMed Central

    Csiszar, Anna; de Cabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-01-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span. PMID:22522510

  7. Growth hormone and drug metabolism. Acute effects on nuclear ribonucleic acid polymerase activity and chromatin.

    PubMed Central

    Spelsberg, T C; Wilson, J T

    1976-01-01

    Adult male rats, subjected either to sham operation or to hypophysectomy and adrenalectomy were maintained for 10 days before treatment with growth hormone. Results of the acute effects of growth hormone on the rat liver nuclear RNA polymerase I (nucleolar) and II (nucleoplasmic) activities as well as the chromatin template capacity were then studied and compared with the growth-hormone effects on the drug metabolism described in the preceding paper (Wilson & Spelsberg, 1976). 2. Conditions for isolation and storage of nuclei for maintenance of optimal polymerase activities are described. It is verified that the assays for polymerase activities require a DNA template, all four nucleoside triphosphates, and a bivalent cation, and that the acid-insoluble radioactive product represents RNA. Proof is presented that under high-salt conditions DNA-like RNA (polymerase II) is synthesized, and that under low-salt conditions in the presence of alpha-amanitin, rRNA (polymerase I) is synthesized. 3. In the livers of hypophysectomized/adrenalectomized rats, growth hormone increases the activity of both RNA polymerase enzymes and the chromatin template capacity within 1h after treatment. The effects last for 12h in the case of polymerase II but for only 6h in the case of polymerase I. Sham-operated rats respond to growth hormone in a manner somewhat similar to that shown by hypophysectomized/adrenalectomized rats. These results, which demonstrate an enhancement of RNA polymerase I activity in response to growth hormone, support those from other laboratories. 4. Growth-hormone enhancement of the chromatin template capacity in the liver of hypophysectomized/adrenalectomized rats contrasts with previous reports. The growth-hormone-induced de-repression of the chromatin DNA could represent the basis of the growth-hormone-induced enhancement of RNA polymerase II activity in the hypophysectomized/adrenalectomized rats, although some effect of growth-hormone on the polymerase enzymes

  8. The effects of stress hormones on growth of selected periodontitis related bacteria.

    PubMed

    Jentsch, H F R; März, Diana; Krüger, Monika

    2013-12-01

    The focus of this study was to examine in vitro the effects of stress hormones (catecholamines: epinephrine, norepinephrine, dopamine and hydrocortisone: cortisol) on the growth of four anaerobic species of periodontitis-related bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Tannerella forsythia) and one facultative anaerobic species (Eikenella corrodens). Bacterial growth was determined by two different methods: fluorescence in situ hybridization (FISH), and the viable count by culture method. To simulate stress, each single strain was grown in a special growth medium with three different concentrations of each hormone, using an anaerobic chamber at 37 °C. Growth of F. nucleatum increased in the presence of all stress hormones. Growth of P. gingivalis was not significantly influenced by any hormone. Growth of P. intermedia and E. corrodens was inhibited by almost all stress hormones tested. Both methods of analysis revealed that the highest concentrations of norepinephrine and cortisol increased the growth of T. forsythia. Different hormones have a different effect on the growth of periodontitis-related bacteria in vitro. It appears that bacterial viability is more strongly influenced than is bacterial metabolic activity. The growth of F. nucleatum particularly and partially of T. forsythia is increased by several stress hormones and may have an additional negative impact on periodontal disease.

  9. Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates.

    PubMed

    Tine, Mbaye; Kuhl, Heiner; Teske, Peter R; Tschöp, Matthias H; Jastroch, Martin

    2016-04-01

    The gut hormone ghrelin is involved in numerous metabolic functions, such as the stimulation of growth hormone secretion, gastric motility, and food intake. Ghrelin is modified by ghrelin O-acyltransferase (GOAT) or membrane-bound O-acyltransferase domain-containing 4 (MBOAT4) enabling action through the growth hormone secretagogue receptors (GHS-R). During the course of evolution, initially strong ligand/receptor specificities can be disrupted by genomic changes, potentially modifying physiological roles of the ligand/receptor system. Here, we investigated the coevolution of ghrelin, GOAT, and GHS-R in vertebrates. We combined similarity search, conserved synteny analyses, phylogenetic reconstructions, and protein structure comparisons to reconstruct the evolutionary history of the ghrelin system. Ghrelin remained a single-gene locus in all vertebrate species, and accordingly, a single GHS-R isoform was identified in all tetrapods. Similar patterns of the nonsynonymous (dN) and synonymous (dS) ratio (dN/dS) in the vertebrate lineage strongly suggest coevolution of the ghrelin and GHS-R genes, supporting specific functional interactions and common physiological pathways. The selection profiles do not allow confirmation as to whether ghrelin binds specifically to GOAT, but the ghrelin dN/dS patterns are more similar to those of GOAT compared to MBOAT1 and MBOAT2 isoforms. Four GHS-R isoforms were identified in teleost genomes. This diversification of GHS-R resulted from successive rounds of duplications, some of which remained specific to the teleost lineage. Coevolution signals are lost in teleosts, presumably due to the diversification of GHS-R but not the ghrelin gene. The identification of the GHS-R diversity in teleosts provides a molecular basis for comparative studies on ghrelin's physiological roles and regulation, while the comparative sequence and structure analyses will assist translational medicine to determine structure-function relationships of the

  10. Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome.

    PubMed Central

    Schaefer, G B; Rosenbloom, A L; Guevara-Aguirre, J; Campbell, E A; Ullrich, F; Patil, K; Frias, J L

    1994-01-01

    Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency. Images PMID:7815422

  11. Hormone-dependent Model on Seed Germination Sensitive to Growth Stage

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Satoshi; Mimura, Masayasu; Ohya, Tomoyuki; Okabe, Hirotaka; Kai, Shoichi

    2000-04-01

    In the germination of seeds, there often observes cluster-formation of well-grown roots and the edge effect phenomenon.During germination and growth before starting photosynthesis, direct interaction such as competition for nutrition among hosts is rather weak because of self-supplying of nutrition.Instead, hormones play an important role and may cause the above experimental observations.In order to understand these aspects, we propose a growth model for root.The hormone effect and its growth-stage-dependent sensitivity are taken into consideration.It is discussed how the growth process of grouping roots is influenced by exogenous hormones secreted from roots.

  12. Monoclonal antibodies to human growth hormone induce an allosteric conformational change in the antigen.

    PubMed Central

    Mazza, M M; Retegui, L A

    1989-01-01

    We re-investigated the properties of a monoclonal antibody (mAb), 4D11, to human growth hormone (hGH) that showed a very weak affinity, recognizing hGH only when the hormone was solubilized on a solid surface. MAb4D11 did not significantly bind 125I-hGH. It was found that three mAb directed to different hGH epitopes (mAb 3C11, 10C1 and NA71) were able to induce the binding of the soluble antigen to mAb 4D11. The co-operative effect could be demonstrated by the formation of binary complexes (Ag:Ab, 1:2) detected by high-performance liquid chromatography (HPLC) and by the increase of radioactivity found when the synergistic mAb were added to 125I-hGH incubated with mAb 4D11 immobilized on polyvinyl microplates. Other possible explanations, such as the formation of cyclic complexes or the generation of a new epitope in the Fc fragment of the first antibody (Ab), were dismissed because the Fab fragment of one of the enhancing mAb (3C11) gave the same effect as the intact Ab. The data suggest that the hGH molecule undergoes a localized conformational change after binding to mAb 3C11, NA71 or 10C1 and that mAb 4D11 binds with high affinity to the modified region of the hormone. The formation or not of ternary complexes (Ag:Ab, 1:3) was used to localize the 4D11 epitope on the surface of the Ag. It is suggested that mAb 4D11 recognizes a conformational change produced in the region defined by the AE5/AC8 epitopes, which is close to the hGH antigenic domain only expressed when the protein is immobilized on plastic surfaces. PMID:2473953

  13. Novel Drosophila receptor that binds multiple growth factors

    SciTech Connect

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-05-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10/sup -6/ to 10/sup -8/ M. The 100 kDa protein can be affinity-labeled with these /sup 125/I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by /sup 125/I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors.

  14. Protective Role of Growth Hormone against Hyperhomocysteinemia Induced Glomerular Injury

    PubMed Central

    Li, Caixia; Xia, Min; Abais, Justine M.; Liu, Xiaocheng; Li, Ningjun; Boini, Krishna M.; Li, Pin-Lan

    2013-01-01

    The present study investigated the protective role of growth hormone (GH) against hyperhomocysteinemia (hHcys)-induced activations of reactive oxygen species (ROS)/hypoxia-inducible factor (HIF)-1α, epithelial-mesenchymal transition (EMT) and consequent glomerular injury. A hyperhomocysteinemia (hHcys) model was induced by folate free (FF) diet in mice. The urine protein excretion significantly increased while plasma GH levels dramatically decreased in hHcys. Real time RT-PCR showed that GH receptor (GHR) level increased in the cortex of hHcys mice, which mainly occurred in podocytes as shown by confocal microscopy. Recombinant mouse growth hormone (rmGH) treatment (0.02 mg/kg, once a day for 6 weeks) significantly restored the plasma GH, inhibited GHR up-regulation and attenuated proteinuria. Correspondingly, rmGH treatment also blocked hHcys-induced decrease in the expression of podocin, a podocyte slit diaphragm molecule, and inhibited the increases in the expression of desmin, a podocyte injury marker. It was also demonstrated that in hHcys the expression of epithelial markers, p-cadherin and ZO-1, decreased, while the expression of mesenchymal markers, FSP-1 and α-SMA, increased in podocytes, which together suggest the activation of EMT in podocytes. NADPH oxidase (Nox)-dependent superoxide anion (O2·−) and HIF-1α level in the hHcys mice cortex was markedly enhanced. These hHcys-induced EMT enhancement and Nox-dependant O2·−/HIF-1α activation were significantly attenuated by rmGH treatment. HIF-1α level increased in Hcys-treated cultured podocytes, which were blocked by rmGH treatment. Meanwhile, Hcys-induced EMT in cultured podocytes was significantly reversed by HIF-1α siRNA. All these results support the view that GH ameliorates hHcys-induced glomerular injury by reducing Nox-dependent O2·−/HIF-1α signal pathway and EMT. PMID:23529346

  15. Diverse Roles for Sex Hormone-Binding Globulin in Reproduction1

    PubMed Central

    Hammond, Geoffrey L.

    2011-01-01

    Sex hormone-binding globulin (SHBG) transports androgens and estrogens in blood and regulates their access to target tissues. Hepatic production of SHBG fluctuates throughout the life cycle and is influenced primarily by metabolic and hormonal factors. Genetic differences also contribute to interindividual variations in plasma SHBG levels. In addition to controlling the plasma distribution, metabolic clearance, and bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts novel effects on androgen and estrogen action. In mammals, the gene-encoding SHBG is expressed primarily in the liver but also at low levels in other tissues, including the testis. In subprimate species, Shbg expression in Sertoli cells is under the control of follicle-stimulating hormone and produces the androgen-binding protein that influences androgen actions in the seminiferous tubules and epididymis. In humans, the SHBG gene is not expressed in Sertoli cells, but its expression in germ cells produces an SHBG isoform that accumulates in the acrosome. In fish, Shbg is produced by the liver but has a unique function in the gill as a portal for natural steroids and xenobiotics, including synthetic steroids. However, salmon have retained a second, poorly conserved Shbg gene that is expressed only in ovary, muscle, and gill and that likely exerts specialized functions in these tissues. The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction. PMID:21613632

  16. Egg size-dependent expression of growth hormone receptor accompanies compensatory growth in fish

    PubMed Central

    Segers, F. H. I. D.; Berishvili, G.; Taborsky, B.

    2012-01-01

    Large egg size usually boosts offspring survival, but mothers have to trade off egg size against egg number. Therefore, females often produce smaller eggs when environmental conditions for offspring are favourable, which is subsequently compensated for by accelerated juvenile growth. How this rapid growth is modulated on a molecular level is still unclear. As the somatotropic axis is a key regulator of early growth in vertebrates, we investigated the effect of egg size on three key genes belonging to this axis, at different ontogenetic stages in a mouthbrooding cichlid (Simochromis pleurospilus). The expression levels of one of them, the growth hormone receptor (GHR), were significantly higher in large than in small eggs, but remarkably, this pattern was reversed after hatching: young originating from small eggs had significantly higher GHR expression levels as yolk sac larvae and as juveniles. GHR expression in yolk sac larvae was positively correlated with juvenile growth rate and correspondingly fish originating from small eggs grew faster. This enabled them to catch up fully in size within eight weeks with conspecifics from larger eggs. This is the first evidence for a potential link between egg size, an important maternal effect, and offspring gene expression, which mediates an adaptive adjustment in a relevant hormonal axis. PMID:21752823

  17. Growth hormone signaling is necessary for lifespan extension by dietary methionine.

    PubMed

    Brown-Borg, Holly M; Rakoczy, Sharlene G; Wonderlich, Joseph A; Rojanathammanee, Lalida; Kopchick, John J; Armstrong, Vanessa; Raasakka, Debbie

    2014-12-01

    Growth hormone significantly impacts lifespan in mammals. Mouse longevity is extended when growth hormone (GH) signaling is interrupted but markedly shortened with high-plasma hormone levels. Methionine metabolism is enhanced in growth hormone deficiency, for example, in the Ames dwarf, but suppressed in GH transgenic mice. Methionine intake affects also lifespan, and thus, GH mutant mice and respective wild-type littermates were fed 0.16%, 0.43%, or 1.3% methionine to evaluate the interaction between hormone status and methionine. All wild-type and GH transgenic mice lived longer when fed 0.16% methionine but not when fed higher levels. In contrast, animals without growth hormone signaling due to hormone deficiency or resistance did not respond to altered levels of methionine in terms of lifespan, body weight, or food consumption. Taken together, our results suggest that the presence of growth hormone is necessary to sense dietary methionine changes, thus strongly linking growth and lifespan to amino acid availability.

  18. Rational Design of Potent Antagonists to the Human Growth Hormone Receptor

    NASA Astrophysics Data System (ADS)

    Fuh, Germaine; Cunningham, Brian C.; Fukunaga, Rikiro; Nagata, Shigekazu; Goeddel, David V.; Wells, James A.

    1992-06-01

    A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially-a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.

  19. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    SciTech Connect

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo; Tabaei, Seyed M.H.; Miguel-Queralt, Solange; Underhill, Caroline; Cherkasov, Artem Hammond, Geoffrey L.

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.

  20. Plant hormone jasmonate prioritizes defense over growth by interfering with gibberellin signaling cascade.

    PubMed

    Yang, Dong-Lei; Yao, Jian; Mei, Chuan-Sheng; Tong, Xiao-Hong; Zeng, Long-Jun; Li, Qun; Xiao, Lang-Tao; Sun, Tai-ping; Li, Jigang; Deng, Xing-Wang; Lee, Chin Mei; Thomashow, Michael F; Yang, Yinong; He, Zuhua; He, Sheng Yang

    2012-05-01

    Plants must effectively defend against biotic and abiotic stresses to survive in nature. However, this defense is costly and is often accompanied by significant growth inhibition. How plants coordinate the fluctuating growth-defense dynamics is not well understood and remains a fundamental question. Jasmonate (JA) and gibberellic acid (GA) are important plant hormones that mediate defense and growth, respectively. Binding of bioactive JA or GA ligands to cognate receptors leads to proteasome-dependent degradation of specific transcriptional repressors (the JAZ or DELLA family of proteins), which, at the resting state, represses cognate transcription factors involved in defense (e.g., MYCs) or growth [e.g. phytochrome interacting factors (PIFs)]. In this study, we found that the coi1 JA receptor mutants of rice (a domesticated monocot crop) and Arabidopsis (a model dicot plant) both exhibit hallmark phenotypes of GA-hypersensitive mutants. JA delays GA-mediated DELLA protein degradation, and the della mutant is less sensitive to JA for growth inhibition. Overexpression of a selected group of JAZ repressors in Arabidopsis plants partially phenocopies GA-associated phenotypes of the coi1 mutant, and JAZ9 inhibits RGA (a DELLA protein) interaction with transcription factor PIF3. Importantly, the pif quadruple (pifq) mutant no longer responds to JA-induced growth inhibition, and overexpression of PIF3 could partially overcome JA-induced growth inhibition. Thus, a molecular cascade involving the COI1-JAZ-DELLA-PIF signaling module, by which angiosperm plants prioritize JA-mediated defense over growth, has been elucidated.

  1. Measuring growth hormone and insulin-like growth factor-I in infants: what is normal?

    PubMed

    Hawkes, Colin Patrick; Grimberg, Adda

    2013-12-01

    The role of growth hormone (GH) and insulinlike growth factor-I (IGF-I) change through early childhood. Whereas poor growth is a later presenting feature, infants with isolated GH deficiency have a normal birth weight and length, and often present with hypoglycemia. IGF-I plays an important role antenatally and post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis in infancy, an understanding of the normal physiology is required. Measurements of GH and IGF-I in this population should be interpreted in the context of the assays used, as well as their limitations. In this review, we summarize our current understanding of normal GH and IGF-I secretion in children under 18 months of age, and describe variations in the reported assay-specific measurements.

  2. Measuring Growth Hormone and Insulin-like Growth Factor-I in Infants: What is Normal?

    PubMed Central

    Hawkes, Colin Patrick; Grimberg, Adda

    2014-01-01

    The role of growth hormone (GH) and insulin-like growth factor-I (IGF-I) change through early childhood. Whereas poor growth is a later presenting feature, infants with isolated GH deficiency have a normal birth weight and length, and often present with hypoglycemia. IGF-I plays an important role antenatally and post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis in infancy, an understanding of the normal physiology is required. Measurements of GH and IGF-I in this population should be interpreted in the context of the assays used, as well as their limitations. In this review, we summarize our current understanding of normal GH and IGF-I secretion in children under 18 months of age, and describe variations in the reported assay-specific measurements. PMID:24575549

  3. Identification of thyroid hormone receptor binding sites in developing mouse cerebellum

    PubMed Central

    2013-01-01

    Background Thyroid hormones play an essential role in early vertebrate development as well as other key processes. One of its modes of action is to bind to the thyroid hormone receptor (TR) which, in turn, binds to thyroid response elements (TREs) in promoter regions of target genes. The sequence motif for TREs remains largely undefined as does the precise chromosomal location of the TR binding sites. A chromatin immunoprecipitation on microarray (ChIP-chip) experiment was conducted using mouse cerebellum post natal day (PND) 4 and PND15 for the thyroid hormone receptor (TR) beta 1 to map its binding sites on over 5000 gene promoter regions. We have performed a detailed computational analysis of these data. Results By analysing a recent spike-in study, the optimal normalization and peak identification approaches were determined for our dataset. Application of these techniques led to the identification of 211 ChIP-chip peaks enriched for TR binding in cerebellum samples. ChIP-PCR validation of 25 peaks led to the identification of 16 true positive TREs. Following a detailed literature review to identify all known mouse TREs, a position weight matrix (PWM) was created representing the classic TRE sequence motif. Various classes of promoter regions were investigated for the presence of this PWM, including permuted sequences, randomly selected promoter sequences, and genes known to be regulated by TH. We found that while the occurrence of the TRE motif is strongly correlated with gene regulation by TH for some genes, other TH-regulated genes do not exhibit an increased density of TRE half-site motifs. Furthermore, we demonstrate that an increase in the rate of occurrence of the half-site motifs does not always indicate the specific location of the TRE within the promoter region. To account for the fact that TR often operates as a dimer, we introduce a novel dual-threshold PWM scanning approach for identifying TREs with a true positive rate of 0.73 and a false positive

  4. Characterization of insulin-like growth factor-binding proteins from sheep thyroid cells.

    PubMed

    Bachrach, L K; Liu, F R; Burrow, G N; Eggo, M C

    1989-12-01

    The insulin-like growth factors (IGFs) are bound by specific, high affinity binding proteins. Distinct classes of IGF-binding proteins have been described in human serum, amniotic fluid, cerebrospinal fluid, and conditioned medium from cultured cells. Sheep thyroid cells produce IGF-binding proteins under hormonal regulation. Cells grown without or with standard medium supplements (transferrin, glycyl-histidyl-lysine, hydrocortisone, somatostatin, insulin, and TSH) released binding proteins with apparent mol wt of 23, 29, and 32 kDa on Western ligand blot (nonreduced). Binding proteins from these cells appeared as 21, 26, 34, 36, and 41 kDa bands when cross-linked to [125I]IGF-I under reducing conditions. The addition of epidermal growth factor (EGF) or phorbol esters, thyroid cell mitogens stimulated the production of larger binding proteins with mol wt of 40-44 and 48-52 by ligand blot and cross-linking methods, respectively. Deglycosylation of conditioned medium cross-linked to [125I]IGF-I with endoglycosidase-F did not alter the size of the smaller binding proteins, but reduced EGF-stimulated binding proteins to 36-40 kDa. Similarly, tunicamycin treatment, which inhibits glycosylation, reduced only the size of this larger binding protein species. Polyclonal antisera directed against the human amniotic fluid binding protein (BP-28) immunoprecipitated the 32 kDa sheep thyroid binding protein seen on ligand blot and the cross-linked binding protein at 36-38 kDa. Antibody against the major human serum binding protein (BP-53) recognized only the larger EGF-stimulated binding proteins. In contrast to sheep thyroid cells, rat FRTL5 thyroid cells produced no detectable IGF-binding proteins. We conclude that the predominant binding proteins produced by sheep thyroid cells under standard culture conditions are non-glycosylated and immunoreact with antiserum directed against BP-28. EGF and phorbol esters stimulate production of larger glycosylated binding proteins

  5. Dangers of growth hormone therapy in critically ill patients.

    PubMed

    Ruokonen, E; Takala, J

    2000-07-01

    Prolonged stay of patients is the major challenge for modern intensive care because of its effects on morbidity and resource utilization. Severe trauma or infection are associated with the catabolic response, characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone (rhGH) has been applied during two decades as an experimental therapy for patients requiring parenteral nutrition and for those with respiratory failure. Administration of rhGH has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of rhGH (with doses 10-20 times higher than those used for replacement therapy) increases the mortality of critically ill patients. This excessive mortality in patients treated with rhGH was related to infections and development of multiple organ failure. Administration of high doses of rhGH to critically ill patients cannot thus be recommended.

  6. Growth hormone prevents the development of autoimmune diabetes

    PubMed Central

    Villares, Ricardo; Kakabadse, Dimitri; Juarranz, Yasmina; Gomariz, Rosa P.; Martínez-A, Carlos; Mellado, Mario

    2013-01-01

    Evidence supports a relationship between the neuroendocrine and the immune systems. Data from mice that overexpress or are deficient in growth hormone (GH) indicate that GH stimulates T and B-cell proliferation and Ig synthesis, and enhances maturation of myeloid progenitor cells. The effect of GH on autoimmune pathologies has nonetheless been little studied. Using a murine model of type 1 diabetes, a T-cell–mediated autoimmune disease characterized by immune cell infiltration of pancreatic islets and destruction of insulin-producing β-cells, we observed that sustained GH expression reduced prodromal disease symptoms and eliminated progression to overt diabetes. The effect involves several GH-mediated mechanisms; GH altered the cytokine environment, triggered anti-inflammatory macrophage (M2) polarization, maintained activity of the suppressor T-cell population, and limited Th17 cell plasticity. In addition, GH reduced apoptosis and/or increased the proliferative rate of β-cells. These results support a role for GH in immune response regulation and identify a unique target for therapeutic intervention in type 1 diabetes. PMID:24218587

  7. Episodic molecular evolution of pituitary growth hormone in Cetartiodactyla.

    PubMed

    Maniou, Zoitsa; Wallis, O Caryl; Wallis, Michael

    2004-06-01

    The sequence of growth hormone (GH) is generally strongly conserved in mammals, but episodes of rapid change occurred during the evolution of primates and artiodactyls, when the rate of GH evolution apparently increased substantially. As a result the sequences of higher primate and ruminant GHs differ markedly from sequences of other mammalian GHs. In order to increase knowledge of GH evolution in Cetartiodactyla (Artiodactyla plus Cetacea) we have cloned and characterized GH genes from camel (Camelus dromedarius), hippopotamus (Hippopotamus amphibius), and giraffe (Giraffa camelopardalis), using genomic DNA and a polymerase chain reaction technique. As in other mammals, these GH genes comprise five exons and four introns. Two very similar GH gene sequences (encoding identical proteins) were found in each of hippopotamus and giraffe. The deduced sequence for the mature hippopotamus GH is identical to that of dolphin, in accord with current ideas of a close relationship between Cetacea and Hippopotamidae. The sequence of camel GH is identical to that reported previously for alpaca GH. The sequence of giraffe GH is very similar to that of other ruminants but differs from that of nonruminant cetartiodactyls at about 18 residues. The results demonstrate that the apparent burst of rapid evolution of GH occurred largely after the separation of the line leading to ruminants from other cetartiodactyls. PMID:15461431

  8. Mouse cellular cementum is highly dependent on growth hormone status.

    PubMed

    Smid, J R; Rowland, J E; Young, W G; Daley, T J; Coschigano, K T; Kopchick, J J; Waters, M J

    2004-01-01

    Cementum is known to be growth-hormone (GH)-responsive, but to what extent is unclear. This study examines the effects of extremes of GH status on cementogenesis in three lines of genetically modified mice; GH excess (giant), GH antagonist excess (dwarf), and GH receptor-deleted (GHR-KO) (dwarf). Age-matched mandibular molar tissues were processed for light microscope histology. Digital images of sections of first molar teeth were captured for morphometric analysis of lingual root cementum. Cross-sectional area of the cellular cementum was a sensitive guide to GH status, being reduced nearly 10-fold in GHR-KO mice, three-fold in GH antagonist mice, and increased almost two-fold in giant mice (p < 0.001). Cellular cementum length was similarly influenced by GH status, but to a lesser extent. Acellular cementum was generally unaffected. This study reveals cellular cementum to be a highly responsive GH target tissue, which may have therapeutic applications in assisting regeneration of the periodontium. PMID:14691110

  9. Gender Bias in U.S. Pediatric Growth Hormone Treatment.

    PubMed

    Grimberg, Adda; Huerta-Saenz, Lina; Grundmeier, Robert; Ramos, Mark Jason; Pati, Susmita; Cucchiara, Andrew J; Stallings, Virginia A

    2015-06-09

    Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <-2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <-2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5-20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <-2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <-2.25 SD. No gender differences in prevalence of height <-2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <-2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients.

  10. Cell transfection as a tool to study growth hormone action

    SciTech Connect

    Norstedt, G.; Enberg, B.; Francis, S.

    1994-12-31

    The isolation of growth hormone receptor (GHR) cDNA clones has made possible the transfection of GHRs into cultured cells. Our aim in this minireview is to show how the application of such approaches have benefited GHR research. GH stimulation of cells expressing GHR cDNAs can cause an alteration of cellular function that mimic those of the endogenous GHR. GHR cDNA transfected cells also offer a system where the mechanism of GH action can be studied. Such a system has been used to demonstrate that the GHR itself becomes tyrosine phosphorylated and that further phosphorylation of downstream proteins is important in GH action. The GH signals are transmitted to the nucleus and GH regulated genes have now begun to be characterized. The ability to use cell transfection for mechanistic studies of GH action will be instrumental to define domains within the receptor that are of functional importance and to determined pathways whereby GH signals are conveyed within the cell. 33 refs., 2 tabs.

  11. Stability of human growth hormone in supercritical carbon dioxide.

    PubMed

    Kelly, Catherine A; Howdle, Steven M; Naylor, Andrew; Coxhill, Graham; Tye, Laura C; Illum, Lisbeth; Lewis, Andrew L

    2012-01-01

    The instability of human growth hormone (hGH) to temperature and interfaces makes its formulation into injectable, sustained-release drug delivery systems challenging. A novel method of encapsulating hGH in polymeric microparticles has been developed using supercritical CO(2) (scCO(2)) technology, but there is limited understanding of the stability of hGH within this system. The aim of this study was to evaluate the stability of hGH in scCO(2) processing. The integrity of the protein was assessed following exposure to scCO(2) using a range of different analytical techniques. Mass spectrometry showed that no peptide cleavage occurred as a result of processing or exposure to scCO(2). Size-exclusion chromatography detected formation of aggregates at high temperatures, but not as a result of the encapsulation process. Reverse-phase chromatography demonstrated that the production of deamidation products occurred as a function of temperature, but only at temperatures higher than those used for the encapsulation process. Circular dichroism and infrared spectroscopy demonstrated that the use of scCO(2) was not detrimental to the secondary molecular structure of hGH. Together, these results show that the structural integrity of hGH is unaffected by scCO(2) processing and that hGH can be successfully encapsulated in polymer microparticles using this technique.

  12. Exceptional Association Between Klinefelter Syndrome and Growth Hormone Deficiency

    PubMed Central

    Doubi, Sana; Amrani, Zoubida; Ouahabi, Hanan El; Boujraf, Saïd; Ajdi, Farida

    2015-01-01

    Klinefelter syndrome (KS) is characterized in adults by the combination of a tall stature, small testes, gynecomastia, and azoospermia. This case is described in a North African population of the Mediterranean region of North Africa. We report the case of a male 16 years old, of Arab ethnic origin, and diagnosed with this syndrome, who had a small height in relation to a growth hormone (GH) deficiency and a history of absence seizures (generalized myoclonic epilepsy). The patient's size was <−2.8 standard deviation (SD) with weight <−3 SD. GH deficiency was isolated and confirmed by two dynamic tests (insulin — hypoglycemia tolerance test and clonidine) with normal hypothalamic magnetic resonance imaging (MRI). GH supplementation using recombinant GH was advocated, while gonadotropin treatment was deferred. Small size in children or adolescents should not eliminate the diagnosis of Klinefelter syndrome — on the contrary, the presence of any associated sign (brain maturation, delay in puberty, aggressiveness) should encourage one to request a karyotype for the diagnosis and appropriate care of any case of KS that can be associated with GH deficiency, or which is in a variant form (isochromosome Xq, 49,XXXXY). PMID:27330737

  13. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.

    PubMed

    Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O; Diaz-Ruiz, Alberto; Frank, Stuart J; Manzano, Anna; Bartrons, Ramon; Puchowicz, Michelle; Kopchick, John J; Kineman, Rhonda D

    2015-09-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. PMID:26015548

  14. Dissolving Microneedle Patch for Transdermal Delivery of Human Growth Hormone

    PubMed Central

    Lee, Jeong Woo; Choi, Seong-O; Felner, Eric I.

    2014-01-01

    Clinical impact of biotechnology has been constrained by the limitations of traditional hypodermic injection of biopharmaceuticals. Microneedle patches have been proposed as a minimally invasive alternative. In this study, we assess the translation of a dissolving microneedle patch designed for simple, painless self-administration of biopharmacetucials that generates no sharp biohazardous waste. To study pharmacokinetics and safety of this approach, human growth hormone (hGH) was encapsulated in 600 μm long dissolving microneedles composed of carboxymethylcellulose and trehalose using an aqueous, moderate-temperature process that maintained complete hGH activity after encapsulation and retained most activity after storage for up to 15 months at room temperature and humidity. After manual insertion into the skin of hairless rats, hGH pharmacokinetics were similar to conventional subcutaneous injection. After patch removal, the microneedles had almost completely dissolved, leaving behind only blunt stubs. The dissolving microneedle patch was well tolerated, causing only slight, transient erythema. This study suggests that a dissolving microneedle patch can deliver hGH and other biopharmaceuticals in a manner suitable for self-administration without sharp biohazardous waste. PMID:21360810

  15. The effect of chronic ethanol ingestion on growth hormone secretion and hepatic sexual dimorphism in male rats

    SciTech Connect

    Lechner, P.S.

    1992-01-01

    The effect of chronic ethanol ingestion on the activities of several sexually dimorphic hepatic proteins was investigated in male rats by feeding a nutritionally adequate liquid diet supplemented with either ethanol or dextrimaltose. Two androgen-responsive proteins served as markers of masculine hepatic function. A high capacity, moderate affinity male estrogen-binding protein (MEB) is found only in male rat liver cytosol and this activity was significantly reduced in all animals consuming ethanol at a dose of 5% by volume. The estrogen metabolizing enzyme estrogen 2-hydroxylase was also significantly reduced in male rats fed ethanol. Two proteins having higher activity in female compared to male liver were chosen as indicators of feminization: ceruloplasmin and 5[alpha]-reductase. Ceruloplasmin activity was increased after long term feeding of ethanol, but not after shorter durations of alcohol consumption. The 5a-reductase activity was not significantly affected by any of the alcohol feeding studies. Serum testosterone levels were not significantly decreased after ethanol consumption. After 30 or 60 days of ethanol ingestion, serum estradiol was elevated 34% and 40%. The reversibility of ethanol effects was determined by a gradual withdrawal of alcohol from the diet. The effect of ethanol consumption on sex-specific patterns of growth hormone secretion was examined. The secretory pattern of alcohol-fed rats was not feminized; after ethanol ingestion, the frequency of growth hormone pulses was unchanged. An increase in pulse height and mean growth hormone concentration was observed after 60 days of ethanol consumption. This results constitutes a change away from rather than toward the characteristics of a female secretory pattern. The feminization of activities of the male estrogen binding protein and of estrogen 2-hydroxylase in male rat liver after chronic ethanol consumption are not apparently related to a feminization of growth hormone secretion pattern.

  16. Growth hormone and risk for cardiac tumors in Carney complex.

    PubMed

    Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A

    2016-09-01

    Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor.

  17. Growth hormone and risk for cardiac tumors in Carney complex.

    PubMed

    Bandettini, W Patricia; Karageorgiadis, Alexander S; Sinaii, Ninet; Rosing, Douglas R; Sachdev, Vandana; Schernthaner-Reiter, Marie Helene; Gourgari, Evgenia; Papadakis, Georgios Z; Keil, Meg F; Lyssikatos, Charalampos; Carney, J Aidan; Arai, Andrew E; Lodish, Maya; Stratakis, Constantine A

    2016-09-01

    Carney complex (CNC) is a multiple neoplasia syndrome that is caused mostly by PRKAR1A mutations. Cardiac myxomas are the leading cause of mortality in CNC patients who, in addition, often develop growth hormone (GH) excess. We studied patients with CNC, who were observed for over a period of 20 years (1995-2015) for the development of both GH excess and cardiac myxomas. GH secretion was evaluated by standard testing; dedicated cardiovascular imaging was used to detect cardiac abnormalities. Four excised cardiac myxomas were tested for the expression of insulin-like growth factor-1 (IGF-1). A total of 99 CNC patients (97 with a PRKAR1A mutation) were included in the study with a mean age of 25.8 ± 16.6 years at presentation. Over an observed mean follow-up of 25.8 years, 60% of patients with GH excess (n = 46) developed a cardiac myxoma compared with only 36% of those without GH excess (n = 54) (P = 0.016). Overall, patients with GH excess were also more likely to have a tumor vs those with normal GH secretion (OR: 2.78, 95% CI: 1.23-6.29; P = 0.014). IGF-1 mRNA and protein were higher in CNC myxomas than in normal heart tissue. We conclude that the development of cardiac myxomas in CNC may be associated with increased GH secretion, in a manner analogous to the association between fibrous dysplasia and GH excess in McCune-Albright syndrome, a condition similar to CNC. We speculate that treatment of GH excess in patients with CNC may reduce the likelihood of cardiac myxoma formation and/or recurrence of this tumor. PMID:27535175

  18. Further studies on phosphorylated pituitary somatotropin (growth hormone)

    SciTech Connect

    Kornberg, L.J.; Liberti, J.P.

    1987-05-01

    This laboratory made the original observation that naturally-occurring ovine growth hormone (GH) is phosphorylated and that slices of pituitary glands from male rats synthesize and secrete /sup 32/P-GH. This observation has been extended to explore the generality of this process. After incubation in PO/sub 4/-free Ham's F-10 medium (PFH) or in saline/Hepes (SH) containing 300..mu..Ci /sup 32/Pi/mL, tissue and medium were separated and a cell extract was prepared. GH in the medium and extract was recovered by immunoprecipitation using rat GH antiserum. The samples were electrophoresed under denaturating conditions and processed for autoradiography. /sup 32/P-GH was characterized by the presence of a protein-staining band and radioactive area which migrated the same as authentic GH and /sup 125/I-GH. Slices of glands from male rats incubated for 2h in PFH secreted /sup 32/P-GH. Similar results were found upon incubation of slices from female rats in the presence of SH. Short-term incubations of acutely dispersed pituitary cells obtained from young and old male rats also synthesized and secreted /sup 32/P-GH. Thus, the production of /sup 32/P-GH occurs (a) in simple and complex incubaton media, (b) in slices and cells from glands from older and younger rats and (c) in female as well as male rats. Therefore, phosphorylation of GH appears to be a general phenomenon. The physiological action(s) of phosphorylated GH in growth and development is under study.

  19. [Transthyretin-binding activity of hexabromocyclododecanes (HBCDs) and its thyroid hormone disrupting effects after developmental exposure].

    PubMed

    Ji, Xiu-Ling; Liu, Yang; Liu, Fang; Lu, Yue; Zhong, Gao-Ren

    2010-09-01

    In vivo and in vitro research approaches were carried out to survey the potential health risk of environmental exposure by hexabromocyclododecanes (HBCDs). Transthyretin-binding assay was designed to test for the potency of HBCDs to compete with thyroxine (T4) for binding to the transport protein. The results showed that the binding of 25I-T4 and T4 was only slightly inhabited even at the highest competitive concentration of HBCDs (75.08%, 80 micromol x L(-1)), indicating the marginally interfere potency of HBCDs in the transportation of T4. Sprague-Dawley rats of 3-days old were exposed to 0.2 mg/kg and 1 mg/kg HBCDs for 21 d to examine the thyroid hormones (THs) disrupting effects of HBCDs after developmental exposure. Compared with the controls, levels of total 3,3',5-triiodothyronine (TT3), free 3,3',5-triiodothyronine (FT3), increased significantly (p < 0.05, p < 0.05) in low- and high-dose exposures, thyroid stimulating hormone (TSH) also increased slightly while the total thyroxine (TT4), free thyroxine (FT4) had a decline about two-fold inversely. Combined both the in vivo and in vitro results, the possible mode of action of HBCDs on THs disruption may through the synergy or substitution effect of T3. The findings support further investigation of the potential THs disrupting effects of HBCDs on public health, especially on children during brain development. PMID:21072945

  20. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

    PubMed

    Chang, Chung-Hsun; Tsai, Wen-Chung; Hsu, Ya-Hui; Pang, Jong-Hwei Su

    2014-01-01

    BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon. PMID:25415472

  1. Diacylglycerol production induced by growth hormone in Ob1771 preadipocytes arises from phosphatidylcholine breakdown

    SciTech Connect

    Catalioto, R.M.; Ailhaud, G.; Negrel, R. )

    1990-12-31

    Growth Hormone has recently been shown to stimulate the formation of diacylglycerol in Ob1771 mouse preadipocyte cells without increasing inositol lipid turnover. Addition of growth hormone to Ob1771 cells prelabelled with ({sup 3}H)glycerol or ({sup 3}H)choline led to a rapid, transient and stoechiometric formation of labelled diacylglycerol and phosphocholine, respectively. In contrast, no change was observed in the level of choline and phosphatidic acid whereas the release of water-soluble metabolites in ({sup 3}H)ethanolamine prelabelled cells exposed to growth hormone was hardly detectable. Stimulation by growth hormone of cells prelabelled with (2-palmitoyl 9, 10 ({sup 3}H))phosphatidylcholine also induced the production of labelled diacyglycerol. Pertussis toxin abolished both diacylglycerol and phosphocholine formation induced by growth hormone. It is concluded that growth hormone mediates diacylglycerol production in Ob1771 cells by means of phosphatidylcholine breakdown involving a phospholipase C which is likely coupled to the growth hormone receptor via a pertussis toxin-sensitive G-protein.

  2. Characterization of striped bass growth hormone receptors by disulfide-bond reduction and cross-linking studies.

    PubMed

    Gray, E S; Tsai, R W

    1994-05-01

    Growth hormone (GH) receptors were analyzed in striped bass (Morone saxatilis) by addition of disulfide-bond reducing agents to radioreceptor assays and by cross-linking both striped bass and coho salmon (Oncorhynchus kisutch) crude membrane preparations to radiolabeled hormone. Dithiothreitol (DTT) caused a dose-dependent increase in specific binding of 125I-tilapia (Oreochromis mossambicus) GH to striped bass membrane preparations. Maximal enhancement of 3.4-fold was obtained with 1 mM DTT and 0.03 trypsin inhibitor units/ml of aprotinin. Addition of N-ethylmaleimide (NEM), which binds covalently to free sulfhydryl groups, decreased specific binding. Scatchard analysis of striped bass membrane preparations indicated a single class of GH receptors. Addition of DTT with aprotinin increased GH-binding site concentration from 278 to 507 fmol/mg, while the dissociation constant of 0.56 nM remained unchanged. Cross-linking 125I-tilapia GH to striped bass hepatic membrane preparations and 125I-salmon GH to coho salmon membrane preparations yielded two to three specifically labeled proteins on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Endoglycosidase H treatment was without effect on specifically labeled proteins from either species. Following digestion with N-glycosidase F, relative molecular weights of specifically labeled 125I-GH complexes were reduced, suggesting that hepatic GH-binding proteins in striped bass and salmon are N-linked glycoproteins.

  3. The relationship between growth hormone polymorphism and growth hormone receptor genes with milk yield and reproductive performance in Holstein dairy cows

    PubMed Central

    Hadi, Z; Atashi, H; Dadpasand, M; Derakhshandeh, A; Ghahramani Seno, M. M

    2015-01-01

    The aim of this study was to investigate the potential association between growth hormone GH/AluI and growth hormone receptor GHR/AluI polymorphisms with milk yield and reproductive performances in Holstein dairy cows in Iran. Blood samples of 150 Holstein cows were collected and their genomic DNA was extracted using Gene-Fanavaran DNA extracting kit. Fragments of the 428 bp of exon 5 growth hormone (GH) gene and the 342 bp of exon 10 growth hormone receptor (GHR) gene were amplified using the polymerase chain reaction (PCR) method. PCR products were digested by the AluI restriction enzyme and electrophoresed on 3% agarose gel. Continuous and categorical data were analyzed using linear mixed models through Proc MIXED and logistic regression models through Proc GENMOD of SAS software, respectively. The results showed no relationship between the examined traits and GH/AluI or GHR/AluI genes. A significant relationship was found between GH/AluI polymorphism and dystocia, but the presence of the GH-L allele reduced the incidence of dystocia. The results suggest that the GH-LL genotype reduces dystocia probably by affecting the release of growth hormone; nevertheless, further studies will be needed to examine the relationship between dystocia and GH genotypes. PMID:27175183

  4. Intimate associations between the endogenous opiate systems and the growth hormone-releasing hormone system in the human hypothalamus.

    PubMed

    Olsen, J; Peroski, M; Kiczek, M; Grignol, G; Merchenthaler, I; Dudas, B

    2014-01-31

    Although it is a general consensus that opioids modulate growth, the mechanism of this phenomenon is largely unknown. Since endogenous opiates use the same receptor family as morphine, these peptides may be one of the key regulators of growth in humans by impacting growth hormone (GH) secretion, either directly, or indirectly, via growth hormone-releasing hormone (GHRH) release. However, the exact mechanism of this regulation has not been elucidated yet. In the present study we identified close juxtapositions between the enkephalinergic/endorphinergic/dynorphinergic axonal varicosities and GHRH-immunoreactive (IR) perikarya in the human hypothalamus. Due to the long post mortem period electron microscopy could not be utilized to detect the presence of synapses between the enkephalinergic/endorphinergic/dynorphinergic and GHRH neurons. Therefore, we used light microscopic double-label immunocytochemistry to identify putative juxtapositions between these systems. Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with enkephalinergic axonal varicosities in the infundibular nucleus/median eminence, while endorphinergic-GHRH juxtapositions were much less frequent. In contrast, no significant dynorphinergic-GHRH associations were detected. The density of the abutting enkephalinergic fibers on the surface of the GHRH perikarya suggests that these juxtapositions may be functional synapses and may represent the morphological substrate of the impact of enkephalin on growth. The small number of GHRH neurons innervated by the endorphin and dynorphin systems indicates significant differences between the regulatory roles of endogenous opiates on growth in humans. PMID:24239719

  5. [Effect of growth hormone and calcitriol on the growth plate in uremic rats].

    PubMed

    Amil, B; Fernández-Fuente, M; Santos, F; Rodríguez, J; Díaz-Tejón, L; García, E; Carbajo, E

    2003-01-01

    This study analyzed the modifications induced by growth hormone (GH) and/or calcitriol treatments in the growth plate of growth retarded uremic rats. Four groups of 5/6 nephrectomized rats were studied: untreated (U), treated with GH (U + GH), treated with calcitriol (U + D), treated with GH and calcitriol (U + GH + D). Treatments were given intraperitoneally during the second week of renal failure. Uremic groups were compared with sham-operated rats fed ad libitum (C) or pair-fed with U (CP). In comparison with C and CP, histomorphometric analysis of tibial proximal ends of U group showed decreased bone formation, as estimated by osseous front advance (OFA), elongation of growth cartilage and its hypertrophic zone, and decreased size of most distal chondrocytes. The U + D group tended to normalize growth cartilage height, and that of its hypertrophic zone, as well as the size of chondrocytes. In U + GH group OFA improved and chondrocyte size became normal, but growth cartilage remained elongated. Similar results were found in the U + GH + D group. These findings indicate that, in chronic renal insufficiency, the beneficial effect of GH on growth is not associated with normalization of growth cartilage morphology and that calcitriol facilitates chondrocyte maturation. When given together the effect of GH prevails.

  6. Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting

    SciTech Connect

    Perret-Vivancos, Cecile; Abbate, Aude; Ardail, Dominique; Raccurt, Mireille; Usson, Yves; Lobie, Peter E.; Morel, Gerard . E-mail: gerard.morel@univ-lyon1.fr

    2006-02-01

    Growth hormone (GH) binding to its receptor (GHR) initiates GH-dependent signal transduction and internalization pathways to generate the biological effects. The precise role and way of action of GH on mitochondrial function are not yet fully understood. We show here that GH can stimulate cellular oxygen consumption in CHO cells transfected with cDNA coding for the full-length GHR. By using different GHR cDNA constructs, we succeeded in determining the different parts of the GHR implicated in the mitochondrial response to GH. Polarography and two-photon excitation fluorescence microscopy analysis showed that the Box 1 of the GHR intracellular domain was required for an activation of the mitochondrial respiration in response to a GH exposure. However, confocal laser scanning microscopy demonstrated that cells lacking the GHR Box 1 could efficiently internalize the hormone. We demonstrated that internalization mediated either by clathrin-coated pits or by caveolae was able to regulate GH mitochondrial effect: these two pathways are both essential to obtain the GH stimulatory action on mitochondrial function. Moreover, electron microscopic and biochemical approaches allowed us to identify the caveolar pathway as essential for targeting GH and GHR to mitochondria.

  7. Effects of long-term growth hormone-releasing factor administration on plasma growth hormone, luteinizing hormone and progesterone profiles in growing female buffaloes (Bubalus bubalis).

    PubMed

    Mondal, M; Prakash, B S

    2004-10-01

    To investigate the effects of long-term growth hormone-releasing factor (GRF) administration on plasma growth hormone (GH), LH and progesterone and body weight gain in growing buffalo calves, 12 female Murrah buffaloes within the age group of 6-8 months of age were divided into two groups (treatment and control groups) of six each in such a way so that average body weights between the groups did not differ (p > 0.05). Control buffaloes were not given any hormonal treatment and treatment group buffaloes were treated with synthetic bovine GRF [bGRF (1-44)-NH(2)] at the rate of 10 microg/100 kg body weight intravenously at an interval of 15 days from week 6 (5-week pre-treatment period) till 18 injections were completed (week 6-42 treatment period) and thereafter, effect of exogenous GRF were observed for 10-week post-treatment period. Jugular blood samples were drawn twice a week at 3-4-day intervals for plasma GH, LH and progesterone quantification. Body weight of all animals was recorded twice a week. During pre-treatment period, mean plasma GH, LH and progesterone did not differ (p > 0.05) between the groups. But during treatment as well as post-treatment period, mean plasma GH levels were found to be significantly (p < 0.01) higher in treatment than control group of buffaloes. Administration of GRF for longer term sustained a higher level of plasma GH even after cessation of treatment. GRF-treated buffaloes attained higher (p < 0.01) body weight than the controls. Repeated GRF administration for long-term significantly (p < 0.01) increased plasma LH and progesterone. In conclusion, repeated long-term exogenous GRF administration induces and even enhances GH release without any sign of refractoriness. GRF may, therefore, be used to induce daily GH release without loss of responsiveness over an extended period of time in young growing female buffaloes and it may assist these animals to grow faster. PMID:15367266

  8. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release.

    PubMed

    Zhou, Aiwu; Wei, Zhenquan; Stanley, Peter L D; Read, Randy J; Stein, Penelope E; Carrell, Robin W

    2008-06-27

    Corticosteroids are transported in the blood by a serpin, corticosteroid-binding globulin (CBG), and their normally equilibrated release can be further triggered by the cleavage of the reactive loop of CBG. We report here the crystal structures of cleaved human CBG (cCBG) at 1.8-A resolution and its complex with cortisol at 2.3-A resolution. As expected, on cleavage, CBG undergoes the irreversible S-to-R serpin transition, with the cleaved reactive loops being fully incorporated into the central beta-sheet. A connecting loop of helix D, which is in a helix-like conformation in native CBG, unwinds and grossly perturbs the hormone binding site following beta-sheet expansion in the cCBG structure but shifts away from the binding site by more than 8 A following the binding of cortisol. Unexpectedly, on cortisol binding, the hormone binding site of cCBG adopts a configuration almost identical with that of the native conformer. We conclude that CBG has adapted an allosteric mechanism of the serpins to allow equilibrated release of the hormones by a flip-flop movement of the intact reactive loop into and out of the beta-sheet. The change in the hormone binding affinity results from a change in the flexibility or plasticity of the connecting loop, which modulates the configuration of the binding site.

  9. Radiometric immunosorbent assay for the detection of anti-hormone-binding protein antibodies

    SciTech Connect

    Pierce, E.A.; Dame, M.C.; DeLuca, H.F.

    1986-02-15

    A radiometric immunosorbent assay (RISA) for the detection of monoclonal antibodies to hormone-binding proteins has been developed. The assay involves incubating hybridoma supernatants in microtiter wells that have been coated with goat anti-mouse IgG antibodies. Any mouse IgG in the test supernatant is thus specifically retained in the wells. Radioactive ligand-binding protein complexes are then incubated in the wells. The presence of anti-binding protein antibodies in the supernatant is indicated by specific retention of radioactive ligand-binding protein complexes in the wells. Crude antigen preparations, such as tissue homogenates, can be used to detect antibodies. The assay is capable of detecting antibody at concentrations 20 ng/ml (approx. 100 pM IgG). The RISA has been used successfully to screen for monoclonal antibodies to the intracellular receptor for 1,25-dihydroxyvitamin D/sub 3/ and should be useful for the detection of antibodies to ligand-binding proteins in general.

  10. Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

    USGS Publications Warehouse

    Lerner, Darren T.; Sheridan, Mark A.; McCormick, Stephen D.

    2012-01-01

    Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 μg g−1 17β-estradiol (E2) or 150 μg g−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 μg g−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

  11. Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice.

    PubMed

    Li, Yuesheng; Knapp, Joanne R; Kopchick, John J

    2003-02-01

    Growth hormone (GH) acts on adipose tissue by accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization. To investigate whether GH is involved in the development and metabolism of interscapular brown adipose tissue (BAT), a site of nonshivering thermogenesis, we employed three lines of transgenic mice. Two of the lines are dwarf due to expression of a GH antagonist (GHA) or disruption of the GH receptor/binding-protein gene. A third mouse line is giant due to overexpression of a bovine GH (bGH) transgene. We have found that the body weights of those animals are proportional to their body lengths at 10 weeks of age. However, GHA dwarf mice tend to catch up with the nontransgenic (NT) littermates in body weight but not in body length at 52 weeks of age. The increase of body mass index (BMI) for GHA mice accelerates rapidly relative to controls as a function of age. We have also observed that BAT in both dwarf mouse lines but not in giant mice is enlarged in contrast to nontransgenic littermates. This enlargement occurs as a function of age. Northern analysis suggests that BAT can be a GH-responsive tissue because GHR/BP mRNAs were found there. Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT.

  12. MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells.

    PubMed

    Lee, G J; Jun, J W; Hyun, S

    2015-06-01

    Metabolic organs such as the liver and adipose tissue produce several peptide hormones that influence metabolic homeostasis. Fat bodies, the Drosophila counterpart of liver and adipose tissues, have been thought to analogously secrete several hormones that affect organismal physiology, but their identity and regulation remain poorly understood. Previous studies have indicated that microRNA miR-8, functions in the fat body to non-autonomously regulate organismal growth, suggesting that fat body-derived humoral factors are regulated by miR-8. Here, we found that several putative peptide hormones known to have mitogenic effects are regulated by miR-8 in the fat body. Most members of the imaginal disc growth factors and two members of the adenosine deaminase-related growth factors are up-regulated in the absence of miR-8. Drosophila insulin-like peptide 6 (Dilp6) and imaginal morphogenesis protein-late 2 (Imp-L2), a binding partner of Dilp, are also up-regulated in the fat body of miR-8 null mutant larvae. The fat body-specific reintroduction of miR-8 into the miR-8 null mutants revealed six peptides that showed fat-body organ-autonomous regulation by miR-8. Amongst them, only Imp-L2 was found to be regulated by U-shaped, the miR-8 target for body growth. However, a rescue experiment by knockdown of Imp-L2 indicated that Imp-L2 alone does not account for miR-8's control over the insect's growth. Our findings suggest that multiple peptide hormones regulated by miR-8 in the fat body may collectively contribute to Drosophila growth.

  13. Synthesis of the Growth Hormone Secretion Mechanism Using Nonlinear Analysis and CAD Tools.

    PubMed

    Shell, J R

    2005-01-01

    The goal of this paper is to present a hardware realization of the feed-forward and feedback hypothalamic-pituitary growth hormone (GH) secretion mechanism based on a bio-mathematical nonlinear delay differential equation model developed by Farhy et al. (2003) and Veldhuis et al. (2001). Behavioral modeling is implemented through Verilog hardware descriptive language (HDL) to simulate the antagonistic and stimulatory interaction of growth hormone, growth hormone releasing hormone (GHRH) and somatotropin release inhibiting factor (SRIF). The model is synthesized using computer aided design (CAD) tools and is promulgated through a combinational complex programmable logic device (CPLD)/field programmable grid array (FPGA) Xilinx XSA-50 microchip. The microchip sequentially displays the decimal equivalents of the time changing hormonal concentration levels of the biomathematical model.

  14. Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone

    PubMed Central

    Melia, Tisha; Hao, Pengying; Yilmaz, Feyza

    2015-01-01

    Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as key chromatin regulators, yet few studies have characterized lincRNAs in a single tissue under diverse conditions. Here, we analyzed 45 mouse liver RNA sequencing (RNA-Seq) data sets collected under diverse conditions to systematically characterize 4,961 liver lincRNAs, 59% of them novel, with regard to gene structures, species conservation, chromatin accessibility, transcription factor binding, and epigenetic states. To investigate the potential for functionality, we focused on the responses of the liver lincRNAs to growth hormone stimulation, which imparts clinically relevant sex differences to hepatic metabolism and liver disease susceptibility. Sex-biased expression characterized 247 liver lincRNAs, with many being nuclear RNA enriched and regulated by growth hormone. The sex-biased lincRNA genes are enriched for nearby and correspondingly sex-biased accessible chromatin regions, as well as sex-biased binding sites for growth hormone-regulated transcriptional activators (STAT5, hepatocyte nuclear factor 6 [HNF6], FOXA1, and FOXA2) and transcriptional repressors (CUX2 and BCL6). Repression of female-specific lincRNAs in male liver, but not that of male-specific lincRNAs in female liver, was associated with enrichment of H3K27me3-associated inactive states and poised (bivalent) enhancer states. Strikingly, we found that liver-specific lincRNA gene promoters are more highly species conserved and have a significantly higher frequency of proximal binding by liver transcription factors than liver-specific protein-coding gene promoters. Orthologs for many liver lincRNAs were identified in one or more supraprimates, including two rat lincRNAs showing the same growth hormone-regulated, sex-biased expression as their mouse counterparts. This integrative analysis of liver lincRNA chromatin states, transcription factor occupancy, and growth hormone regulation provides novel insights into the

  15. Functional binding of a vertebrate hormone, L-3,5,3'-triiodothyronine (T3), on insect follicle cell membranes.

    PubMed

    Kim, Y; Davari, E D; Sevala, V; Davey, K G

    1999-10-01

    A vertebrate hormone, L-3,5,3'-triiodothyronine (T3), induces volume reduction in the follicle cells of Locusta migratoria and Rhodnius prolixus. The effect of T3 on locust follicle cells is inhibited by ouabain and by antibodies raised against a membrane binding protein for juvenile hormone (JH). [125I]-T3 binds to membrane preparations of vitellogenic follicles in a specific and saturable fashion, with a KD in the low nanomolar range. T3 and JH III exhibited equivalent abilities to compete for the T3 binding site. These findings strongly suggest that T3 and JH act via the same receptor in follicle cells. PMID:10528413

  16. Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.

    PubMed

    Alamino, Vanina A; Mascanfroni, Iván D; Montesinos, María M; Gigena, Nicolás; Donadio, Ana C; Blidner, Ada G; Milotich, Sonia I; Cheng, Sheue-Yann; Masini-Repiso, Ana M; Rabinovich, Gabriel A; Pellizas, Claudia G

    2015-04-01

    Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy.

  17. Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency

    PubMed Central

    Mitchell, H; Dattani, M; Nanduri, V; Hindmarsh, P; Preece, M; Brook, C

    1999-01-01

    BACKGROUND—Growth hormone insufficiency (GHI) is diagnosed conventionally by short stature and slow growth, and is confirmed by diminished peak GH response to a provocation test. Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) have previously been considered individually
OBJECTIVE—To test the hypothesis that the combined analysis of IGF-I and IGFBP-3 could act as a surrogate marker for the diagnosis of GHI.
DESIGN—Reference ranges for IGF-I and IGFBP-3 were calculated using 521 normal individuals. A retrospective analysis was performed on 318 children referred for investigation of short stature.
RESULTS—No significant difference was found between either the IGF-I or IGFBP-3 standard deviation scores (SDSs) in children with and without GHI. If the requirement were for both tests to be positive (< −2 SDS) for a diagnosis of GHI, then 99% of children without GHI would be correctly identified; however, the sensitivity of the test was only 15%.
CONCLUSIONS—Neither IGF-I nor IGFBP-3 alone is a marker for GHI. In addition, they cannot be used as an effective screening test in combination.

 PMID:10208950

  18. Defining the epigenetic actions of growth hormone: acute chromatin changes accompany GH-activated gene transcription.

    PubMed

    Chia, Dennis J; Rotwein, Peter

    2010-10-01

    Many of the long-term physiological effects of GH require hormone-mediated changes in gene expression. The transcription factor signal transducer and activator of transcription 5b (Stat5b) plays a critical role in the actions of GH on growth and metabolism by regulating a large number of GH-dependent genes by incompletely understood mechanisms. Here we have assessed the impact of GH-initiated and Stat5b-mediated signaling on the chromatin landscape of hormone-regulated genes in the liver of pituitary-deficient young adult male rats. In the absence of GH there was minimal ongoing transcription at the Socs2, Cish, Igfals, and Spi 2.1 promoters, minimal occupancy of Stat5b at proximal promoter sites, and relatively closed chromatin, as evidenced by low levels of core histone acetylation. In contrast, transcriptionally silent Igf1 promoter 1 appeared poised to be activated, based on binding of coactivators p300 and Med1/Trap220, high levels of histone acetylation, and the presence of RNA polymerase II. GH treatment led to a 8- to 20-fold rise in transcriptional activity of all five genes within 30-60 min and was accompanied by binding of Stat5b to the proximal Socs2, Cish, Igfals, and Spi 2.1 promoters and to seven distal Igf1 Stat5b elements, by enhanced histone acetylation at all five promoters, by recruitment of RNA polymerase II to the Socs2, Cish, Igfals, and Spi 2.1 promoters, and by loss of the transcriptional repressor Bcl6 from Socs2, Cish, and Igfals Stat5b sites, but not from two Igf1 Stat5b domains. We conclude that GH actions induce rapid and dramatic changes in hepatic chromatin at target promoters and propose that the chromatin signature of Igf1 differs from other GH-and Stat5b-dependent genes. PMID:20702579

  19. Oxidative stress impact on growth hormone secretion in the eye

    PubMed Central

    Šarić, Borna; Šarić, Vlatka Brzović; Barberić, Monika; Predović, Jurica; Rumenjak, Vlatko; Cerovski, Branimir

    2015-01-01

    Aim To evaluate the influence of oxidative stress on extrapituitary growth hormone (GH) secretion in the eye and to analyze the interdependence between eye and serum GH levels under normal and hypoxic conditions. Methods Pars plana vitrectomy (PPV) was performed in 32 patients with developed proliferative diabetic retinopathy (PDR) and 49 non-diabetic controls, both of whom required this procedure as part of their regular treatment in the period from April 2013 to December 2014. During PPV, vitreous samples were taken and blood was simultaneously collected from the cubital vein. GH levels in serum and vitreous samples were measured by electrochemical luminescence assay. Oxidative stress was measured by enzyme-linked immunosorbent assay of advanced oxidation protein products (AOPP) and lipid hydroperoxide (LPO) in serum and vitreous. Results Serum AOPP levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group) and LPO levels were significantly higher only in PDR group (P < 0.001). There was a significant positive correlation between serum and vitreous LPO levels in PDR group (r = 0.909; P < 0.001). Serum GH levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group). Serum GH levels were significantly higher in PDR group than in controls (P = 0.012). Vitreous GH values were slightly higher in PDR group, but the difference was not significant. Conclusion Our study confirms that GH production in the eye is autonomous and independent of oxidative stress or pituitary GH influence. PMID:26321025

  20. Responses of growth hormone aggregates to different intermittent exercise intensities.

    PubMed

    Rubin, Martyn R; Kraemer, William J; Kraemer, Robert R; Durand, Robert J; Acevedo, Edmund O; Johnson, Lisa G; Castracane, V D; Scheett, Timothy P; French, Duncan N; Volek, Jeff S

    2003-04-01

    The purpose of this study was to determine the impact of high-intensity intermittent exercise on the presence of circulating growth hormone (GH) aggregates measured using two different assay techniques. Six male subjects with endurance training background participated in this study under both exercise and no-exercise control conditions. After resting blood sampling, subjects completed an intermittent treadmill exercise protocol at four speeds predicted to elicit a specific VO(2):60% VO(2max) for 10 min, 75% for 10 min, 90% for 5 min, and 100% for 2 min. After each exercise intensity was completed treadmill speed was reduced to a walk (3.5-4 min) for blood sampling. Sampling continued every 15 min for 1 h into recovery. All samples were then measured for GH concentrations using Nichols immunoradiometric assay (IRMA) and Diagnostic Systems Laboratory's immunofunctional assay (IFA). A second set of samples was chemically reduced using reduced glutathione (GSH; 10 mM for 18 h at room temperature) to break disulfide bonds between possible oligomeric GH complexes, and subsequently assayed using the same GH assays. With the IRMA, GH was significantly elevated ( P<0.05) after the 75% workload and remained elevated through 30 min post-exercise. After adding GSH to the sample, the IRMA indicated significant increases in GH as early as the 60% exercise intensity and remained elevated through 45 min into recovery. At 75%, the GSH assay run was significantly higher than the non-GSH assay run. With the IFA, GH was significantly elevated at 60% in the non-GSH condition, whereas the GSH assay run indicated significant elevations at 75%. Both GSH and non-GSH conditions remained elevated through 30 min into recovery. These data indicate that the addition of GSH to serum samples prior to assay via an IRMA may break existing disulfide bonds between aggregated GH molecules, thus altering the apparent assay signal to reveal greater total GH in the sample.

  1. Gender Bias in U.S. Pediatric Growth Hormone Treatment

    PubMed Central

    Grimberg, Adda; Huerta-Saenz, Lina; Grundmeier, Robert; Ramos, Mark Jason; Pati, Susmita; Cucchiara, Andrew J.; Stallings, Virginia A.

    2015-01-01

    Growth hormone (GH) treatment of idiopathic short stature (ISS), defined as height <−2.25 standard deviations (SD), is approved by U.S. FDA. This study determined the gender-specific prevalence of height <−2.25 SD in a pediatric primary care population, and compared it to demographics of U.S. pediatric GH recipients. Data were extracted from health records of all patients age 0.5–20 years with ≥ 1 recorded height measurement in 28 regional primary care practices and from the four U.S. GH registries. Height <−2.25 SD was modeled by multivariable logistic regression against gender and other characteristics. Of the 189,280 subjects, 2073 (1.1%) had height <−2.25 SD. No gender differences in prevalence of height <−2.25 SD or distribution of height Z-scores were found. In contrast, males comprised 74% of GH recipients for ISS and 66% for all indications. Short stature was associated (P < 0.0001) with history of prematurity, race/ethnicity, age and Medicaid insurance, and inversely related (P < 0.0001) with BMI Z-score. In conclusion, males outnumbered females almost 3:1 for ISS and 2:1 for all indications in U.S. pediatric GH registries despite no gender difference in height <−2.25 SD in a large primary care population. Treatment and/or referral bias was the likely cause of male predominance among GH recipients. PMID:26057697

  2. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition.

    PubMed

    Reitz, M U; Gifford, M L; Schäfer, P

    2015-04-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth-immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth-immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth-immunity cross-talk.

  3. Multi-target QSAR and docking study of steroids binding to corticosteroid-binding globulin and sex hormone-binding globulin.

    PubMed

    Nikolic, Katarina; Filipic, Slavica; Agbaba, Danica

    2012-12-01

    The QSAR and docking studies were performed on fifty seven steroids with binding affinities for corticosteroid-binding globulin (CBG) and eighty four steroids with binding affinities for sex hormone-binding globulin (SHBG). Since the steroidal compounds have binding affinity for both CBG and SHBG, multi-target QSAR approach was employed to establish a unique QSAR method for simultaneous evaluation of the CBG and SHBG binding affinities. The constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Chem3D Ultra 7.0.0, the Dragon 6.0, the MOPAC2009, and the Chemical Descriptors Library (CDL) program. Partial least squares regression (PLSR) has been applied for selection of the most relevant molecular descriptors and QSAR models building. The QSAR (SHGB) model, QSAR model (CBG), and multi-target QSAR model (CBG, SHBG) were created. The multi-target QSAR model (CBG and SHBG) was found to be more effective in describing the CBG and SHBG affinity of steroids in comparison to the one target models (QSAR (SHGB) model, QSAR model (CBG)). The multi-target QSAR study indicated the importance of the electronic descriptor (Mor16v), steric/symmetry descriptors (Eig06_EA(ed)), 2D autocorrelation descriptor (GATS4m), distance distribution descriptor (RDF045m), and atom type fingerprint descriptor (CDL-ATFP 253) in describing the CBG and SHBG affinity of steroidal compounds. Results of the created multi-target QSAR model were in accordance with the performed docking studies. The theoretical study defined physicochemical, electronic and structural requirements for selective and effective binding of steroids to the CBG and SHBG active sites.

  4. Growth hormone (GH) activity is associated with increased serum oestradiol and reduced anti-Müllerian hormone in healthy male volunteers treated with GH and a GH antagonist.

    PubMed

    Andreassen, M; Frystyk, J; Faber, J; Kristensen, L Ø; Juul, A

    2013-07-01

    Growth hormone (GH) and insulin-like growth factor I (IGF-I) receptors are present on pituitary gonadotrophs and on testicular Leydig and Sertoli cells. Thus, the GH/IGF-I system may modulate the pituitary-gonadal axis in males. This is a randomized cross-over study. Eight healthy male volunteers (mean age 35, range 29-46 years) were treated with GH for 3 weeks (1st week 0.01, 2nd week 0.02, 3rd week 0.03 mg/day/kg) or a GH receptor antagonist (Pegvisomant) (1st week 10, last 2 weeks 15 mg/day), separated by 8 weeks of washout. Before and after the two treatment periods, concentrations of luteinizing hormone (LH), follicle-stimulating hormone, testosterone, oestradiol, sex hormone-binding globulin, inhibin B and Anti-Müllerian Hormone (AMH) were measured. During GH treatment, IGF-I increased [(median (IQR)] 166 (162-235) vs. 702 (572-875) μg/L, p < 0.001) together with oestradiol [(mean ± SD) 78 ± 23 vs. 111 ± 30 pm, p = 0.019], and the oestradiol/testosterone ratio (p = 0.003). By contrast, AMH (42 ± 14 vs. 32 ± 7 pm, p = 0.018), Inhibin B (211 (146-226) vs. 176 (129-204) ng/L, p = 0.059) and LH (3.8 ± 1.5 vs. 3.2 ± 1.2 U/L, p = 0.096) decreased. During pegvisomant treatment IGF-I (204 (160-290) vs. 106 (97-157) μg/L, p = 0.001) and oestradiol (86 ± 28 vs. 79 ± 25 pm, p = 0.060) decreased. No significant changes or trends in the other reproductive hormones occurred during the two treatment regimens. GH/IGF-I activity was positively associated with serum oestradiol, suggesting that GH/IGF-I stimulates aromatase activity in vivo. As a novel observation, we found that high GH activity was associated with reduced levels of the Sertoli cell marker AMH. Further studies are needed to evaluate possible effects of GH on Sertoli cell function and/or spermatogenesis. PMID:23785020

  5. Growth hormone STAT5-mediated signaling and its modulation in mice liver during the growth period.

    PubMed

    Martinez, Carolina S; Piazza, Verónica G; Ratner, Laura D; Matos, Marina N; González, Lorena; Rulli, Susana B; Miquet, Johanna G; Sotelo, Ana I

    2013-01-01

    Postnatal growth exhibits two instances of rapid growth in mice: the first is perinatal and independent of growth hormone (GH), the second is peripuberal and GH-dependent. Signal transducer and activator of transcription 5b (STAT5b) is the main GH-signaling mediator and it is related to IGF1 synthesis and somatic growth. The aim of this work was to assess differential STAT5 sensitivity to GH during the growth period in mouse liver of both sexes. Three representative ages were selected: 1-week-old animals, in the GH-independent phase of growth; 2.5-week-old mice, at the onset of the GH-dependent phase of growth; and 9-week-old young adults. GH-signaling mediators were assessed by immunoblotting, quantitative RT-PCR and immunohistochemistry. GH-induced STAT5 phosphorylation is low at one-week and maximal at 2.5-weeks of age when compared to young adults, accompanied by higher protein content at the onset of growth. Suppressor CIS and phosphatase PTP1B exhibit high levels in one-week animals, which gradually decline, while SOCS2 and SOCS3 display higher levels at adulthood. Nuclear phosphorylated STAT5 is low in one-week animals while in 2.5-week animals it is similar to 9-week control; expression of SOCS3, an early response GH-target gene, mimics this pattern. STAT5 coactivators glucocorticoid receptor (GR) and hepatic nuclear factor 1 (HNF1) abundance is higher in adulthood. Therefore, GH-induced STAT5 signaling presents age-dependent activity in liver, with its maximum coinciding with the onset of GH-dependent phase of growth, accompanied by an age-dependent variation of modulating factors. This work contributes to elucidate the molecular mechanisms implicated in GH responsiveness during growth.

  6. Growth in Boys with 45,X/46,XY Mosaicism: Effect of Growth Hormone Treatment on Statural Growth.

    PubMed

    Bertelloni, Silvano; Baroncelli, Giampiero I; Massart, Francesco; Toschi, Benedetta

    2015-01-01

    45,X/46,XY mosaicism is a rare sex chromosome disorder of sex development. Short stature is a main feature of boys with this condition. Different causes likely contribute to growth impairment. Growth hormone (GH) has been administered to treat short stature in boys with 45,X/46,XY mosaicism, but conflicting data are available. Here, spontaneous growth patterns as well as short- and long-term follow-up studies during GH therapy in these patients are reviewed. Short- and mid-term data showed an improvement of the growth pattern in GH-treated boys, mainly when hormonal therapy was started early, while long-term follow-up demonstrated similar adult heights in GH-treated and untreated patients. Individual biological factors (e.g. different chromosome constitution, different mosaicism among various tissues, impaired pubertal growth spurt), non-homogeneous GH doses and different ages at start of therapy may contribute to the variable results. Thus, early GH therapy at pharmacological doses may improve the growth pattern of short boys with 45,X/46,XY mosaicism, but data on adult height are disappointing. Evaluation of larger patient samples treated by homogeneous doses and long-term follow-up studies assessing adult height and safety are needed to reach definitive conclusions on GH therapy in boys with 45,X/46,XY mosaicism.

  7. Growth in Boys with 45,X/46,XY Mosaicism: Effect of Growth Hormone Treatment on Statural Growth.

    PubMed

    Bertelloni, Silvano; Baroncelli, Giampiero I; Massart, Francesco; Toschi, Benedetta

    2015-01-01

    45,X/46,XY mosaicism is a rare sex chromosome disorder of sex development. Short stature is a main feature of boys with this condition. Different causes likely contribute to growth impairment. Growth hormone (GH) has been administered to treat short stature in boys with 45,X/46,XY mosaicism, but conflicting data are available. Here, spontaneous growth patterns as well as short- and long-term follow-up studies during GH therapy in these patients are reviewed. Short- and mid-term data showed an improvement of the growth pattern in GH-treated boys, mainly when hormonal therapy was started early, while long-term follow-up demonstrated similar adult heights in GH-treated and untreated patients. Individual biological factors (e.g. different chromosome constitution, different mosaicism among various tissues, impaired pubertal growth spurt), non-homogeneous GH doses and different ages at start of therapy may contribute to the variable results. Thus, early GH therapy at pharmacological doses may improve the growth pattern of short boys with 45,X/46,XY mosaicism, but data on adult height are disappointing. Evaluation of larger patient samples treated by homogeneous doses and long-term follow-up studies assessing adult height and safety are needed to reach definitive conclusions on GH therapy in boys with 45,X/46,XY mosaicism. PMID:26529521

  8. Parathyroid hormone secretory pattern, circulating activity, and effect on bone turnover in adult growth hormone deficiency.

    PubMed

    Ahmad, A M; Hopkins, M T; Fraser, W D; Ooi, C G; Durham, B H; Vora, J P

    2003-02-01

    Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Reports have associated parathyroid hormone (PTH) circadian rhythm abnormalities with osteoporosis. Furthermore, there is evidence of relative PTH insensitivity in AGHD patients. Factors regulating PTH circadian rhythm are not fully understood. There is evidence that serum phosphate is a likely determinant of PTH rhythm. The aim of this study was to investigate PTH circadian rhythm and its circulating activity and association with bone turnover in untreated AGHD patients compared to healthy individuals. We sampled peripheral venous blood at 30-min and urine at 3-h intervals during the day over a 24-h period from 1400 h in 14 untreated AGHD patients (7 M, 7 W; mean age, 49.5 +/- 10.7 years) and 14 age (48.6 +/- 11.4 years; P = NS) and gender-matched controls. Cosinor analysis was performed to analyze rhythm parameters. Cross-correlational analysis was used to determine the relationship between variables. Serum PTH (1-84), phosphate, total calcium, urea, creatinine, albumin, type I collagen C-telopeptides (CT(x)), a bone resorption marker, and procollagen type I amino-terminal propeptide (PINP), a bone formation marker, were measured on all samples. Nephrogenous cyclic adenosine monophosphate (NcAMP), which reflects the renal activity of PTH, was calculated from plasma and urinary cAMP. Urinary calcium and phosphate were measured on all urine samples. Significant circadian rhythms were observed for serum PTH, phosphate, CT(x), and PINP in AGHD and healthy subjects (P < 0.001). No significant rhythm was observed for serum-adjusted calcium. PTH MESOR (rhythm-adjusted mean) was significantly higher (P < 0.05), whereas the MESOR values for phosphate, CT(x) (P < 0.05), and PINP (P < 0.001) were lower in AGHD patients than in controls. AGHD patients had significantly lower 24-h NcAMP (P < 0.001) and higher urinary calcium excretion (P < 0.05). Maximum cross-correlation between PTH and phosphate (r = 0

  9. Growth and development in a child with resistance to thyroid hormone and ectopic thyroid gland.

    PubMed

    Heather, Natasha; Hall, Kate; Neas, Katherine; Potter, Howard; Wiltshire, Esko

    2012-03-01

    Resistance to thyroid hormone is an uncommon problem, which has rarely been associated with thyroid dysgenesis. We report a case with both thyroid gland ectopy and resistance to thyroid hormone and, thus, a reduced capacity to produce and respond to thyroid hormone. The patient presented at 2 years of age with developmental delay, dysmorphic features, and elevation in both thyroxine and thyrotropin. We document her response to therapy with thyroxine, with particular regard to her growth and development. Persistent elevation of thyrotropin is commonly recognized during treatment of congenital hypothyroidism. Resistance to thyroid hormone may be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated.

  10. A Rare Corticotroph-Secreting Tumor with Coexisting Prolactin and Growth Hormone Staining Cells

    PubMed Central

    Kannan, Subramanian; Staugaitis, Susan M.; Weil, Robert J.; Hatipoglu, Betul

    2012-01-01

    Pituitary adenomas can express and secrete different hormones. Expression of pituitary hormones in nonneoplastic pituitary cells is regulated by different transcription factors. Some pituitary adenomas show plurihormonal expression. The most commonly reported plurihormonal adenomas are composed of somatotrophs, lactotrophs, thyrotrophs and gonadotrophs. Pituitary adenomas composed of both corticotroph and somatolactotroph secreting cells are not common because transcription factors regulating the expression of these hormones are different. We report a rare case of pituitary adenoma with concomitant corticotroph, prolactin, and growth hormone staining cells, review literature on similar cases, and discuss possible biological mechanisms underlying these plurihormonal tumors. PMID:23320206

  11. Exercise‐Induced growth hormone during acute sleep deprivation

    PubMed Central

    Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

    2014-01-01

    Abstract The effect of acute (24‐h) sleep deprivation on exercise‐induced growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24‐h sessions including a brief, high‐intensity exercise bout following either a night of sleep (SLEEP) or (24‐h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30‐sec Wingate sprints on a cycle ergometer. Self‐reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise‐induced peak GH concentration (TTP), or free IGF‐1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P <0.01), exercise‐induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P <0.01) and ΔGH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise‐induced GH response was significantly augmented in sleep‐deprived individuals. PMID:25281616

  12. Effects of growth hormone (GH) transgene and nutrition on growth and bone development in common carp.

    PubMed

    Zhu, Tingbing; Zhang, Tanglin; Wang, Yaping; Chen, Yushun; Hu, Wei; Zhu, Zuoyan

    2013-10-01

    Limited information is available on effects of growth hormone transgene and nutrition on growth and development of aquatic animals. Here, we present a study to test these effects with growth-enhanced transgenic common carp under two nutritional conditions or feeding rations (i.e., 5% and 10% of fish body weight per day). Compared with the nontransgenic fish, the growth rates of the transgenic fish increased significantly in both feeding rations. The shape of the pharyngeal bone was similar among treatments, but the transgenic fish had relatively smaller and lighter pharyngeal bone compared with the nontransgenic fish. Calcium content of the pharyngeal bone of the transgenic fish was significantly lower than that of the nontransgenic fish. Feeding ration also affected growth rate but less of an effect on bone development. By manipulating intrinsic growth and controlling for both environment (e.g., feeding ration) and genetic background or genotype (e.g., transgenic or not), this study provides empirical evidence that the genotype has a stronger effect than the environment on pharyngeal bone development. The pharyngeal bone strength could be reduced by decreased calcium content and calcification in the transgenic carp.

  13. Sex Hormone-Binding Globulin (SHBG) Expression in Ovarian Carcinomas and Its Clinicopathological Associations

    PubMed Central

    Huang, Ruixia; Ma, Yuanyuan; Holm, Ruth; Trope, Claes G.; Nesland, Jahn M.; Suo, Zhenhe

    2013-01-01

    Sex hormone-binding globulin (SHBG) is known as a carrier protein. It is classically thought to be mainly synthesized in the liver and then secreted into the circulating system, where it binds to sex steroids with a high affinity and modulates the bio-availability of the hormones. Other organs known to produce SHBG include brain, uterus, testis, prostate, breast and ovary, and the local expressed SHBG may play an important role in tumor development. However, SHBG expression status and its clinicopathological significance in ovarian cancer cells are not reported yet. In our present study, we examined and found the variable SHBG expression in four ovarian cancer cell lines (OV-90, OVCAR-3, SKOV-3 and ES-2) by immunocytochemistry and Western blotting. We then extended our study to 248 ovarian carcinoma samples, which were collected at The Norwegian Radium Hospital, Oslo University Hospital with complete clinical information, and discovered that SHBG was variably expressed in these ovarian carcinomas. Higher level of SHBG expression was significantly associated with more aggressive histological subtype (p = 0.022), higher FIGO stage (p = 0.018) and higher histological grade (grade of differentiation, p = 0.020), although association between SHBG expression and OS/PFS was not observed. Our results demonstrate that ovarian cancer cells produce SHBG and higher SHBG expression in ovarian carcinoma is associated with unfavorable clinicopathological features. PMID:24386165

  14. Effects of microgravity on growth hormone concentration and distribution in plants

    NASA Technical Reports Server (NTRS)

    Schulze, Aga; Jensen, Philip; Desrosiers, Mark; Bandurski, Robert S.

    1989-01-01

    On earth, gravity affects the distribution of the plant growth hormone, indole-3-acetic acid (IAA), in a manner such that the plant grows into a normal vertical orientation (shoots up, roots down). How the plant controls the amount and distribution of IAA is only partially understood and is currently under investigation in this laboratory. The question to be answered in the flight experiment concerns the effect of gravity on the concentration, turn over, and distribution of the growth hormone. The answer to this question will aid in understanding the mechanism by which plants control the amount and distribution of growth hormone. Such knowledge of a plant's hormonal metabolism may aid in the growth of plants in space and will lead to agronomic advances.

  15. Restriction fragment length polymorphisms in dairy and beef cattle at the growth hormone and prolactin loci.

    PubMed

    Hallerman, E M; Nave, A; Kashi, Y; Holzer, Z; Soller, M; Beckmann, J S

    1987-01-01

    Two bovine populations, a Holstein-Friesian dairy stock and a synthetic (Baladi X Hereford X Simmental X Charolais) beef stock, were screened for restriction fragment length polymorphisms (RFLPs) at the growth hormone and prolactin genes. Most RFLPs at the growth hormone gene are apparently the consequence of an insertion/deletion event which was localized to a region downstream of the structural gene. The restriction map for the genomic region including the growth hormone gene was extended. Two HindIII RFLPs at the growth hormone locus, as well as several RFLPs at the prolactin gene, seemed to be the consequence of a series of point mutations. The results are discussed in terms of the possibility that minor genomic variability underlies quantitative genetic variation.

  16. A 66-bp deletion in growth hormone releasing hormone gene 5'-flanking region with largemouth bass recessive embryonic lethal.

    PubMed

    Ma, D M; Han, L Q; Bai, J J; Li, S J; Fan, J J; Yu, L Y; Quan, Y C

    2014-06-01

    Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66-bp deletion (c.-923_-858del) was detected in the 5'-flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/- were 2.5:1 and 2.8:1 respectively. Only one -/- fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/-) as parents. The genotype ratio of +/+:+/-:-/- in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66-bp deletion was a recessive lethal site and that homozygous individuals (-/-) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real-time PCR. The effects of genotype (+/-) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66-bp deletion site in GHRH 5'-flanking sequence significantly affects the livability in largemouth bass embryonic development. PMID:24697798

  17. A 66-bp deletion in growth hormone releasing hormone gene 5'-flanking region with largemouth bass recessive embryonic lethal.

    PubMed

    Ma, D M; Han, L Q; Bai, J J; Li, S J; Fan, J J; Yu, L Y; Quan, Y C

    2014-06-01

    Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66-bp deletion (c.-923_-858del) was detected in the 5'-flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/- were 2.5:1 and 2.8:1 respectively. Only one -/- fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/-) as parents. The genotype ratio of +/+:+/-:-/- in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66-bp deletion was a recessive lethal site and that homozygous individuals (-/-) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real-time PCR. The effects of genotype (+/-) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66-bp deletion site in GHRH 5'-flanking sequence significantly affects the livability in largemouth bass embryonic development.

  18. Crustacean hyperglycemic hormone (CHH) neuropeptidesfamily: Functions, titer, and binding to target tissues.

    PubMed

    Chung, J Sook; Zmora, N; Katayama, H; Tsutsui, N

    2010-05-01

    The removal of the eyestalk (s) induces molting and reproduction promoted the presence of regulatory substances in the eyestalk (ES), particularly medulla terminalis X-organ and the sinus gland (MTXO-SG). The PCR-based cloning strategies have allowed for isolating a great number of cDNAs sequences of crustacean hyperglycemic hormone (CHH) neuropeptides family from the eyestalk and non-eyestalk tissues, e.g., pericardial organs and fore- and hindguts. However, the translated corresponding neuropeptides in these tissues, their circulating concentrations, the mode of actions, and specific physiological functions have not been well described. The profiles of CHH neuropeptides present in the MTXO-SG may differ among decapod crustacean species, but they can be largely divided into two sub-groups on the basis of structural homology: (1) CHH and (2) molt-inhibiting hormone (MIH)/mandibular organ-inhibiting hormone (MOIH)/vitellogenesis/gonad-inhibiting hormone (V/GIH). CHH typically elevating the level of circulating glucose from animals under stressful conditions (hyper- and hypothermia, hypoxia, and low salinity) has multiple target tissues and functions such as ecdysteroidogenesis, osmoregulation, and vitellogenesis. Recently, MIH, known for exclusively suppressing ecdysteroidogenesis in Y-organs, is also reported to have an additional role in vitellogenesis of adult female crustacean species, suggesting that some CHH neuropeptides may acquire an extra regulatory role in reproduction at adult stage. This paper reviews the regulatory roles of CHH and MIH at the levels of specific functions, temporal and spatial expression, titers, their binding sites on the target tissues, and second messengers from two crab species: the blue crab, Callinectes sapidus, and the European green crab, Carcinus maenas. It further discusses the diverse regulatory roles of these neuropeptides and the functional plasticity of these neuropeptides in regard to life stage and species

  19. Growth hormone and anabolic steroids: athletes are the tip of the iceberg.

    PubMed

    Perls, Thomas T

    2009-09-01

    Professional Athletes' misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and "anti-aging". Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors. PMID:20355224

  20. Growth hormone and anabolic steroids: athletes are the tip of the iceberg.

    PubMed

    Perls, Thomas T

    2009-09-01

    Professional Athletes' misuse of anabolic steroids, growth hormone and other drugs are the tip of a very large, mostly ignored iceberg, made up of people who receive these drugs for such non-medical uses as body-building, school sports and "anti-aging". Although these drugs are often used in combination, this article focuses on growth hormone. Fuelling the demand for these drugs are drug manufacturers, pharmacies, websites, clinics and their doctors.

  1. Induction of chronic growth hormone deficiency by anti-GH serum

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.; Smith, A. T.; Ellis, S.; Evans, E. S.

    1974-01-01

    The observations reported indicate that the growth rate of neonatal rats can be specifically inhibited for at least 78 days following the administration of antisera against growth hormone (GH) for only four days after birth. The inhibition can be correlated with a marked deficit of tibial growth promoting activity in the pituitary but not with the plasma concentrations of immuno-reactive GH.

  2. Genetic effects on serum testosterone and sex hormone-binding globulin in men: a Korean twin and family study

    PubMed Central

    Sung, Joohon; Song, Yun-Mi

    2016-01-01

    We conducted a community-based cross-sectional study to evaluate the role of genetics in determining the individual difference in total testosterone and sex hormone-binding globulin levels. Study participants comprised 730 Korean men consisting of 142 pairs of monozygotic twins, 191 pairs of siblings, and 259 father-offspring pairs from 270 families who participated in the Healthy Twin study. Serum concentration of total testosterone and sex hormone-binding globulin were measured by chemiluminescence immunoassay, and free testosterone and bioavailable testosterone were calculated using Vermeulen's method. Quantitative genetic analysis based on a variance decomposition model showed that the heritability of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin were 0.56, 0.45, 0.44, and 0.69, respectively after accounting for age and body mass index. Proportions of variance explained by age and body mass index varied across different traits, from 8% for total testosterone to 31% for sex hormone-binding globulin. Bivariate analysis showed a high degree of additive genetic correlation (ρG = 0.67) and a moderate degree of individual-specific environmental correlation (ρE = 0.42) between total testosterone and sex hormone-binding globulin. The findings confirmed the important role of genetics in determining the individually different levels of testosterone and sex hormone-binding globulin during adulthood in Korean men as found in non-Asian populations, which may suggest that common biologic control for determining testosterone level directly or indirectly through binding protein are largely shared among different populations. PMID:26486061

  3. Leptin activates chicken growth hormone promoter without chicken STAT3 in vitro.

    PubMed

    Murase, Daisuke; Namekawa, Shoko; Ohkubo, Takeshi

    2016-01-01

    Leptin is an adipocyte-derived hormone that not only regulates food intake and energy homeostasis but also induces growth hormone (GH) mRNA expression and release, thereby controlling growth and metabolism in mammals. The molecular mechanism of leptin-induced regulation of GH gene transcription is unclear. The current study investigated the effects of leptin on the chicken GH (cGH) promoter and the molecular mechanism underlying leptin-induced cGH gene expression in vitro. Leptin activated the cGH promoter in the presence of chPit-1α in CHO cells stably expressing the chicken leptin receptor. Promoter activation did not require STAT-binding elements in the cGH promoter or STAT3 activity. However, JAK2 activation was required for leptin-dependent activity. JAK2-dependent pathways include p42/44 MAPK and PI3K, and inhibition of these pathways partially blocked leptin-induced cGH gene transcription. Although CK2 directly activates JAK2, a CK2 inhibitor blocked leptin-dependent activation of the cGH gene without affecting JAK2 phosphorylation. The CK2 inhibitor suppressed Erk1/2 and Akt phosphorylation. Additional data implicate Src family kinases in leptin-dependent cGH gene activation. These results suggest that leptin activates the cGH gene in the presence of chPit-1α via several leptin-activated kinases. Although further study is required, we suggest that the leptin-induced JAK2/p42/44 MAPK and JAK2/PI3K cascades are activated by Src-meditated CK2, leading to CBP phosphorylation and interaction with chPit-1α, resulting in transactivation of the cGH promoter.

  4. Growth hormone activates phospholipase C in proximal tubular basolateral membranes from canine kidney

    SciTech Connect

    Rogers, S.A.; Hammerman, M.R. )

    1989-08-01

    To delineate pathways for signal transduction by growth hormone (GH) in proximal tubule, the authors incubated basolateral membranes isolated from canine kidney with human growth hormone (hGH) or human prolactin (hPrl) and measured levels of inositol trisphosphate (InsP{sub 3}) in suspensions and of diacylglycerol extractable from the membranes. Incubation with hGH, but not hPrl, increased levels of InsP{sub 3} and diacylglycerol in a concentration-dependent manner. Half-maximal effects occurred between 0.1 and 1 nM hGH. Increased levels of InsP{sub 3} were measured after as little as 5 sec of incubation with 1 nM hGH, and increase was maximal after 15 sec. Increases were no longer detectable after 60 sec because of dephosphorylation of InsP{sub 3} in membrane suspensions. hGH did not affect rates of dephosphorylation. hGH-stimulated increases in InsP{sub 3} were detectable in membranes suspended in 0, 0.1, and 0.2 {mu}M calcium but not in 0.3 or 1.0 {mu}M calcium. {sup 125}I-labeled hGH-receptor complexes with M{sub r} values of 66,000 and 140,000 were identified in isolated basolateral membranes. The findings establish that GH activates phospholipase C in isolated canine renal proximal tubular basolateral membranes, potentially after binding to a specific receptor. This process could mediate signal transmission by GH across the plasma membrane of the proximal tubular cell and elsewhere.

  5. Why Treat girls with Turner Syndrome with Growth Hormone? Growth and Beyond.

    PubMed

    Ranke, Michael B

    2015-06-01

    Turner Syndrome (TS) is a rare disorder, characterized by numerous signs and symptoms, which are also highly variable in their expression in individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. The most consistent features, which negatively affect the quality of life in these individuals, are short stature and impaired gonadal function. After recombinant human growth hormone (rhGH) became available and was shown to improve height, it was then approved and has been used widely. Yet it remains a challenge to decide on the optimal treatment modality for individuals with TS and to evaluate the benefits and risks also in terms of karyotype of GH on growth and on other organ systems. This article reviews some of the major aspects related to these issues.

  6. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan. PMID:25300732

  7. Growth hormone and insulin-like growth factor I in a Sydney Olympic gold medallist.

    PubMed

    Armanini, D; Faggian, D; Scaroni, C; Plebani, M

    2002-04-01

    An Italian athlete who won a gold medal at the Sydney Olympic Games was studied. She was accused of doping after the finding of high levels of plasma growth hormone (GH) before the Games. She was studied firstly under stressed and then under unstressed conditions. In the first study, GH was measured every 20 minutes for one hour; it was above the normal range in all blood samples, whereas insulin-like growth factor I (IGF-I) was normal. In the second study, GH progressively returned to accepted normal levels; IGF-I was again normal. It was concluded that the normal range for GH in athletes must be reconsidered for doping purposes, because athletes are subject to stress and thus to wide variations in GH levels. PMID:11916901

  8. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.

  9. Why Treat girls with Turner Syndrome with Growth Hormone? Growth and Beyond.

    PubMed

    Ranke, Michael B

    2015-06-01

    Turner Syndrome (TS) is a rare disorder, characterized by numerous signs and symptoms, which are also highly variable in their expression in individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. The most consistent features, which negatively affect the quality of life in these individuals, are short stature and impaired gonadal function. After recombinant human growth hormone (rhGH) became available and was shown to improve height, it was then approved and has been used widely. Yet it remains a challenge to decide on the optimal treatment modality for individuals with TS and to evaluate the benefits and risks also in terms of karyotype of GH on growth and on other organ systems. This article reviews some of the major aspects related to these issues. PMID:26182480

  10. Microarchitecture, but not bone mechanical properties, is rescued with growth hormone treatment in a mouse model of growth hormone deficiency.

    PubMed

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27-52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD. PMID:22505889

  11. Transgenic medaka that overexpress growth hormone have a skin color that does not indicate the activation or inhibition of somatolactin-α signal.

    PubMed

    Komine, Ritsuko; Nishimaki, Toshiyuki; Kimura, Tetsuaki; Oota, Hiroki; Naruse, Kiyoshi; Homma, Noriko; Fukamachi, Shoji

    2016-06-10

    Teleosts have two paralogous growth-hormone receptors (GHRs). In vitro studies demonstrated that both receptors bind to and transmit the signal of the growth hormone (GH). However, one of the GHRs (GHR1) was shown to bind more strongly to somatolactin-α (SLα), a fish-specific peptide hormone that is closely related to GH, and is, therefore, termed somatolactin receptor (SLR). In this study, we questioned whether the dual binding of GHR1/SLR causes a crosstalk (reciprocal activation or inhibition) between GH and SLα signals in vivo. For this purpose, we newly established a transgenic medaka that overexpresses GH (Actb-GH:GFP) and assessed its phenotype. The body weight of these transgenic medaka is about twice that of wild-type fish, showing that functional GH was successfully overexpressed in Actb-GH:GFP fish. The transgenic medaka, especially female fish, showed severe infertility, which was a common side effect in GH transgenesis. The skin color, which reflects the effects of SLα most conspicuously in medaka, was similar to that of neither the SLα-overexpressing nor the SLα-deficient medaka, indicating that GH overexpression does not enhance or suppress the SLα signal. We also verified that a transgenic medaka that overexpressed SLα grew and reproduced normally. Therefore, regardless of the in vitro binding relationships, the GH and SLα signals seem not to crosstalk significantly in vivo even when these hormones are overexpressed.

  12. Heterogeneity of epidermal growth factor binding kinetics on individual cells.

    PubMed Central

    Chung, J C; Sciaky, N; Gross, D J

    1997-01-01

    Binding of fluorescein-conjugated epidermal growth factor (EGF) to individual A431 cells at 4 degrees C is measured by a quantitative fluorescence imaging technique. After background fluorescence and cell autofluorescence photobleaching corrections, the kinetic data are fit to simple models of one monovalent site and two independent monovalent sites, both of which include a first-order dye photobleaching process. Model simulations and the results from data analysis indicate that the one-monovalent-site model does not describe EGF binding kinetics at the single-cell level, whereas the two-site model is consistent with, but not proved by, the single-cell binding data. In addition, the kinetics of binding of fluorescein-EGF to different cells from the same coverslip often differ significantly from each other, indicating cell-to-cell variations in the binding properties of the EGF receptor. PMID:9251825

  13. Corticosteroid-binding globulin, cortisol, free cortisol, and sex hormone-binding globulin responses following oral glucose challenge in spinal cord-injured and able-bodied men.

    PubMed

    Lewis, J G; Jones, L M; Legge, M; Elder, P A

    2010-11-01

    Circulating cortisol, corticosteroid-binding globulin, and sex hormone-binding globulin were measured retrospectively in plasma samples following the oral glucose tolerance test in 20 spinal cord-injured men and 20 able-bodied controls. Plasma-free cortisol responses attenuated more rapidly in the able-bodied men, compared to spinal cord-injured subjects, due to significant rise in circulating corticosteroid-binding globulin whereas changes in total plasma cortisol were similar in both groups. The changes in plasma-free cortisol in both groups paralleled changes in insulin and glucose and show that spinal cord-injured men had heightened exposure to free cortisol during this dynamic test. This raises the possibility that the mechanism of abdominal obesity and the propensity towards insulin resistance in spinal cord-injured men could be subtly mediated by perturbations in free cortisol. There were no significant changes in plasma sex hormone-binding globulin in either group.

  14. Periplasmic production via the pET expression system of soluble, bioactive human growth hormone.

    PubMed

    Sockolosky, Jonathan T; Szoka, Francis C

    2013-02-01

    A pET based expression system for the production of recombinant human growth hormone (hGH) directed to the Escherichia coli periplasmic space was developed. The pET22b plasmid was used as a template for creating vectors that encode hGH fused to either a pelB or ompA secretion signal under control of the strong bacteriophage T7 promoter. The pelB- and ompA-hGH constructs expressed in BL21 (λDE3)-RIPL E. coli are secreted into the periplasm which facilitates isolation of soluble hGH by selective disruption of the outer membrane. A carboxy-terminal poly-histidine tag enabled purification by Ni(2+) affinity chromatography with an average yield of 1.4 mg/L culture of purified hGH, independent of secretion signal. Purified pelB- and ompA-hGH are monomeric based on size exclusion chromatography with an intact mass corresponding to mature hGH indicating proper cleavage of the signal peptide and folding in the periplasm. Both pelB- and ompA-hGH bind the hGH receptor with high affinity and potently stimulate Nb2 cell growth. These results demonstrate that the pET expression system is suitable for the rapid and simple isolation of bioactive, soluble hGH from E. coli.

  15. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats.

    PubMed

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway. PMID:27445863

  16. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats

    PubMed Central

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway. PMID:27445863

  17. Modulation of Mammary Gland Development and Milk Production by Growth Hormone Expression in GH Transgenic Goats.

    PubMed

    Bao, Zekun; Lin, Jian; Ye, Lulu; Zhang, Qiang; Chen, Jianquan; Yang, Qian; Yu, Qinghua

    2016-01-01

    Mammary gland development during puberty and reconstruction during pregnancy and lactation is under the control of circulating endocrine hormones, such as growth hormone, which are released from the pituitary. In this study, we explored the influence of overexpression of growth hormone in the mammary gland on breast development and milk production in goats. Using transcriptome sequencing, we found that the number of highly expressed genes was greater in GH transgenic goats than non-transgenic goats. Furthermore, KEGG pathway analysis showed that the majority of the genes belonged to the MAPK signaling pathway and the ECM-receptor interaction pathway. The expression of genes related to breast development was further confirmed using qRT-PCR. Interestingly, both milk production and milk quality were increased. The results of these experiments imply that overexpression of growth hormone in the breast may stimulate breast development and enhances milk production by modulating alveolar cell proliferation or branching through the MAPK signaling pathway.

  18. Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study.

    PubMed Central

    Böger, R H; Skamira, C; Bode-Böger, S M; Brabant, G; von zur Muhlen, A; Frolich, J C

    1996-01-01

    We studied the effects of recombinant growth hormone on systemic nitric oxide (NO) formation and hemodynamics in a double-blind, placebo-controlled trial in adult patients with acquired growth hormone deficiency. 30 patients were randomly allocated to either recombinant human growth hormone (r-hGH; 2.0 IU/d) or placebo for 12 mo. In the subsequent 12 mo, the study was continued with both groups of patients receiving r-hGH. In months 1, 3, 6, 9, and 12 of each year, urine and plasma samples were collected for the determination of urinary nitrate and cyclic GMP as indices of systemic NO production, and of plasma IGF-1 levels. Cardiac output was measured in months 1, 12, and 24 by echocardiography. r-hGH induced a fourfold increase in plasma IGF-1 concentrations within the first month of treatment. Urinary nitrate and cyclic GMP excretion rates were low at baseline in growth hormone-deficient patients (nitrate, 96.8+/-7.4 micromol/mmol creatinine; cyclic GMP, 63.6+/-7.1 nmol/mmol creatinine) as compared with healthy controls (nitrate, 167.3+/-7.5 micromol/mmol creatinine; cyclic GMP, 155.2+/-6.9 nmol/mmol creatinine). These indices of NO production were significantly increased by r-hGH, within the first 12 mo in the GH group, and within the second 12 mo in the placebo group. While systolic and diastolic blood pressure were not significantly altered by r-hGH, cardiac output significantly increased by 30-40%, and total peripheral resistance decreased by approximately 30% in both groups when they were assigned to r-hGH treatment. In the second study year, when both groups were given r-hGH, there were no significant differences in plasma IGF-1, urinary nitrate, or cyclic GMP excretion, or hemodynamic parameters between both groups. In conclusion, systemic NO formation is decreased in untreated growth hormone-deficient patients. Treatment with recombinant human growth hormone normalizes urinary nitrate and cyclic GMP excretion, possibly via IGF-1 stimulation of endothelial

  19. Growth and endocrine effect of growth hormone transgene dosage in diploid and triploid coho salmon.

    PubMed

    Devlin, Robert H; Sakhrani, Dionne; Biagi, Carlo A; Smith, Jack L; Fujimoto, Takafumi; Beckman, Brian

    2014-01-15

    Growth-hormone transgene dosage, polyploidy, and parental effects on growth and endocrine responses have been assessed in coho salmon. Diploid fry with one or two transgene doses grew equally, whereas later-stage juvenile homozygotes grew faster than hemizygotes. In contrast, homozygotes and hemizygotes grew equally after smoltification, both in sea water and fresh water. Triploid transgenic salmon showed impaired growth which could not be fully overcome with additional transgene copies. Levels of muscle GH mRNA were elevated in two vs. one transgene dose diploids, but in triploids, a dosage effect was observed in muscle but not for animals carrying three transgene doses. IGF-I mRNA levels were elevated in transgenic vs. non-transgenic animals, but a dosage effect was not observed. Diploids and triploids with two transgenes had higher plasma GH levels than one-dose animals, but three-dose triploids showed no further elevation. Circulating IGF-I levels also showed a dosage effect in diploids, but not among any transgene doses in triploids. The present study reveals complex interactions among transgene dosage, maternal effects, developmental stage, and ploidy on growth and endocrine parameters in GH transgenic coho salmon. Specifically, GH transgenes do not always express nor have effects on growth that are directly correlated with the number of transgenes. Further, the reduced growth rate seen in triploid transgenic animals could not be fully overcome by increasing transgene dosage. The findings have relevance for understanding growth physiology, transgene function, and for environmental risk assessments that require understanding phenotypes of hemizygous vs. homozygous transgenic animals in populations.

  20. Overexpression of the short form of the growth hormone receptor in 3T3-L1 mouse preadipocytes

    SciTech Connect

    Bick, T.; Frick, G.P.; Leonard, D.

    1994-12-31

    In rodents, the gene for the growth hormone receptor (GHR) gives rise to two mRNA transcripts encoding two proteins: a larger membrane spanning receptor (GHR{sub L}) and a smaller isoform, GHR{sub S} that consists of the extracellular domain and a unique hydrophillic carboxyl terminus. We examined the hypothesis that GHR{sub S} may contribute to cellular binding of GH and play a role in growth hormone (GH) signaling. Rat cDNA encoding GHR{sub S} was ligated into the mammalian expression vector pcDNA-I/neo and stably transfected into mouse 3T3-L1 preadipocytes which have endogenous GH receptors and, when differentiated into adipocytes, have the biochemical machinery to express the various GH effects. Sixteen of 24 neomycin resistant clones secreted at least twice as much GHR{sub s} in the growth medium as cells transfected with the vector alone, and in nine of these, GH binding was increased 2- to 4-fold. The amount of GHR{sub L} in extracts of these cells was unchanged, indicating that increased binding could not be accounted for by effects on formation or degradation of GHR{sub L}. The transfected cDNA for GHR{sub S} directs the synthesis of a 50 kDa protein. We conclude that GHR{sub S} contributes to GH binding and may therefore be a functional receptor. In addition, overexpression of GHR{sub S} in 3T3-L1 cells altered cell function in the absence of GH. 20 refs., 4 figs.

  1. Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

    PubMed

    Childs, G V

    2002-04-01

    The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

  2. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition

    PubMed Central

    Reitz, M. U.; Gifford, M. L.; Schäfer, P.

    2015-01-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth–immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth–immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth–immunity cross-talk. PMID:25821072

  3. Position stand on androgen and human growth hormone use.

    PubMed

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

  4. Position stand on androgen and human growth hormone use.

    PubMed

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

  5. Rooster feathering, androgenic alopecia, and hormone dependent tumor growth: What is in common?

    PubMed Central

    Mayer, Julie Ann; Chuong, Cheng-Ming; Widelitz, Randall

    2015-01-01

    Different epithelial organs form as a result of epithelial - mesenchymal interactions and share a common theme modulated by variations (Chuong edit. In Molecular Basis of Epithelial Appendage Morphogenesis, 1998). One of the major modulators is the sex hormone pathway that acts on the prototype signaling pathway to alter organ phenotypes. Here we focus on how the sex hormone pathway interfaces with epithelia morphogenesis related signaling pathways. We first survey these sex hormone regulated morphogenetic processes in various epithelial organs. Sexual dimorphism of hairs and feathers has implications in sexual selection. Diseases of these pathways result in androgenic alopecia, hirsutism, henny feathering, etc. The growth and development of mammary glands, prostate glands and external genitalia essential for reproductive function are also dependent on sex hormones. Diseases affecting these organs include congenital anomalies and hormone dependent type of breast and prostate cancers. To study the role of sex hormones in new growth in the context of system biology / pathology, an in vivo model in which organ formation starts from stem cells is essential. With recent developments (Yu et al., The morphogenesis of feathers. Nature 420:308–312, 2002), the growth of tail feathers in roosters and hens has become a testable model in which experimental manipulations are possible. We show exemplary data of differences in their growth rate, proliferative cell population and signaling molecule expression. Working hypotheses are proposed on how the sex hormone pathways may interact with growth pathways. It is now possible to test these hypotheses using the chicken model to learn fundamental mechanisms on how sex hormones affect organogenesis, epithelial organ cycling, and growth related tumorigenesis. PMID:15617560

  6. Development of Follicle-Stimulating Hormone Receptor Binding Probes to Image Ovarian Xenografts

    PubMed Central

    Lee, Chung-Wein; Guo, Lili; Matei, Daniela; Stantz, Keith

    2015-01-01

    The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells in vitro and tumors xenograft model in vivo. The in vitro binding curve and the average number of FSHR per cell are obtained for OVCAR-3 cells by a high resolution flow cytometer. For the decapeptide, the measured EC50 was 160 μM and the average number of receptors per cell was 1.7 × 107. The decapeptide molecular imaging probe reached a maximum tumor to muscle ratio five hours after intravenous injection and a dose-dependent plateau after 24–48 hours. These results indicate the potential application of a small molecular weight imaging probe specific to ovarian cancer through binding to FSHR. Based on these results, multimeric constructs are being developed to optimize binding t