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Sample records for aas growth hormone

  1. 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 ...

  2. Growth hormone suppression test

    MedlinePlus

    The growth hormone suppression test determines whether growth hormone production is being suppressed by high blood sugar. ... away. The lab measures the glucose and growth hormone (GH) levels in each sample.

  3. 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 ...

  4. Growth hormone suppression test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  5. 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 ...

  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. 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

  8. Growth hormone stimulation test

    MedlinePlus

    The growth hormone (GH) stimulation test measures the ability of the body to produce GH. ... killing medicine (antiseptic). The first sample is drawn early in the morning. Medicine is given through the ...

  9. [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. PMID:20502852

  10. 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…

  11. The growth hormone receptor.

    PubMed

    Waters, Michael J

    2016-06-01

    Once thought to be present only in liver, muscle and adipose tissue, the GH receptor is now known to be ubiquitously distributed, in accord with the many pleiotropic actions of GH. These include the regulation of metabolism, postnatal growth, cognition, immune, cardiac and renal systems and gut function. GH exerts these actions primarily through alterations in gene expression, initiated by activation of its membrane receptor and the resultant activation of the associated JAK2 (Janus kinase 2) and Src family kinases. Receptor activation involves hormone initiated movements within a receptor homodimer, rather than simple receptor dimerization. We have shown that binding of the hormone realigns the orientation of the two receptors both by relative rotation and by closer apposition just above the cell membrane. This is a consequence of the asymmetric placement of the binding sites on the hormone. Binding results in a conversion of parallel receptor transmembrane domains into a rotated crossover orientation, which produces separation of the lower part of the transmembrane helices. Because the JAK2 is bound to the Box1 motif proximal to the inner membrane, receptor activation results in separation of the two associated JAK2s, and in particular the removal of the inhibitory pseudokinase domain from the kinase domain of the other JAK2 (and vice versa). This brings the two kinase domains into position for trans-activation and initiates tyrosine phosphorylation of the receptor cytoplasmic domain and other substrates such as STAT5, the key transcription factor mediating most genomic actions of GH. There are a limited number of genomic actions initiated by the Src kinase family member which also associates with the upper cytoplasmic domain of the receptor, including important immune regulatory actions to dampen exuberant innate immune activation of cells involved in transplant rejection. These findings offer insights for developing specific receptor antagonists which may be

  12. Growth hormone stimulation test (image)

    MedlinePlus

    ... test is performed by administering the amino acid arginine in a vein to raise hGH levels. The ... to secrete growth hormone in response to the arginine. Lack of hGH can cause growth retardation in ...

  13. 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 ...

  14. Growth hormone signaling pathways.

    PubMed

    Carter-Su, Christin; Schwartz, Jessica; Argetsinger, Lawrence S

    2016-06-01

    Over 20years ago, our laboratory showed that growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway; 4) signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown that SH2B1β is recruited to and phosphorylated by JAK2 in response to GH. SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight. PMID:26421979

  15. 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

  16. Genetics of growth hormone deficiency.

    PubMed

    Mullis, Primus E

    2007-03-01

    When a child is not following the normal, predicted growth curve, an evaluation for underlying illness and central nervous system abnormalities is required and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency. This article focuses on the GH gene, the various gene alterations, and their possible impact on the pituitary gland. Transcription factors regulating pituitary gland development may cause multiple pituitary hormone deficiency but may present initially as GH deficiency. The role of two most important transcription factors, POU1F1 (Pit-1) and PROP 1, is discussed. PMID:17336732

  17. Growth hormone deficiency - children

    MedlinePlus

    ... gender. The child will still have normal body proportions, but may be chubby. The child's face often ... A physical exam, including weight, height, and body proportions, will show signs of slowed growth. The child ...

  18. 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 ...

  19. 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.

  20. 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. PMID:23435439

  1. 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

  2. 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

  3. 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

  4. [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

  5. 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

  6. 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. PMID:26775014

  7. 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.…

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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…

  13. 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.

  14. 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

  15. Neuroendocrine Regulation of Growth Hormone Secretion.

    PubMed

    Steyn, Frederik J; Tolle, Virginie; Chen, Chen; Epelbaum, Jacques

    2016-01-01

    This article reviews the main findings that emerged in the intervening years since the previous volume on hormonal control of growth in the section on the endocrine system of the Handbook of Physiology concerning the intra- and extrahypothalamic neuronal networks connecting growth hormone releasing hormone (GHRH) and somatostatin hypophysiotropic neurons and the integration between regulators of food intake/metabolism and GH release. Among these findings, the discovery of ghrelin still raises many unanswered questions. One important event was the application of deconvolution analysis to the pulsatile patterns of GH secretion in different mammalian species, including Man, according to gender, hormonal environment and ageing. Concerning this last phenomenon, a great body of evidence now supports the role of an attenuation of the GHRH/GH/Insulin-like growth factor-1 (IGF-1) axis in the control of mammalian aging. © 2016 American Physiological Society. Compr Physiol 6:687-735, 2016. PMID:27065166

  16. 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- ...

  17. 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...

  18. Peripheral activities of growth hormone-releasing hormone.

    PubMed

    Granata, R

    2016-07-01

    Growth hormone (GH)-releasing hormone (GHRH) is produced by the hypothalamus and stimulates GH synthesis and release in the anterior pituitary gland. In addition to its endocrine role, GHRH exerts a wide range of extrapituitary effects which include stimulation of cell proliferation, survival and differentiation, and inhibition of apoptosis. Accordingly, expression of GHRH, as well as the receptor GHRH-R and its splice variants, has been demonstrated in different peripheral tissues and cell types. Among the direct peripheral activities, GHRH regulates pancreatic islet and β-cell survival and function and endometrial cell proliferation, promotes cardioprotection and wound healing, influences the immune and reproductive systems, reduces inflammation, indirectly increases lifespan and adiposity and acts on skeletal muscle cells to inhibit cell death and atrophy. Therefore, it is becoming increasingly clear that GHRH exerts important extrapituitary functions, suggesting potential therapeutic use of the peptide and its analogs in a wide range of medical settings. PMID:26891937

  19. 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…

  20. 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...

  1. 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)

  2. Climacteric in untreated isolated growth hormone deficiency

    PubMed Central

    Menezes, Menilson; Salvatori, Roberto; Oliveira, Carla R.P.; Pereira, Rossana M.C.; Souza, Anita H.O.; Nobrega, Luciana M.A.; Cruz, Edla do A.C.; Menezes, Marcos; Alves, Érica O.; Aguiar-Oliveira, Manuel H.

    2008-01-01

    Objective To study the time, intensity of symptoms, hormonal profile, and related morbidity of climacteric in women with untreated isolated growth hormone (GH) deficiency (IGHD). Design Women belonging to a large Brazilian kindred with IGHD due to a homozygous mutation in the GH-releasing hormone receptor gene were studied. None of them had ever received GH replacement therapy. A two-step protocol was performed. In the first case-control experiment, aimed to determine the age at climacteric, we compared eight women with IGHD and 32 normal women between 37 and 55 years of age. In the second cross-sectional experiment, aimed to determine the severity of climacteric symptoms, seven women with IGHD (aged 47-65 y) were compared with 13 controls (aged 44-65 y). The Kupperman Index scores, serum follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol levels were determined, and pelvic and mammary ultrasonography, mammography, and colpocytology were performed. Results The number of women with follicle-stimulating hormone above 20 mIU/mL was higher in women with IGHD than controls. Kupperman’s Index was not different between the two groups. Menarche had been delayed and parity was lower in women with IGHD. Hormonal profile was similar, but prolactin was lower in women with IGHD. Uterine volume was smaller in women with IGHD, and endometrial thickness and ovarian volume were similar in the two groups. No difference in breast images or in colpocytology was observed between the two groups. Conclusions Menarche was delayed and the beginning of climacteric is anticipated in untreated lifetime IGHD, but menopausal symptoms and hormonal profile resemble the normal climacteric. PMID:18223507

  3. 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

  4. Growth hormone, growth factors, and acromegaly

    SciTech Connect

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  5. 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.

  6. Cardiovascular Risk in Growth Hormone Deficiency: Beneficial Effects of Growth Hormone Replacement Therapy.

    PubMed

    Lanes, Roberto

    2016-06-01

    Growth hormone deficiency (GHD) in adulthood is associated with an increased risk of developing adverse cardiovascular events and with reduced life expectancy. Cardiovascular and metabolic abnormalities have so far been evaluated only in a small number of children with GHD and adolescents. In this article we review these abnormalities and their underlying mechanisms and discuss the beneficial effect of growth hormone treatment in subjects with GHD. PMID:27241971

  7. Information for People Treated with Human Growth Hormone (Summary)

    MedlinePlus

    ... Program (NHPP): Information for People Treated with Pituitary Human Growth Hormone (Summary) Page Content On this page: ... disease (CJD) occur in people treated with pituitary human growth hormone (hGH)? How many people treated with ...

  8. 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)

  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. 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.

  11. PEGylation of growth hormone-releasing hormone (GRF) analogues.

    PubMed

    Esposito, P; Barbero, L; Caccia, P; Caliceti, P; D'Antonio, M; Piquet, G; Veronese, F M

    2003-09-26

    Synthetically produced GRF1-29 (Sermorelin) has an amino acid composition identical to the N-terminal 29 amino acids sequence of the natural hypothalamic GHRH1-44 (Figure 1). It maintains bioactivity in vitro and is almost equally effective in eliciting secretion of endogenous growth hormone in vivo. The main drawbacks associated with the pharmaceutical use of hGRF1-29 relate to its short half-life in plasma, about 10-20 min in humans, which is caused mostly by renal ultrafiltration and enzymatic degradation at the N terminus. PEGylation has been considered as one valid approach to obtain more stable forms of the peptide, with a longer in vivo half-life and ultimately with increased pharmacodynamic response along the somatotropic axis (endogenous GH, IGF-1 levels). Different PEGylated GRF conjugates were obtained and their bioactivity was tested in vitro and in vivo by monitoring endogenous growth hormone (GH) serum levels after intravenous (i.v.) injection in rats, and intravenous and subcutaneous (s.c.) injection in pigs. It was found that GRF-PEG conjugates are able to bind and activate the human GRF receptor, although with different potency. The effect of PEG molecular weight, number of PEG chains bound and position of PEGylation site on GRF activity were investigated. Mono-PEGylated isomers with a PEG5000 polymer chain linked to Lys 12 or Lys 21 residues, showed high biological activity in vitro, which is similar to that of hGRF1-29, and a higher pharmacodynamic response as compared to unmodified GRF molecule. PMID:14499707

  12. 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

  13. 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.

  14. Dimerization of Human Growth Hormone by Zinc

    NASA Astrophysics Data System (ADS)

    Cunningham, Brian C.; Mulkerrin, Michael G.; Wells, James A.

    1991-08-01

    Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn2+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.

  15. Netherton syndrome associated with growth hormone deficiency.

    PubMed

    Aydın, Banu Küçükemre; Baş, Firdevs; Tamay, Zeynep; Kılıç, Gürkan; Süleyman, Ayşe; Bundak, Rüveyde; Saka, Nurçin; Özkaya, Esen; Güler, Nermin; Darendeliler, Feyza

    2014-01-01

    Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by ichthyosiform scaling, hair abnormalities, and variable atopic features. Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth retardation is a classic feature of NS, but growth hormone (GH) deficiency with subsequent response to GH therapy is not documented in the literature. It is proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in the pituitary gland leads to the overprocessing of human GH in NS. Herein we report three patients with NS who had growth retardation associated with GH deficiency and responded well to GH therapy. PMID:24015757

  16. 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

  17. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    PubMed

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland. PMID:27052215

  18. 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. PMID:19955758

  19. 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.

  20. A history of growth hormone injection devices.

    PubMed

    Fidotti, E

    2001-05-01

    In the early 1960s, growth hormone (GH) deficiency was treated by intramuscular injection of GH extracted from human pituitary glands. Since then, there have been many advances in treatment encompassing the route of administration, the injection product and the injection device. This review considers the advances in injection device that have already taken place and how they have benefited the patient, particularly in terms of reduced pain and improved convenience. In the future, needle-free injection techniques and depot formulations of GH are likely to offer alternatives to daily subcutaneous injections. PMID:11393569

  1. 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.

  2. 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

  3. 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)…

  4. Growth hormone deficiency and cerebral palsy

    PubMed Central

    Devesa, Jesús; Casteleiro, Nerea; Rodicio, Cristina; López, Natalia; Reimunde, Pedro

    2010-01-01

    Cerebral palsy (CP) is a catastrophic acquired disease, occurring during development of the fetal or infant brain. It mainly affects the motor control centres of the developing brain, but can also affect cognitive functions, and is usually accompanied by a cohort of symptoms including lack of communication, epilepsy, and alterations in behavior. Most children with cerebral palsy exhibit a short stature, progressively declining from birth to puberty. We tested here whether this lack of normal growth might be due to an impaired or deficient growth hormone (GH) secretion. Our study sample comprised 46 CP children, of which 28 were male and 18 were female, aged between 3 and 11 years. Data obtained show that 70% of these children lack normal GH secretion. We conclude that GH replacement therapy should be implemented early for CP children, not only to allow them to achieve a normal height, but also because of the known neurotrophic effects of the hormone, perhaps allowing for the correction of some of the common disabilities experienced by CP children. PMID:20856687

  5. 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. PMID:24251151

  6. Growth hormone-insulinlike growth factor I and immune function.

    PubMed

    Gelato, M C

    1993-04-01

    Growth hormone (GH) and insulinlike growth factor I (IGF-I) may be part of a neuroendocrine immune axis that stimulates cellular proliferation of primary lymphoid organs (bone marrow, thymus) as well as stimulates activation of peripheral lymphocytes and macrophages to enhance specific immune responses. GH can also stimulate production of thymic hormones and cytokines, and in this way impact on immune function. It is not clear whether GH and IGF-I act independently or whether the action of GH is mediated by local production of IGF-I by lymphocytes. Both GH and IGF-I and their receptors are present in lymphocytes. Thus, cells of the immune system may be important targets of the GH-IGF-I axis. PMID:18407143

  7. 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.

  8. A polymorphism in the leptin receptor gene at position 223 is associated with growth hormone replacement therapy responsiveness in idiopathic short stature and growth hormone deficiency patients.

    PubMed

    Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh

    2012-12-01

    We hypothesized that responses to growth hormone (GH) therapy by idiopathic short stature (ISS) and growth hormone deficiency (GHD) patients were associated with single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients and forty healthy age-and gender-matched children. They were genotyped for the LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical and laboratory variables were determined before and after 2 years of GH treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a significantly higher height velocity (cm/y) than ISS patients with the G/G genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher weight velocity than patients with the G/G genotype before GH treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher body weight, higher height velocity before treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher weight velocity before treatment, but a significantly lower weight velocity was found at 2 years after GH treatment. These results suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement therapy in ISS and GHD patients. PMID:23009903

  9. Characterization of pituitary growth hormone and its receptor in the green iguana (Iguana iguana).

    PubMed

    Ávila-Mendoza, José; Carranza, Martha; Pérez-Rueda, Ernesto; Luna, Maricela; Arámburo, Carlos

    2014-07-01

    Pituitary growth hormone (GH) has been studied in most vertebrate groups; however, only a few studies have been carried out in reptiles. Little is known about pituitary hormones in the order Squamata, to which the green iguana (gi) belongs. In this work, we characterized the hypophysis of Iguana iguana morphologically. The somatotrophs (round cells of 7.6-10 μm containing 250- to 300-nm secretory granules where the giGH is stored) were found, by immunohistochemistry and in situ hybridization, exclusively in the caudal lobe of the pars distalis, whereas the lactotrophs were distributed only in the rostral lobe. A pituitary giGH-like protein was obtained by immuno-affinity chromatography employing a heterologous antibody against chicken GH. giGH showed molecular heterogeneity (22, 44, and 88 kDa by SDS-PAGE/Western blot under non-reducing conditions and at least four charge variants (pIs 6.2, 6.5, 6.9, 7.4) by isoelectric focusing. The pituitary giGH cDNA (1016 bp), amplified by PCR and RACE, encodes a pre-hormone of 218 aa, of which 190 aa correspond to the mature protein and 28 aa to the signal peptide. The giGH receptor cDNA was also partially sequenced. Phylogenetic analyses of the amino acid sequences of giGH and giGHR homologs in vertebrates suggest a parallel evolution and functional relationship between the GH and its receptor. PMID:24769041

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Human growth hormone doping in sport

    PubMed Central

    Saugy, M; Robinson, N; Saudan, C; Baume, N; Avois, L; Mangin, P

    2006-01-01

    Background and objectives Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. Methods Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. Results and conclusion The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half‐life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays. PMID:16799101

  16. 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

  17. 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

  18. 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.

  19. Transient partial growth hormone deficiency due to zinc deficiency.

    PubMed

    Nishi, Y; Hatano, S; Aihara, K; Fujie, A; Kihara, M

    1989-04-01

    We present here a 13-year-old boy with partial growth hormone deficiency due to chronic mild zinc deficiency. When zinc administration was started, his growth rate, growth hormone levels, and plasma zinc concentrations increased significantly. His poor dietary intake resulted in chronic mild zinc deficiency, which in turn could be the cause of a further loss of appetite and growth retardation. There was also a possibility of renal zinc wasting which may have contributed to zinc deficiency. Zinc deficiency should be carefully ruled out in patients with growth retardation. PMID:2708733

  20. 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

  1. Growth hormone deficiency during young adulthood and the benefits of growth hormone replacement

    PubMed Central

    Ahmid, M; Perry, C G; Ahmed, S F

    2016-01-01

    Until quite recently, the management of children with growth hormone deficiency (GHD) had focussed on the use of recombinant human GH (rhGH) therapy to normalise final adult height. However, research over the past two decades that has demonstrated deficits in bone health and cardiac function, as well as impaired quality of life in adults with childhood-onset GHD (CO-GHD), has questioned this practice. Some of these studies suggested that there may be short-term benefits of rhGH in certain group of adolescents with GHD during transition, although the impact of GHD and replacement during the transition period has not been adequately investigated and its long-term benefits remain unclear. GH therapy remains expensive and well-designed long-term studies are needed to determine the cost effectiveness and clinical benefit of ongoing rhGH during transition and further into adulthood. In the absence of compelling data to justify widespread continuation of rhGH into adult life, there are several questions related to its use that remain unanswered. This paper reviews the effects of growth hormone deficiency on bone health, cardiovascular function, metabolic profile and quality of life during transition and young adulthood. PMID:27129699

  2. 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

  3. 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. PMID:22494952

  4. 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

  5. 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

  6. Growth hormone responses to growth hormone-releasing hormone in Hand-Schüller-Christian Disease.

    PubMed

    Gelato, M C; Loriaux, D L; Merriam, G R

    1989-09-01

    Bolus doses of GH-releasing hormone (GHRH), 1 microgram/kg i.v., were given to two groups of adult patients with growth hormone deficiency (GHD): 9 with Hand-Schüller-Christian disease (HSCD, presumed hypothalamic GHD) and 9 with idiopathic GHD (IGHD, etiology unknown). Six patients in each group were then given further GHRH doses daily for 5 days, and the GH responses to GHRH were measured over 3 h on day 1 and day 5. Plasma levels of insulin-like growth factor-I (IGF-I) were measured twice daily on days 1 and 5 during GHRH treatment. All patients with HSCD had measurable GH responses to the first dose of GHRH, with a mean peak response of 6.4 +/- 2.1 ng/ml (mean +/- SE). Only 5 of 9 patients with IGHD had GH responses above the detection limits of the assay; their mean peak response, 1.3 +/- 0.2 ng/ml, was significantly lower than the GH responses of the HSCD patients (p less than 0.05). Responses in both groups of patients were lower than those previously observed in normal adult men (35 +/- 8 ng/ml; p less than 0.01). Five days of daily stimulation with GHRH significantly (p less than 0.01) increased the GH response in both groups of patients. The rise was greater in patients with HSCD than with IGHD (HSCD, 5.1 +/- 2.5 ng/ml on day 1, vs. 12.0 +/- 6.8 ng/ml on day 5; IGHD, 1.4 +/- 0.3 ng/ml vs. 2.9 +/- 0.6 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2507952

  7. Intestinal hormones and growth factors: Effects on the small intestine

    PubMed Central

    Drozdowski, Laurie; Thomson, Alan BR

    2009-01-01

    There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In partI, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part II will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids. PMID:19152442

  8. 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.

  9. [Growth hormone deficiency in the adult: only an endocrinologic problem?].

    PubMed

    Martini, Chiara; Maffei, Pietro; De Carlo, Eugenio; Mioni, Roberto; Sicolo, Nicola; Scandellari, Cesare

    2002-01-01

    In the literature published during the last decade an increased risk of death due to cerebrovascular and cardiovascular events in growth hormone deficient adults has been reported. A partial reversibility of the syndrome following recombinant growth hormone treatment has also been described. Both these factors have contributed to the proposal of growth hormone therapy not only for children but also for adults. Following the initial enthusiasm, the scientific community is now evaluating various clinical experiences held over recent years and weighing up the results. Present day medicine has to take the economic impact of prescribed therapeutic regimens into consideration; in other words the ratio between cost and benefits must be calculated. The relatively recent issuance of the license for the treatment of growth hormone deficiency in adults using recombinant growth hormone does not allow us to evaluate a possible reduction in the risk of death due to cerebrovascular and cardiovascular events in treated subjects. A much longer observational period will be required. Besides the partial reversibility of the syndrome as a consequence of treatment, it is necessary to single out the selection criteria for the choice of treatment. These could also be useful as indicators of the efficacy of the same treatment. PMID:12402662

  10. 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

  11. 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.

  12. 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.

  13. Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

    PubMed Central

    Oberbauer, A. M.; German, J. B.; Murray, J. D.

    2016-01-01

    In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE2 and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (ste-aroyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis. PMID:21442273

  14. [News options and preparations in growth hormone therapy].

    PubMed

    Aguiar-Oliveira, Manuel H; Meneguz-Moreno, Rafael A; Nascimento-Junior, Adão C

    2008-07-01

    In the last twenty years, recombinant human Growth hormone (hrGH) has been available for the treatment of Growth Hormone Deficiency (GHD) in children and more recently in adults. However, the necessity of daily injections compromises the patient's compliance. Attempts to improve this compliance includes the use of pens and needle free devices, once the infusion pumps, not always physiologic, are of restricted use. When growth is the purpose of treatment, daily subcutaneous hrGH is still the most indicated. Nevertheless the expansion of GH replacement to new uses and especially in adults will need new preparations. Nowadays, the oral secretagogues have not proved efficacy to be used in clinical practice and the slow- release preparations of GH and GH releasing hormone that could improve the patient's compliance will need to be studied considering long term efficacy and safety. PMID:18797599

  15. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    PubMed Central

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. The mean age at onset of the disease was 3.2 years and at investigation 10.7 years. The average attained height equalled -0.3 SD at onset, and -1.0 SD at the time of investigation. Secretion of growth hormone was substantially reduced compared with controls and did not increase during puberty. A prompt rise in growth hormone secretion was seen after injection of growth hormone releasing hormone, but the mean maximum growth hormone concentration was, however, only 25 mU/l. There was no correlation between the 24 hour secretion and growth hormone response to growth hormone releasing hormone, or the time since irradiation. These results confirm earlier work that suggested that girls who had received treatment for acute lymphoblastic leukaemia, that included cranial irradiation, have a comparative growth hormone insufficiency characterised by normal prepubertal growth and slow growth during puberty because of an inability to respond to the increased demands for growth hormone at that time. PMID:2494952

  16. Growth hormone receptors in the atherinid Odontesthes bonariensis: characterization and expression profile after fasting-refeeding and growth hormone administration.

    PubMed

    Botta, P E; Simó, I; Sciara, A A; Arranz, S E

    2016-05-01

    In order to improve the understanding of pejerrey Odontesthes bonariensis, growth hormone (Gh)-insulin-like growth factor-1(Igf1) axis, O. bonariensis growth hormone receptor type 1 (ghr1) and type 2 (ghr2) mRNA sequences were obtained. Both transcripts were ubiquitously expressed except in kidney, encephalon and anterior intestine. Alternative transcripts of both receptors were found in muscle. Interestingly, two different ghr2 transcripts with alternative polyadenylation (APA) sites located in the long 3' untranslated region (UTR-APA) were also found in liver. Hepatic ghr1, ghr2 and insulin-like growth factor type 1 (igf1) transcript levels were examined under two different metabolic conditions. In the first experimental condition, fish were fasted for 2 weeks and then re-fed for another 2 weeks. Despite igf1 mRNA relative expression did not show significant differences under the experimental period of time examined, both ghr transcripts decreased their expression levels after the fasting period and returned to their control levels after re-feeding. In the second treatment, recombinant O. bonariensis growth hormone (r-pjGh) was orally administered once a week. After 4 weeks of treatment, liver igf1, ghr1 and ghr2 mRNA relative expression increased (13, 4·5 and 2·1 fold, P < 0·05) compared to control values. These results add novel information to the growth hormone-insulin-like growth factor system in teleosts. PMID:27097742

  17. 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.

  18. 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.

  19. 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

  20. [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. PMID:24485161

  1. Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in two cases without growth hormone deficiency.

    PubMed

    Austin, Devon E; Gunn, Alistair J; Jefferies, Craig A

    2015-02-01

    Wolf-Hirschhorn syndrome (WHS) is a rare congenital disorder occurring in approximately 1/50 000 births, with marked pre- and postnatal growth failure. WHS results from the hemizygous deletion encompassing the 4p16.3 region. This report of two children with WHS shows that growth hormone treatment in selected children with WHS and severe short stature may have a substantial effect on long-term growth. PMID:25988083

  2. Risk assessment of growth hormones and antimicrobial residues in meat.

    PubMed

    Jeong, Sang-Hee; Kang, Daejin; Lim, Myung-Woon; Kang, Chang Soo; Sung, Ha Jung

    2010-12-01

    Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented. PMID:24278538

  3. Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat

    PubMed Central

    Jeong, Sang-Hee; Kang, Daejin; Lim, Myung-Woon; Kang, Chang Soo

    2010-01-01

    Growth promoters including hormonal substances and antibiotics are used legally and illegally in food producing animals for the growth promotion of livestock animals. Hormonal substances still under debate in terms of their human health impacts are estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA) . Many of the risk assessment results of natural steroid hormones have presented negligible impacts when they are used under good veterinary practices. For synthetic hormonelike substances, ADIs and MRLs have been established for food safety along with the approval of animal treatment. Small amounts of antibiotics added to feedstuff present growth promotion effects via the prevention of infectious diseases at doses lower than therapeutic dose. The induction of antimicrobial resistant bacteria and the disruption of normal human intestinal flora are major concerns in terms of human health impact. Regulatory guidance such as ADIs and MRLs fully reflect the impact on human gastrointestinal microflora. However, before deciding on any risk management options, risk assessments of antimicrobial resistance require large-scale evidence regarding the relationship between antimicrobial use in food-producing animals and the occurrence of antimicrobial resistance in human pathogens. In this article, the risk profiles of hormonal and antibacterial growth promoters are provided based on recent toxicity and human exposure information, and recommendations for risk management to prevent human health impacts by the use of growth promoters are also presented. PMID:24278538

  4. 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

  5. Growth hormone stimulation test - series (image)

    MedlinePlus

    ... anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on ... of hGH indicates a problem either in the hypothalamus or the pituitary. Additional testing can illustrate the ...

  6. 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. PMID:26905653

  7. 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 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  8. Growth hormone in the eye: A comparative update.

    PubMed

    Harvey, Steve; Martínez-Moreno, Carlos G; Ávila-Mendoza, José; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    Comparative studies have previously established that the eye is an extrapituitary site of growth hormone (GH) production and action in fish, amphibia, birds and mammals. In this review more recent literature and original data in this field are considered. PMID:26828817

  9. Recombinant truncated tilapia growth hormone enhances growth and innate immunity in tilapia fry (Oreochromis sp.).

    PubMed

    Acosta, Jannel; Carpio, Yamila; Besada, Vladimir; Morales, Reynold; Sánchez, Aniel; Curbelo, Yosvel; Ayala, Julio; Estrada, Mario P

    2008-05-15

    Pichia pastoris cells transformed with a plasmid engineered for the expression of tilapia growth hormone as a secreted product produced a proteolytically cleaved form of the recombinant protein. The sequence of this truncated variant was obtained by mass spectrometry analysis. The cleavage site was determined to be between residues Tyr 158 and Tyr 159. The resulting truncated tilapia growth hormone was a single chain protein lacking 46 amino acids of the C-terminal portion. In this study, we showed that the truncated growth hormone produced in the P. pastoris culture supernatant has growth promoting effects and stimulates innate immune parameters (lysozyme and lectins) in tilapia larvae. These results suggest that the C-terminal portion of growth hormone is not required for its growth promoting activity and the innate immune functions studied herein in fish. In addition, we found that the culture supernatant containing truncated tilapia growth hormone has a stronger effect over growth and immune system than cells lysate containing intact tilapia growth hormone expressed in P. pastoris. PMID:18471813

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

    PubMed

    Kasuya, Etsuko

    2016-02-01

    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

  11. 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.

  12. 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.

  13. 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 ...

  14. An examination of the effects of different doses of recombinant human growth hormone on children with growth hormone deficiency

    PubMed Central

    XUE, YING; GAO, YIQING; WANG, SHUQIN; WANG, PEI

    2016-01-01

    The aim of the present study was to examine the effects of different doses of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and on thyroid and glucose metabolism to identify more reasonable therapeutic doses of growth hormone (GH) for the treatment of this condition. In total, 60 prepubertal patients with GHD were randomly divided into the high-dose and low-dose groups (n=30 per group). The groups were treated with 0.1 or 0.05 U/kg for 6 months, respectively. The follow-up study focused on changes to the serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein (IGFBP)-3, blood glucose, thyroid hormone [triiodothyronine (T3) and its prohormone, thyroxine (T4), and thyroid stimulating hormone (TSH)] and the analysis of variance of the repeated data. Changes in the height, body weight and bone age of the high-dose group were greater than those of the low-dose group. After 6 months of treatment, the difference in height between the two groups was statistically significant (P<0.05). Glucose metabolism in the two groups was consistent, but there was a statistically significant difference in the fasting blood glucose (FBG) levels of the two groups after 6 months of treatment (P<0.05). Prior to treatment, the T3, T4 and TSH values (the thyroid function tests) in the two groups, especially for the value of T3 in high-dose group were varied. However, 6 months after treatment, statistically significant differences between the two groups (P<0.05) were identified. In conclusion, 0.1 U/kg of GH is beneficial to children with GHD in attaining a satisfactory height, but it leads to insulin resistance. Thus, glucose metabolism and thyroid function should be monitored on a regular basis in a clinical setting. PMID:27168784

  15. Transplacental transfer of a growth hormone-releasing hormone peptide from mother to fetus in the rat.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies showed that when growth hormone-releasing hormone (GHRH) was administered to either pregnant rats or pigs as a plasmid-mediated therapy, pituitary weight, somatotroph and lactotroph numbers, and postnatal growth rate of the offspring increased. To determine if these responses result...

  16. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

    PubMed Central

    Chen, Zhihong; Yang, Songhe; He, Yaqiang; Song, Chengjun; Liu, Yongping

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats. PMID:25206472

  17. 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)

  18. Single nucleotide polymorphisms in intron 1 and intron 2 of Larimichthys crocea growth hormone gene are correlated with growth traits

    NASA Astrophysics Data System (ADS)

    Ni, Jing; You, Feng; Xu, Jianhe; Xu, Dongdong; Wen, Aiyun; Wu, Zhihao; Xu, Yongli; Zhang, Peijun

    2012-03-01

    The growth hormone gene ( GH) affects animal growth and is a potential target for genetic studies of variation related to growth traits. In this study, we analyzed single nucleotide polymorphisms (SNPs) in GH intron regions and their associations with growth traits in large yellow croaker, Larimichthys crocea, from Zhejiang and Fujian stocks. The results of PCR-single strand conformation polymorphism showed two haplotypes of intron 1, named AA and AB genotypes, in Zhejiang stock. AB exhibited an SNP at position 196 (G→A) that was negatively correlated with body height and positively correlated with standard length/body height ( P≤0.05). Two different genotypes, CC and CD, were identified in intron 2 in Fujian stock, with CD showing an SNP at position 692 (T→C). The CD genotype had a significantly positive correlation with both weight and total length ( P≤0.01). These basic data highlight the potential for using GH as a genetic marker of fish growth in marker assisted selection.

  19. Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer.

    PubMed

    Draghia-Akli, Ruxandra; Hahn, Kevin A; King, Glen K; Cummings, Kathleen K; Carpenter, Robert H

    2002-12-01

    Cachexia is a common manifestation of late stage malignancy and is characterized by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue. Although cachexia is disabling and can diminish the life expectancy of cancer patients, there are still no effective therapies for this condition. We have examined the feasibility of using a myogenic plasmid to express growth hormone-releasing hormone (GHRH) in severely debilitated companion dogs with naturally occurring tumors. At a median of 16 days after intramuscular delivery of the plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure of GHRH activity, were increased in 12 of 16 dogs (P < 0.01). These increases ranged from 21 to 120% (median, 49%) of the pretreatment values and were generally sustained or higher on the final evaluation. Anemia resolved posttreatment, as indicated by significant increases in mean red blood cell count, hematocrit, and hemoglobin concentrations, and there was also a significant rise in the percentage of circulating lymphocytes. Treated dogs maintained their weights over the 56-day study and did not show any adverse effects from the GHRH gene transfer. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of stimulating the release of growth hormone and IGF-I in large animals. The observed anabolic responses to a single dose of this therapy might be beneficial in patients with cancer-associated anemia and cachexia. PMID:12498779

  20. Thyroid Hormone Receptor Binds to a Site in the Rat Growth Hormone Promoter Required for Induction by Thyroid Hormone

    NASA Astrophysics Data System (ADS)

    Koenig, Ronald J.; Brent, Gregory A.; Warne, Robert L.; Reed Larsen, P.; Moore, David D.

    1987-08-01

    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.

  1. 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.

  2. 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.

  3. Promotion of melanoma growth by the metabolic hormone leptin.

    PubMed

    Ellerhorst, Julie A; Diwan, A H; Dang, Shyam M; Uffort, Deon G; Johnson, Marilyn K; Cooke, Carolyn P; Grimm, Elizabeth A

    2010-04-01

    We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells. PMID:20204272

  4. Growth hormone releasing factor-like immunoreactivity in human milk.

    PubMed

    Werner, H; Amarant, T; Fridkin, M; Koch, Y

    1986-03-28

    The presence of immunoreactive growth hormone-releasing factor (GRF) in human milk has been demonstrated. By using sequential high performance liquid chromatography, it has been shown that most of the immunoreactivity co-elutes with the synthetic, hypothalamic-like, GRF (1-40). The concentrations of GRF detected (between 152 and 432 pg GRF/ml milk) exceed several fold its values in plasma. PMID:3083812

  5. Rat growth-hormone release stimulators from fenugreek seeds.

    PubMed

    Shim, Sang Hee; Lee, Eun Ju; Kim, Ju Sun; Kang, Sam Sik; Ha, Hyekyung; Lee, Ho Young; Kim, Chungsook; Lee, Je-Hyun; Son, Kun Ho

    2008-09-01

    Bioassay-guided fractionation of MeOH extract from fenugreek (Trigonella foenum-graecum L.) seeds resulted in the isolation of two rat growth-hormone release stimulators in vitro, fenugreek saponin I (1) and dioscin (9), along with two new, i.e., 2 and 3, and five known analogues, i.e., 4-8. The structures of the new steroidal saponins, fenugreek saponins I, II, and III (1-3, resp.), were determined as gitogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, sarsasapogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, and gitogenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside, respectively. Fenugreek saponin I (1) and dioscin (9) caused ca. 12.5- and 17.7-fold stimulation of release, respectively, of rat growth hormone from rat pituitary cells, whereas gitogenin (5) showed moderate activity. To our knowledge, this is the first study to demonstrate that steroidal saponins stimulate rat growth-hormone release in rat pituitary cells. PMID:18816528

  6. Growth hormone, enhancement and the pharmaceuticalisation of short stature.

    PubMed

    Morrison, Michael

    2015-04-01

    This paper takes the biological drug human Growth Hormone (hGH) as a case study to investigate processes of pharmaceuticalisation and medicalisation in configuring childhood short stature as a site for pharmaceutical intervention. Human growth hormone is considered to have legitimate applications in treating childhood growth hormone deficiency and short stature associated with other recognised conditions. It is also regarded by bioethicists and others as a form of human biomedical enhancement when applied to children with idiopathic or 'normal' short stature. The purpose of this study is not to evaluate whether treatment of idiopathic short stature is enhancement or not, but to evaluate how some applications of hGH in treating short stature have come to be accepted and stabilised as legitimate 'therapies' while others remain contested as 'enhancements'. A comparative, historical approach is employed, drawing on approaches from medical sociology and Science and Technology Studies (STS) to set out a socio-technical history of hGH in the US and UK. Through this history the relative influence and interplay of drivers of pharmaceuticalisation, including industry marketing and networks of drug distribution, and processes of medicalisation will be employed to address this question and simultaneously query the value of enhancement as a sociological concept. PMID:25455477

  7. Constant amplitude and post-overload fatigue crack growth behavior in PM aluminum alloy AA 8009

    NASA Technical Reports Server (NTRS)

    Reynolds, A. P.

    1991-01-01

    A recently developed, rapidly solidified, powder metallurgy, dispersion strengthened aluminum alloy, AA 8009, was fatigue tested at room temperature in lab air. Constant amplitude/constant delta kappa and single spike overload conditions were examined. High fatigue crack growth rates and low crack closure levels compared to typical ingot metallurgy aluminum alloys were observed. It was proposed that minimal crack roughness, crack path deflection, and limited slip reversibility, resulting from ultra-fine microstructure, were responsible for the relatively poor da/dN-delta kappa performance of AA 8009 as compared to that of typical IM aluminum alloys.

  8. Constant amplitude and post-overload fatigue crack growth behavior in PM aluminum alloy AA 8009

    NASA Technical Reports Server (NTRS)

    Reynolds, A. P.

    1992-01-01

    A recently developed, rapidly solidified, powder metallurgy, dispersion strengthened aluminum alloy, AA 8009, was fatigue tested at room temperature in lab air. Constant amplitude/constant delta kappa and single spike overload conditions were examined. High fatigue crack growth rates and low crack closure levels compared to typical ingot metallurgy aluminum alloys were observed. It was proposed that minimal crack roughness, crack path delection, and limited slip reversibility, resulting from ultra-fine microstructure, were responsible for the relatively poor da/dN-delta kappa performance of AA 8009 as compared to that of typical IM aluminum alloys.

  9. Measurements of prolactin and growth hormone synthesis and secretion by rat pituitary cells in culture.

    PubMed

    Gautvik, K M; Kriz, M

    1976-02-01

    A specific and sensitive immunoprecipitation method for measurements of biosynthesized radioactive prolactin and growth hormone is described. Antisera to rat prolactin and growth hormone were developed in the rabbit and monkey, respectively. The specificity of the immune sera was assessed by polyacylamide gel electrophoresis of the dissolved immunoprecipitates. The two antisera showed cross-reactions with the nonhomologous hormone of less than 1%. Separation of tritium-labelled prolactin and growth hormone by immunoprecipitation, followed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate was shown to be 95-57% complete. When both hormones were measured in the same microsample by sequential immunoprecipitation, the reaction was 97% complete for determination of intra- and extracellular prolactin and extracellular growth hormone, but 85% complete for determination of intracellular growth hormone. This method has been used to characterize the basal synthesis and secretion of prolactin and growth hormone in three different but related, pituitary cell strains. Radioactive prolactin and growth hormone was obtained from monolayer cultures when the cells were grown in the presence of [3H]L-leucine. The rate of prolactin synthesis and extracellular accumulation was higher than that of growth hormone in a cell strain which produced both hormones. In these cells prolactin synthesis represents 1-5%, and growth hormone 0.1-0.6% of total protein synthesis. PMID:942913

  10. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    SciTech Connect

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

  11. 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.

  12. Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes

    PubMed Central

    Palmiter, Richard D.; Brinster, Ralph L.; Hammer, Robert E.; Trumbauer, Myrna E.; Rosenfeld, Michael G.; Birnberg, Neal C.; Evans, Ronald M.

    2016-01-01

    A DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone was microinjected into the pronuclei of fertilized mouse eggs. Of 21 mice that developed from these eggs, seven carried the fusion gene and six of these grew significantly larger than their littermates. Several of these transgenic mice had extraordinarily high levels of the fusion mRNA in their liver and growth hormone in their serum. This approach has implications for studying the biological effects of growth hormone, as a way to accelerate animal growth, as a model for gigantism, as a means of correcting genetic disease, and as a method of farming valuable gene products. PMID:6958982

  13. Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

    PubMed Central

    Torres-Aleman, I; Redding, T W; Schally, A V

    1985-01-01

    The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy. PMID:2858096

  14. Regulation of Growth Hormone by the Splanchnic Area.

    PubMed

    Barja-Fernandez, Silvia; Folgueira, Cintia; Castelao, Cecilia; Leis, Rosaura; Crujeiras, Ana B; Casanueva, Felipe F; Seoane, Luisa M

    2016-01-01

    The regulation of growth hormone (GH) was traditionally thought to be under the control of two main hypothalamic neuropeptides; GH-releasing hormone and somatostatin. In 1999, with the isolation of ghrelin, as a gastric-derived peptide with potent GH-releasing activity, concept of regulation of the somatotropic axis completely changed. In addition to its GH-releasing activity, ghrelin exhibited the capacity to modulate food intake and body weight. The role of this splanchnic factor in regulating GH as a nexus of energy balance control and GH are explored in this chapter. From a physiological standpoint, a novel mechanism of GH regulation mediated by ghrelin exists, implicating the peripheral modulation of the cannabinoid receptor. PMID:26940386

  15. Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma.

    PubMed

    Jukes, Alistair; Allan, Rodney; Rawson, Robert; Buckland, Michael E

    2016-09-01

    Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7-15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called 'collision tumour'. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis. PMID:27068013

  16. Discovery of growth hormone-releasing hormones and receptors in nonmammalian vertebrates

    PubMed Central

    Lee, Leo T. O.; Siu, Francis K. Y.; Tam, Janice K. V.; Lau, Ivy T. Y.; Wong, Anderson O. L.; Lin, Marie C. M.; Vaudry, Hubert; Chow, Billy K. C.

    2007-01-01

    In mammals, growth hormone-releasing hormone (GHRH) is the most important neuroendocrine factor that stimulates the release of growth hormone (GH) from the anterior pituitary. In nonmammalian vertebrates, however, the previously named GHRH-like peptides were unable to demonstrate robust GH-releasing activities. In this article, we provide evidence that these GHRH-like peptides are homologues of mammalian PACAP-related peptides (PRP). Instead, GHRH peptides encoded in cDNAs isolated from goldfish, zebrafish, and African clawed frog were identified. Moreover, receptors specific for these GHRHs were characterized from goldfish and zebrafish. These GHRHs and GHRH receptors (GHRH-Rs) are phylogenetically and structurally more similar to their mammalian counterparts than the previously named GHRH-like peptides and GHRH-like receptors. Information regarding their chromosomal locations and organization of neighboring genes confirmed that they share the same origins as the mammalian genes. Functionally, the goldfish GHRH dose-dependently activates cAMP production in receptor-transfected CHO cells as well as GH release from goldfish pituitary cells. Tissue distribution studies showed that the goldfish GHRH is expressed almost exclusively in the brain, whereas the goldfish GHRH-R is actively expressed in brain and pituitary. Taken together, these results provide evidence for a previously uncharacterized GHRH-GHRH-R axis in nonmammalian vertebrates. Based on these data, a comprehensive evolutionary scheme for GHRH, PRP-PACAP, and PHI-VIP genes in relation to three rounds of genome duplication early on in vertebrate evolution is proposed. These GHRHs, also found in flounder, Fugu, medaka, stickleback, Tetraodon, and rainbow trout, provide research directions regarding the neuroendocrine control of growth in vertebrates. PMID:17283332

  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. Expression of Growth Hormone Genes in Transgenic Mice

    PubMed Central

    Palmiter, Richard D.; Hammer, Robert E.; Brinster, Ralph L.

    2016-01-01

    OVERVIEW Human or rat growth hormone (GH) genes have been introduced into all cells of a mouse by microinjection of fertilized eggs but they were not expressed under their own promoters. However, substitution of a mouse metallothionein (MT) promoter allowed expression and regulation comparable to that of the endogenous MT genes. These fusion genes have been used to stimulate the growth of both normal mice and dwarf mice that lack sufficient GH. Substitution of a rat elastase-I promoter directed expression of GH exclusively to the acinar cells of the pancreas. Progress has been made towards developing the hGH gene into a vector that is not expressed in vivo unless an enhancer element is inserted. Recombination between overlapping DNA fragments derived from a MThGH gene, each of which is nonfunctional, has been observed when they are coinjected into mouse eggs. In some cases, functional hGH was produced as evidenced by enhanced growth of the mice.

  19. 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. PMID:26540761

  20. 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

  1. 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.

  2. Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

    PubMed

    Cheng, Jing-min; Gu, Jian-wen; Kuang, Yong-qin; Ma, Yuan; Xia, Xun; Yang, Tao; Lu, Min; He, Wei-qi; Sun, Zhi-yong; Zhang, Yan-chao

    2015-03-01

    The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications. PMID:25403160

  3. [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. PMID:23746703

  4. Growth hormone and ocular dysfunction: Endocrine, paracrine or autocrine etiologies?

    PubMed

    Harvey, Steve; Martinez-Moreno, Carlos G

    2016-08-01

    The eye is a target site for GH action and growth hormone has been implicated in diabetic retinopathy and other ocular dysfunctions. However, while this could reflect the hypersecretion of pituitary GH, the expression of the GH gene is now known to occur in ocular tissues and it could thus also reflect excess GH production within the eye itself. The possibility that ocular dysfunctions might arise from endocrine, autocrine or paracrine etiologies of GH overexpression is therefore the focus of this brief review. PMID:27082451

  5. 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

  6. 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.

  7. 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.

  8. Identification of Growth Hormone Receptor in Plexiform Neurofibromas of Patients with Neurofibromatosis Type 1

    PubMed Central

    Cunha, Karin Soares Gonçalves; Barboza, Eliane Porto; da Fonseca, Eliene Carvalho

    2008-01-01

    OBJECTIVE The aim of this study was to investigate the presence of growth hormone receptor in plexiform neurofibromas of neurofibromatosis type 1 patients. INTRODUCTION The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. A recent study showed that the majority of localized neurofibromas from neurofibromatosis type 1 patients have growth hormone receptor. METHODS Growth hormone receptor expression was investigated in 5 plexiform neurofibromas using immunohistochemistry. RESULTS Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. CONCLUSION This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1. PMID:18297205

  9. 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.

  10. 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.

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

    PubMed Central

    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. PMID:26204839

  12. Evolution of Growth Hormone Devices: Matching Devices with Patients.

    PubMed

    Raimer-Hall, Dawn; Shea, Heidi Chamberlain

    2015-01-01

    Self-injection of growth hormone (GH) by children with GH deficiency can be problematic. They may have difficulty manipulating injection devices or preparing medication, and injections can be painful and create anxiety. Adherence to daily GH injections optimizes treatment benefit. Studies indicate that injection pens or needle-free devices enable easy self-injection by children, minimize medication reconstitution and storage requirements, and reduce injection pain. Newer GH delivery devices potentially encourage improved patient adherence. Reviewing features of GH devices will help nurses decide which GH device best fits the needs and abilities of pediatric patients. We searched recent medical literature about GH device development, about device-associated patient preferences and treatment adherence, and comparisons among GH devices. We concluded that improved awareness of the strengths and limitations of GH devices will enable nurses to guide families in selecting and using GH devices, improving adherence and outcomes, and helping children reach full growth potential. PMID:26292454

  13. Aging and immune function: a possible role for growth hormone.

    PubMed

    Gelato, M C

    1996-01-01

    Elderly individuals have four to five times the case rate of cancer, tuberculosis and herpes zoster and six to seven times the fatality rate from pneumonia compared to young adults. This may be causally related to two changes that occur with aging, i.e. decreased growth hormone (GH)/insulin-like growth factor-1 (IGF-1) production and decreased immune function. Data from our laboratory as well as others have shown that, based on either GH secretory dynamics or IGF-1 levels, approximately 40% of adults aged 60 and older are GH deficient. In the same population of subjects, immune function decreases such that there is a decline in cell-mediated and humoral immune responsiveness. Some of these immune deficits have been shown to be reversed in humans and primates by GH and/or IGF-1 treatment. This paper will review some of these data. PMID:8742118

  14. Psychological response to growth hormone treatment in short normal children.

    PubMed Central

    Downie, A B; Mulligan, J; McCaughey, E S; Stratford, R J; Betts, P R; Voss, L D

    1996-01-01

    This study provides a controlled assessment of the psychological (and physical) effects of growth hormone treatment. Fifteen short 'normal' children (height SD score < -2) have been treated with growth hormone since the age of 7/8 years. They, together with untreated short controls and average controls (10th-90th centiles), were assessed at recruitment, after three years, and after five years. Only the treated group showed a significant height increase (SD score -2.44 to -1.21 over five years). No significant differences were found at recruitment, three years, or five years in IQ, attainment, behaviour, or self esteem. Also at five years, there were no significant differences in locus of control, self perception, or parental perceptions of competence. Both short groups displayed less satisfaction with their height than the controls (p < 0.01), though all groups were optimistic of being tall adults. The treated children were no more unrealistic over final height than the untreated children. To date, no psychological benefits of treatment have been demonstrated; but nor have there been any discernible ill effects for either the treated or the untreated children. PMID:8813867

  15. Prader-Willi Syndrome and Growth Hormone Deficiency

    PubMed Central

    Aycan, Zehra; Baş, Veysel Nijat

    2014-01-01

    Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient’s life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures. PMID:24932597

  16. 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

  17. 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…

  18. 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

  19. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

    PubMed Central

    Katakami, H; Downs, T R; Frohman, L A

    1986-01-01

    The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and intracellular cyclic AMP accumulation to GRH, while somatostatin (SRIF) suppressive effects on GH secretion were increased. Hypothalamic GRH content was also markedly reduced. T4Rx completely restored hypothalamic GRH content and spontaneous GH secretion despite only partial recovery of pituitary GH content, GRH and SRIF sensitivity, and intracellular cyclic AMP response to GRH. The results indicate multiple effects of hypothyroidism on GH secretion and suggest that a critical role of T4 in maintaining normal GH secretion, in addition to restoring GH synthesis, is related to its effect on hypothalamic GRH. Images PMID:2871046

  20. 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

  1. 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

  2. Long-term effects of plasmid-mediated growth hormone releasing hormone in dogs.

    PubMed

    Tone, Catherine M; Cardoza, Dawn M; Carpenter, Robert H; Draghia-Akli, Ruxandra

    2004-05-01

    Geriatric and cancer-afflicted patients often experience decreased quality of life with cachexia, anemia, anorexia, and decreased activity level. We have studied the possibility that a myogenic plasmid that expresses growth hormone releasing hormone (GHRH) can prevent and/or treat these conditions. We administered plasmid to 17 geriatric and five cancer-afflicted companion dogs with an average age of 10.5+/-1.0 and 11.3+/-0.6 years at enrollment, respectively. Effects of the treatment were documented for at least 180 days post-treatment, with 10 animals followed for more than 1 year post-treatment, on average 444+/-40 days. Treated dogs showed increased IGF-I levels, and increases in scores for weight, activity level, exercise tolerance, and appetite. No adverse effects associated with the GHRH plasmid treatment were found. Most importantly, the overall assessment of the quality of life of the treated animals increased. Hematological parameters such as red blood cell count, hematocrit, and hemoglobin concentrations were improved and maintained within their normal ranges. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of improving the quality of life in animals for an extended period of time in the context of aging and disease. The observed anabolic and hematological responses to a single dose of this plasmid treatment may also be beneficial in geriatric patients or patients with cancer-associated anemia and/or cachexia. PMID:15073611

  3. 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

  4. 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). PMID:26075039

  5. Effect of hypophysectomy and growth hormone replacement on hypothalamic growth hormone-releasing factor messenger ribonucleic Acid levels.

    PubMed

    Eccleston, L M; Powell, J F; Clayton, R N

    1991-12-01

    Abstract The mechanisms by which the pituitary gland, and growth hormone (GH) in particular, affect growth hormone-releasing factor (GRF) gene expression have been addressed using the technique of in situ hybridization. Anatomically matched sections through the mediobasal hypothalamus of control and hypophysectomized male rats, with or without GH hormone replacement, were analysed to obtain information on GRF mRNA levels within the arcuate nucleus and around the ventromedial hypothalamus. Hypophysectomy resulted in a 70% increase in the amount of GRF mRNA per cell (P<0.001), within neurons in the arcuate nucleus. GH replacement and T4 replacement separately partially attenuated this increase (GH replacement P< 0.001 versus hypophysectomy, T4 replacement P<0.05 versus hypophysectomy). Additionally, after hypophysectomy there was an 80% increase in the number of cells expressing the GRF gene in neurons around the ventromedial hypothalamus, when compared to shamoperated controls (P<0.01). Both GH and T4 replacement separately partially attenuated this phenomenon (P<0.01 versus hypophysectomized animals). Hypothyroidism alone did not affect GRF mRNA levels in either the arcuate nucleus or in the area surrounding the ventromedial hypothalamus. These results show that hypophysectomy increases GRF mRNA levels in two separate ways: by increasing the amount of mRNA produced per cell within the arcuate nucleus, and by increasing the number of cells expressing the gene in the area surrounding the ventromedial hypothalamus. This increase in the number of GRF mRNA-containing cells after hypophysectomy could result from the recruitment of neurons which previously did not express the GRF gene, and may reflect the plasticity of the adult central nervous system in response to a changing endocrine environment. This could represent part of a sensor mechanism to drive the production of GRF in the arcuate nucleus in response to extreme disruption of the GRF/ GH feedback loop. PMID

  6. 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.

  7. 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

  8. 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. PMID:25957918

  9. 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...

  10. Lipopeptide antagonists of growth hormone-releasing hormone with improved antitumor activities.

    PubMed

    Zarandi, Marta; Varga, Jozsef L; Schally, Andrew V; Horvath, Judit E; Toller, Gabor L; Kovacs, Magdolna; Letsch, Markus; Groot, Kate; Armatis, Patricia; Halmos, Gabor

    2006-03-21

    Antagonists of growth hormone-releasing hormone (GHRH) synthesized previously inhibit proliferation of various human cancers, but derivatisation with fatty acids could enhance their clinical efficacy. We synthesized a series of antagonists of GHRH(1-29)NH(2) acylated at the N terminus with monocarboxylic or alpha,omega-dicarboxylic acids containing six to sixteen carbon atoms. These peptides are analogs of prior potent antagonists JV-1-36, JV-1-38, and JV-1-65 with phenylacetyl group at their N terminus. Several new analogs, including MZ-J-7-46 and MZ-J-7-30, more effectively inhibited GHRH-induced GH release in vitro in a superfused rat pituitary system than their parent compound JV-1-36 and had increased binding affinities to rat pituitary GHRH receptors, but they showed weaker inhibition of GH release in vivo than JV-1-36. All antagonists acylated with fatty acids containing 8-14 carbon atoms inhibited the proliferation of MiaPaCa-2 human pancreatic cancer cells in vitro better than JV-1-36 or JV-1-65. GHRH antagonist MZ-J-7-114 (5 mug/day) significantly suppressed the growth of PC-3 human androgen-independent prostate cancers xenografted into nude mice and reduced serum IGF-I levels, whereas antagonist JV-1-38 had no effect at the dose of 10 mug/day. GHRH antagonists including MZ-J-7-46 and MZ-J-7-114 acylated with octanoic acid and MZ-J-7-30 and MZ-J-7-110 acylated with 1,12-dodecanedicarboxylic acid represent relevant improvements over earlier antagonists. These and previous results suggest that this class of GHRH antagonists might be effective in the treatment of various cancers. PMID:16537407

  11. Lipopeptide antagonists of growth hormone-releasing hormone with improved antitumor activities

    PubMed Central

    Zarandi, Marta; Varga, Jozsef L.; Schally, Andrew V.; Horvath, Judit E.; Toller, Gabor L.; Kovacs, Magdolna; Letsch, Markus; Groot, Kate; Armatis, Patricia; Halmos, Gabor

    2006-01-01

    Antagonists of growth hormone-releasing hormone (GHRH) synthesized previously inhibit proliferation of various human cancers, but derivatisation with fatty acids could enhance their clinical efficacy. We synthesized a series of antagonists of GHRH(1-29)NH2 acylated at the N terminus with monocarboxylic or α,ω-dicarboxylic acids containing six to sixteen carbon atoms. These peptides are analogs of prior potent antagonists JV-1-36, JV-1-38, and JV-1-65 with phenylacetyl group at their N terminus. Several new analogs, including MZ-J-7-46 and MZ-J-7-30, more effectively inhibited GHRH-induced GH release in vitro in a superfused rat pituitary system than their parent compound JV-1-36 and had increased binding affinities to rat pituitary GHRH receptors, but they showed weaker inhibition of GH release in vivo than JV-1-36. All antagonists acylated with fatty acids containing 8–14 carbon atoms inhibited the proliferation of MiaPaCa-2 human pancreatic cancer cells in vitro better than JV-1-36 or JV-1-65. GHRH antagonist MZ-J-7-114 (5 μg/day) significantly suppressed the growth of PC-3 human androgen-independent prostate cancers xenografted into nude mice and reduced serum IGF-I levels, whereas antagonist JV-1-38 had no effect at the dose of 10 μg/day. GHRH antagonists including MZ-J-7-46 and MZ-J-7-114 acylated with octanoic acid and MZ-J-7-30 and MZ-J-7-110 acylated with 1,12-dodecanedicarboxylic acid represent relevant improvements over earlier antagonists. These and previous results suggest that this class of GHRH antagonists might be effective in the treatment of various cancers. PMID:16537407

  12. 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.

  13. 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.

  14. 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. PMID:26408965

  15. 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. PMID:26187188

  16. Parents’ views on growth hormone treatment for their children: psychosocial issues

    PubMed Central

    van Dongen, Nadine; Kaptein, Ad A

    2012-01-01

    Background We evaluated the opinions of parents in The Netherlands concerning treatment of their children with growth hormone, and examined beliefs and perceptions about treatment and quality of health care communication and support. Methods An Internet survey was completed by 69 parents who had children prescribed growth hormone and were part of the Patient Intelligence Panel. Acceptance of the diagnosis and treatment was investigated with reference to four topics, ie, search and quality of information, involvement in decision-making process, operational aspects, and emotional problems and support. Results Among the parents surveyed, 48% reported a lack of freedom to choose the type of growth hormone device that best suited their needs, 92% believed that their children (and they themselves) would benefit if the children self-administered growth hormone, and 65% believed training to support self-administration would be helpful. According to 79%, the availability of support from another parent with experience of treating their own child with growth hormone, alongside their doctor, would be valuable. Thirty-seven percent of the parents indicated that their children felt anxious about administration of growth hormone, and 83% of parents would appreciate psychological support to overcome their anxiety. An increase in reluctance to receive treatment with growth hormone was observed by 40% of parents after the children reached puberty, and 57% of these parents would appreciate psychological support to overcome this reluctance. Conclusion Understanding how growth hormone treatments and their implications are perceived by parents is a first step towards addressing quality of growth hormone treatment, which may be instrumental in improving adherence. The data show a need for support and involvement of parents in the process of choosing a growth hormone device. This decision-making process may be instrumental in improving acceptance and diminishing emotional problems for

  17. Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytes

    SciTech Connect

    Foster, C.M.; Shafer, J.A.; Rozsa, F.W.; Wang, X.; Lewis, S.D.; Renken, D.A.; Natale, J.E.; Schwartz, J.; Carter-Su, C.

    1988-01-12

    Because many growth factor receptors are ligand-activated tyrosine protein kinases, the possibility that growth hormone (GH), a hormone implicated in human growth, promotes tyrosyl phosphorylation of its receptor was investigated. /sup 125/I-Labeled human GH was covalently cross-linked to receptors in intact 3T3-F442A fibroblasts, a cell line which differentiates into adipocytes in response to GH. The cross-linked cells were solubilized and passed over a column of phosphotyrosyl binding antibody immobilized on protein A-Sepharose. Immunoadsorbed proteins were eluted with a hapten (p-nitrophenyl phosphate) and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The eluate from the antibody column contained in M/sub r/ 134,000 /sup 125/I-GH-receptor complex. A similar result was obtained when the adipocyte form of 3T3-F442A cells was used in place of fibroblast form. O-Phosphotyrosine prevented /sup 125/I-GH-receptor complexes from binding to the antibody column, whereas O-phosphoserine and O-phosphothreonine did not. In studies of GH-promoted phosphorylation in 3T3-F442A fibroblasts labeled metabolically with (/sup 32/P)P/sub i/, GH was shown to stimulate formation of a /sup 32/P-labeled protein which bound to immobilized phosphotyrosyl binding antibodies. The molecular weight of 114,000 obtained for this protein is similar to that expected for non-cross-linked GH receptor. These observations provide strong evidence that binding of GH to its receptor stimulates phosphorylation of tyrosyl residues in the GH receptor.

  18. 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...

  19. Diverse growth hormone receptor gene mutations in Laron syndrome

    SciTech Connect

    Berg, M.A.; Francke, U. ); Gracia, R.; Rosenbloom, A.; Toledo, S.P.A. ); Chernausek, S. ); Guevara-Aguirre, J. ); Hopp, M. ); Rosenbloom, A.; Argente, J. ); Toledo, S.P.A. )

    1993-05-01

    To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), the authors analysed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. They amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). They identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71+1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, they determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. The authors conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. 35 refs., 3 figs., 1 tab.

  20. Growth hormone treatment in pediatric burns: a safe therapeutic approach.

    PubMed Central

    Ramirez, R J; Wolf, S E; Barrow, R E; Herndon, D N

    1998-01-01

    OBJECTIVE: To determine the safety and efficacy of recombinant human growth hormone (rhGH) in the treatment of children who are severely burned. SUMMARY BACKGROUND DATA: During the last decade, we have used recombinant human growth hormone (rhGH; 0.2 mg/kg/day s.q.) to successfully treat 130 children with more than 40% total body surface area (TBSA) burns to enhance wound healing and decrease protein loss. A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH has recently been reported in two large European trials which questions the therapeutic safety of rhGH. METHODS: The records of 263 children who were burned were reviewed. Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a randomized clinical trial (n = 48) or therapeutically (n = 82) were compared with randomized placebo-administered controls (n = 54), contiguous matched controls (n = 48), and matched patients admitted after August 1997, after which no patients were treated with rhGH (n = 31). Morbidity and mortality, which might be altered by rhGH therapy, were considered with specific attention to organ function or failure, infection, hemodynamics, and calcium, phosphorous, and albumin balance. RESULTS: A 2% mortality was observed in both rhGH and saline placebo groups in the controlled studies, with no differences in septic complications, organ dysfunction, or heart rate pressure product identified. In addition, no difference in mortality could be shown for those given rhGH therapeutically versus their controls. No patient deaths were attributed to rhGH in autopsies reviewed by observers blinded to treatment. Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients, whereas exogenous albumin requirements and the development of hypocalcemia was reduced. CONCLUSIONS: Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious. PMID:9790334

  1. 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

  2. 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, ...

  3. 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

  4. Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

    PubMed

    Bahrami, A; Behzadi, Sh; Miraei-Ashtiani, S R; Roh, S-G; Katoh, K

    2013-09-15

    The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies. PMID:23747407

  5. Polymorphisms of the porcine cathepsins, growth hormone-releasing hormone and leptin receptor genes and their association with meat quality traits in Ukrainian Large White breed.

    PubMed

    Balatsky, Viktor; Bankovska, Irina; Pena, Ramona N; Saienko, Artem; Buslyk, Tetyana; Korinnyi, Sergii; Doran, Olena

    2016-06-01

    Cathepsins, growth hormone-releasing hormone (GHRH) and leptin receptor (LEPR) genes have been receiving increasing attention as potential markers for meat quality and pig performance traits. This study investigated the allele variants in four cathepsin genes (CTSB, CTSK, CTSL, CTSS), GHRH and LEPR in pure-bred Ukrainian Large White pigs and evaluated effects of the allele variants on meat quality characteristics. The study was conducted on 72 pigs. Genotyping was performed using PCR-RFLP technique. Meat quality characteristics analysed were intramuscular fat content, tenderness, total water content, ultimate pH, crude protein and ashes. A medium level of heterozygosity values was established for GHRH and LEPR genes which corresponded to very high levels of informativeness indexes. Cathepsins CTSL, CTSB and CTSK had a low level of heterozygosity, and CTSS did not segregate in this breed. Association studies established that intramuscular fat content and tenderness were affected by the allele variance in GHRH and LEPR but not by CTSB and CTSL genes. The GHRH results could be particularly relevant for the production of lean prime cuts as the A allele is associated with both, a lower meat fat content and better tenderness values, which are two attributes highly regarded by consumers. Results of this study suggest that selective breeding towards GHRH/AA genotype would be particularly useful for improving meat quality characteristics in the production systems involving lean Large White lines, which typically have less than 2 % intramuscular fat content. PMID:27075656

  6. Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema

    PubMed Central

    Lucas, Rudolf; Sridhar, Supriya; Rick, Ferenc G.; Gorshkov, Boris; Umapathy, Nagavedi S.; Yang, Guang; Oseghale, Aluya; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Zemskov, Evgeny A.; White, Richard; Block, Norman L.; Schally, Andrew V.

    2012-01-01

    Aggressive treatment with antibiotics in patients infected with Streptococcus pneumoniae induces release of the bacterial virulence factor pneumolysin (PLY). Days after lungs are sterile, this pore-forming toxin can still induce pulmonary permeability edema in patients, characterized by alveolar/capillary barrier dysfunction and impaired alveolar liquid clearance (ALC). ALC is mainly regulated through Na+ transport by the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed Na+/K+-ATPase in type II alveolar epithelial cells. Because no standard treatment is currently available to treat permeability edema, the search for novel therapeutic candidates is of high priority. We detected mRNA expression for the active receptor splice variant SV1 of the hypothalamic polypeptide growth hormone-releasing hormone (GHRH), as well as for GHRH itself, in human lung microvascular endothelial cells (HL-MVEC). Therefore, we have evaluated the effect of the GHRH agonist JI-34 on PLY-induced barrier and ALC dysfunction. JI-34 blunts PLY-mediated endothelial hyperpermeability in monolayers of HL-MVEC, in a cAMP-dependent manner, by means of reducing the phosphorylation of myosin light chain and vascular endothelial (VE)-cadherin. In human airway epithelial H441 cells, PLY significantly impairs Na+ uptake, but JI-34 restores it to basal levels by means of increasing cAMP levels. Intratracheal instillation of PLY into C57BL6 mice causes pulmonary alveolar epithelial and endothelial hyperpermeability as well as edema formation, all of which are blunted by JI-34. These findings point toward a protective role of the GHRH signaling pathway in PLY-induced permeability edema. PMID:22308467

  7. 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…

  8. 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. PMID:21731659

  9. 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.

  10. 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.

  11. Growth hormone replacement in adults - current standards and new perspectives.

    PubMed

    Höybye, Charlotte; Christiansen, Jens Sandahl

    2015-01-01

    Growth hormone deficiency (GHD) in adults is an established clinical syndrome characterised by adverse body composition with more body fat than lean body mass, unfavourable blood lipids, decreased physical fitness and poor quality of life. No specific biomarker for GHD exists and the sometimes difficult diagnosis should be made in accordance with, established guidelines. Measurements of insulin-like growth factor I (IGF-I) is often not sufficient for the diagnosis and stimulation tests of the GH reserve are required. After diagnosis of GHD, treatment with GH should be initiated with a low dose, and gradually increased aiming at obtaining an IGF-I level within the upper part of the normal range for age matched healthy controls. Most side effects are mild and transient and attenuated by gradual dose increments. Numerous studies have shown that GH treatment can improve body composition, cardiovascular risk factors, physical capacity and quality of life. However, studies on effects beyond 5 years are few and despite encouraging preliminary reports the ultimate endpoint demonstrating that GH treatment has beneficial effects on mortality, cardiovascular events and fractures without an increase in cancer incidence remain to be solidly demonstrated and studies to resolve these issues are awaited. Trials with long acting GH formulations are ongoing and available data indicate similar effects on outcome measures compared to the effects of daily injections. This review will give an overview of clinically relevant issues of GHD including advice for management of these patients. PMID:25617177

  12. 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.

  13. 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.

  14. 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

  15. 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. PMID:19363508

  16. 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.

  17. 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

  18. Uncoupling of Secretion From Growth in Some Hormone Secretory Tissues

    PubMed Central

    2014-01-01

    Context: Most syndromes with benign primary excess of a hormone show positive coupling of hormone secretion to size or proliferation in the affected hormone secretory tissue. Syndromes that lack this coupling seem rare and have not been examined for unifying features among each other. Evidence Acquisition: Selected clinical and basic features were analyzed from original reports and reviews. We examined indices of excess secretion of a hormone and indices of size of secretory tissue within the following three syndromes, each suggestive of uncoupling between these two indices: familial hypocalciuric hypercalcemia, congenital diazoxide-resistant hyperinsulinism, and congenital primary hyperaldosteronism type III (with G151E mutation of the KCNJ5 gene). Evidence Synthesis: Some unifying features among the three syndromes were different from features present among common tumors secreting the same hormone. The unifying and distinguishing features included: 1) expression of hormone excess as early as the first days of life; 2) normal size of tissue that oversecretes a hormone; 3) diffuse histologic expression in the hormonal tissue; 4) resistance to treatment by subtotal ablation of the hormone-secreting tissue; 5) causation by a germline mutation; 6) low potential of the same mutation to cause a tumor by somatic mutation; and 7) expression of the mutated molecule in a pathway between sensing of a serum metabolite and secretion of hormone regulating that metabolite. Conclusion: Some shared clinical and basic features of uncoupling of secretion from size in a hormonal tissue characterize three uncommon states of hormone excess. These features differ importantly from features of common hormonal neoplasm of that tissue. PMID:25004249

  19. Hormones and Obesity: Changes in Insulin and Growth Hormone Secretion Following Surgically Induced Weight Loss

    PubMed Central

    Crockford, P. M.; Salmon, P. A.

    1970-01-01

    Ten obese patients were subjected to insulin tolerance tests (0.2 unit per kg. regular insulin intravenously) and/or treadmill exercise tolerance testing (2.6 m.p.h. at 11° angulation) before and after surgically induced weight reduction. Immunoreactive growth hormone (IRGH) responses returned to normal with weight reduction in all but one—a grossly obese woman studied relatively early in the postoperative period when still far from the ideal body weight. Five of these patients and two additional subjects had intravenous glucose tolerance tests (0.5 g. per kg.) before and after weight reduction. In all, there was a significant diminution in immunoreactive insulin (IRI) values, accompained by little or no change in the glucose disappearance rate (KG) and a significant improvement in insulin effectiveness as indicated by the calculated “insulinogenic index”. It was concluded that the abnormalities in IRGH and IRI secretion, as well as the insulin resistance in obesity, are probably secondary and not of primary importance in the etiology of this disorder. PMID:5430052

  20. 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

  1. Diabetes mellitus in a dog with a growth hormone-producing acidophilic adenoma of the adenohypophysis.

    PubMed

    van Keulen, L J; Wesdorp, J L; Kooistra, H S

    1996-07-01

    A 9-year-old male Doberman Pinscher was referred to the Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, for polyuria/polydipsia, anorexia, and vomiting. Laboratory examination of blood and urine revealed hyperglycemia, glucosuria, and acidosis. Diabetes mellitus was diagnosed but was very resistant to subsequent insulin treatment. At the owners' request, the dog was euthanatized and a postmortem examination was performed. In addition to hepatic, pancreatic, and renal changes compatible with diabetes mellitus, an acidophilic adenoma of the adenohypophysis was found. Immunohistochemical staining for growth hormone, adrenocorticotropic hormone, and prolactin showed a strong immunolabeling for growth hormone within the cytoplasm of the tumor cells. Although growth hormone level was not measured in the plasma, our findings suggest that the diabetes mellitus in this dog was caused by excess growth hormone secreted by the pituitary neoplasm. PMID:8817849

  2. Personalized approach to growth hormone treatment: clinical use of growth prediction models.

    PubMed

    Wit, J M; Ranke, M B; Albertsson-Wikland, K; Carrascosa, A; Rosenfeld, R G; Van Buuren, S; Kristrom, B; Schoenau, E; Audi, L; Hokken-Koelega, A C S; Bang, P; Jung, H; Blum, W F; Silverman, L A; Cohen, P; Cianfarani, S; Deal, C; Clayton, P E; de Graaff, L; Dahlgren, J; Kleintjens, J; Roelants, M

    2013-01-01

    The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic. PMID:23735882

  3. Growth enhancement of shrimp (Litopenaeus schmitti) after transfer of tilapia growth hormone gene.

    PubMed

    Arenal, Amilcar; Pimentel, Rafael; Pimentel, Eulogio; Martín, Leonardo; Santiesteban, Dayamí; Franco, Ramón; Aleström, Peter

    2008-05-01

    Electroporation of Litopenaeus schmitti embryos was used to transfer the pE300tiGH15 plasmid that contains the tilapia growth hormone gene (tiGH) complexed with a nuclear localization signal peptide into the zygotes. The gene construct was detected in 35 (36%) of the 98 larvae screened by PCR and Southern blot analyses. Western blot analyses revealed that 34% of the screened larvae expressed a single tiGH-specific band with the expected molecular mass (23.1 kDa). The development index and larval length indicated a significant growth enhancement from day 3 on after electroporation, with an average of 32% of the growth enhancement. To our knowledge, this is the first report on gene transfer enhanced growth in crustaceans. PMID:18204820

  4. 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

  5. Difference in growth hormone response to growth hormone-releasing hormone (GHRH) testing following GHRH subacute treatment in normal aging and growth hormone-deficient adults: possible perspectives for therapeutic use of GHRH or its analogs in elderly subjects?

    PubMed

    Iovino, M; Triggiani, V; Giagulli, V A; Iovine, N; Licchelli, B; Resta, F; Sabbà, C; Tafaro, E; Solimando, A; Tommasicchio, A; Guastamacchia, E

    2011-06-01

    The somatotroph axis function shows a decline in the elderly (somatopause). In particular growth hormone (GH) response to GH-releasing hormone (GHRH) is reduced in aged man but less than that observed in GH-deficient adults (GHDAs). Plasma GH response to GHRH (1 µg/kg BW) was significantly lower in four GHDAs than in seven healthy aged men 30, 60, and 90 min after acute GHRH administration. To verify whether a priming regimen might be able to increase the reduced GH response to GHRH, both healthy aged men and GHDA patients underwent repetitive administration of GHRH (100 µg GHRH intravenously as a single morning dose, every 2 days for 12 days). After the GHRH-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points before priming regimen in healthy aged men but not in GHDA patients. These findings confirmed that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response only in healthy aged men but not in GHDA patients. This could support the possible use of GHRH or its analogs instead of recombinant human GH in elderly patients with the advantage of preserving the endogenous pulses of GH with the secretion of the different isoforms of GH. However, concerns arise about the possible role of these molecules in tumorigenesis and tumor growth promotion. PMID:20843274

  6. Growth hormone prevents the development of autoimmune diabetes.

    PubMed

    Villares, Ricardo; Kakabadse, Dimitri; Juarranz, Yasmina; Gomariz, Rosa P; Martínez-A, Carlos; Mellado, Mario

    2013-11-26

    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. 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

  8. 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.

  9. 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.

  10. 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).

  11. Growth hormone secretion during sleep in male depressed patients.

    PubMed

    Sakkas, P N; Soldatos, C R; Bergiannaki, J D; Paparrigopoulos, T J; Stefanis, C N

    1998-04-01

    1. Growth hormone (GH) secretion during sleep was studied in ten male patients with major depression according to DSM III and eight normal controls. 2. Samples were collected through a continuous blood withdrawal pump while sleep was recorded in the laboratory. 3. The results showed a marked decrease in the GH secretion mainly during the first three hours of sleep in depressed patients as compared to normal controls. DST and TRH tests were also administered to the same patients but no correlation was observed between a positive test and a blunted GH secretion, suggesting that the various neuroendocrinological disturbances do not coexist in all depressed patients. 4. This disturbance in GH secretion during sleep, along with reduced slow wave sleep (SWS), gives support to the theory that GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and its counterpart CRH plays a major role in the pathophysiology of disturbed endocrine activity during sleep in depression. PMID:9612844

  12. 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

  13. Progestin-induced hypersecretion of growth hormone: an introductory review.

    PubMed

    Rijnberk, A; Mol, J A

    1997-01-01

    In the 1970s acromegalic features were reported in some dogs used in long-term toxicity studies of progestins. In 1980 confirmation that progestagen administration can lead to increased circulating growth hormone (GH) concentrations was obtained. This phenomenon appeared not to be confined to exogenous progestins, for an excess of GH was also found in bitches during the luteal phase of the oestrous cycle. In bitches with a progestin-induced excess of GH, GH secretion could neither be inhibited nor stimulated by well-known regulatory neurohormones, indicating autonomous secretion. Because it could not be attributed to a neoplasm and was reversible, an extra-pituitary site of GH production was investigated. The progestin-induced GH was found to originate from the mammary gland. This phenomenon seems to play a role in the mammary development that occurs during the luteal phase of the oestrous cycle. The increase in cell proliferative activity may also be responsible for the susceptibility of the mammary gland to neoplastic transformation. The discovery of mammary GH in the dog has recently become of wider importance now that expression of the GH gene has also been demonstrated in other species, namely, humans and cats. PMID:9404303

  14. Molecular basis of human growth hormone gene deletions.

    PubMed Central

    Vnencak-Jones, C L; Phillips, J A; Chen, E Y; Seeburg, P H

    1988-01-01

    Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained within a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment. Images PMID:2840669

  15. Sleep disturbance in children with growth hormone deficiency.

    PubMed

    Hayashi, M; Shimohira, M; Saisho, S; Shimozawa, K; Iwakawa, Y

    1992-05-01

    We examined the effects of growth hormone (GH) deficiency on sleep development by performing all-night polysomnography in three female children with GH deficiency (GHD). The percentage of REM sleep seemed to be reduced before the treatment in 2 cases, and human GH (hGH) compensation slightly increased it. Submental twitch movements (mTMs), i.e., body movements during sleep localized in the submental muscle and lasting less than 0.5 seconds, were commonly disturbed in the three patients. Rapid eye movements in REM sleep (REMs) were reduced before the therapy in one case, this decrease being reversed on hGH compensation. REMs also seemed to increase after hGH treatment in the other two cases. Dopamines and cholinergic muscarinic agonists can cause GH release, while mTMs and REMs might be related to dopaminergic and cholinergic systems in the human brain. It is intriguing that GHD, and the disturbance of mTMs and REMs coexisted in children with GHD. Since a relatively poor social outcome in patients with GHD has been reported, even after hGH compensation, it is important to monitor their neurological development by means of evaluation of their sleep disturbance. PMID:1445594

  16. 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

  17. ACSL4 promotes prostate cancer growth, invasion and hormonal resistance.

    PubMed

    Wu, Xinyu; Deng, Fangming; Li, Yirong; Daniels, Garrett; Du, Xinxin; Ren, Qinghu; Wang, Jinhua; Wang, Ling Hang; Yang, Yang; Zhang, Valerio; Zhang, David; Ye, Fei; Melamed, Jonathan; Monaco, Marie E; Lee, Peng

    2015-12-29

    Increases in fatty acid metabolism have been demonstrated to promote the growth and survival of a variety of cancers, including prostate cancer (PCa). Here, we examine the expression and function of the fatty acid activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), in PCa. Ectopic expression of ACSL4 in ACSL4-negative PCa cells increases proliferation, migration and invasion, while ablation of ACSL4 in PCa cells expressing endogenous ACSL4 reduces cell proliferation, migration and invasion. The cell proliferative effects were observed both in vitro, as well as in vivo. Immunohistochemical analysis of human PCa tissue samples indicated ACSL4 expression is increased in malignant cells compared with adjacent benign epithelial cells, and particularly increased in castration-resistant PCa (CRPC) when compared with hormone naive PCa. In cell lines co-expressing both ACSL4 and AR, proliferation was independent of exogenous androgens, suggesting that ACSL4 expression may lead to CRPC. In support for this hypothesis, ectopic ACSL4 expression induced resistance to treatment with Casodex, via decrease in apoptosis. Our studies further indicate that ACSL4 upregulates distinct pathway proteins including p-AKT, LSD1 and β-catenin. These results suggest ACSL4 could serve as a biomarker and potential therapeutic target for CRPC. PMID:26636648

  18. β-Blockade and Growth Hormone After Burn

    PubMed Central

    Hart, David W.; Wolf, Steven E.; Chinkes, David L.; Lal, Sofia O.; Ramzy, Peter I.; Herndon, David N.

    2002-01-01

    Objective To determine whether propranolol and growth hormone (GH) have additive effects to combat burn-induced catabolism. Summary Background Data Both GH and propranolol have been attributed anabolic properties after severe trauma and burn. It is conceivable that the two in combination would have additive effects. Methods Fifty-six children with more than 40% TBSA burns were randomized to one of four anabolic regimens: untreated control, GH treatment, propranolol treatment, or combination GH plus propranolol therapy. Clinical treatment was identical for all groups. Resting energy expenditure was determined by indirect calorimetry and skeletal muscle protein kinetics were measured using stable amino acid isotope infusions before and after each anabolic regimen. Results There were no differences in age, sex, or burn size between groups. Tachycardia and energy expenditure were decreased during propranolol treatment (P < .05). The net balance of muscle protein synthesis and breakdown was improved during proprandol and GH plus propranolol treatment (P < .05). There was no significant benefit of GH alone. No additive effect of combination therapy was seen. Conclusions Propranolol is a strongly anabolic drug during the early, hypercatabolic period after burn. No synergistic effect between propranolol and GH was identified. PMID:12368673

  19. 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

    2015-01-01

    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

  20. Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

    PubMed

    Gunn, Katherine C; Cutfield, Wayne S; Hofman, Paul L; Jefferies, Craig A; Albert, Benjamin B; Gunn, Alistair J

    2014-01-01

    In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from -1.9 (-3.6, -0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment. PMID:25317732

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells

    NASA Astrophysics Data System (ADS)

    Morgan, Jeffrey R.; Barrandon, Yann; Green, Howard; Mulligan, Richard C.

    1987-09-01

    Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.

  7. 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. PMID:17281277

  8. Effect of growth hormone on ribonucleic acid metabolism. The template activity of the chromatin and molecular species of ribonucleic acid synthesized after treatment with the hormone

    PubMed Central

    Gupta, S. L.; Talwar, G. P.

    1968-01-01

    Growth hormone stimulates the synthesis of RNA in hypophysectomized rat liver. The question whether the hormonal stimulation of RNA synthesis is due to the activation of repressed cistrons or to other factors was studied. Nuclear RNA from the livers of adult female hypophysectomized and growth-hormone-treated rats was examined for molecular homology by hybridization techniques: no new species of RNA were detected after hormone treatment. The template activity of the chromatin for RNA synthesis is also not increased by the action of growth hormone. Short- and long-pulse-labelling experiments demonstrate that the hormonal stimulation of RNA synthesis is most marked in experiments where the period of incorporation of radioactive precursors is limited to 1–2hr. It is concluded that the hormone influences essentially the rate of RNA synthesis in these tissues. PMID:5701666

  9. Pseudotumor Cerebri in a Child with Idiopathic Growth Hormone Insufficiency Two Months after Initiation of Recombinant Human Growth Hormone Treatment.

    PubMed

    Loukianou, Eleni; Tasiopoulou, Anastasia; Demosthenous, Constantinos; Brouzas, Dimitrios

    2016-01-01

    Purpose. To report a rare case of pseudotumor cerebri (PTC) in a child two months after receiving treatment with recombinant human growth hormone (rhGH) and to emphasize the need of close collaboration between ophthalmologists and pediatric endocrinologists in monitoring children receiving rhGH. Methods. A 12-year-old boy with congenital hypothyroidism started treatment with rhGH on a dose of 1,5 mg/daily IM (4.5 IU daily). Eight weeks later, he was complaining of severe headache without any other accompanying symptoms. The child was further investigated with computed tomography scan and lumbar puncture. Results. Computed tomography scan showed normal ventricular size and lumbar puncture revealed an elevated opening pressure of 360 mm H2O. RhGH was discontinued and acetazolamide 250 mg per os twice daily was initiated. Eight weeks later, the papilledema was resolved. Conclusions. There appears to be a causal relationship between the initiation of treatment with rhGH and the development of PTC. All children receiving rhGH should have a complete ophthalmological examination if they report headache or visual disturbances shortly after the treatment. Discontinuation of rhGH and initiation of treatment with acetazolamide may be needed and regular follow-up examinations by an ophthalmologist should be recommended. PMID:26966604

  10. Pseudotumor Cerebri in a Child with Idiopathic Growth Hormone Insufficiency Two Months after Initiation of Recombinant Human Growth Hormone Treatment

    PubMed Central

    Loukianou, Eleni; Tasiopoulou, Anastasia; Demosthenous, Constantinos; Brouzas, Dimitrios

    2016-01-01

    Purpose. To report a rare case of pseudotumor cerebri (PTC) in a child two months after receiving treatment with recombinant human growth hormone (rhGH) and to emphasize the need of close collaboration between ophthalmologists and pediatric endocrinologists in monitoring children receiving rhGH. Methods. A 12-year-old boy with congenital hypothyroidism started treatment with rhGH on a dose of 1,5 mg/daily IM (4.5 IU daily). Eight weeks later, he was complaining of severe headache without any other accompanying symptoms. The child was further investigated with computed tomography scan and lumbar puncture. Results. Computed tomography scan showed normal ventricular size and lumbar puncture revealed an elevated opening pressure of 360 mm H2O. RhGH was discontinued and acetazolamide 250 mg per os twice daily was initiated. Eight weeks later, the papilledema was resolved. Conclusions. There appears to be a causal relationship between the initiation of treatment with rhGH and the development of PTC. All children receiving rhGH should have a complete ophthalmological examination if they report headache or visual disturbances shortly after the treatment. Discontinuation of rhGH and initiation of treatment with acetazolamide may be needed and regular follow-up examinations by an ophthalmologist should be recommended. PMID:26966604

  11. Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion.

    PubMed

    Crist, D M; Kraner, J C

    1990-12-01

    Using double-blind, placebo-controlled procedures, the effects of methionyl-human growth hormone (met-hGH) on the tumor cytotoxic activity of natural killer (NK) cells were studied in seven healthy adults using a repeated measures experiment. Subjects were assigned at random to either a placebo (bacteriostatic water) treatment condition or a met-hGH (16.0 mg/wk of Protropin) treatment condition, then crossed-over to the alternative treatment. Treatments were delivered on alternate days (3 d/wk) for 6 weeks. Without bias from the met-hGH treatment, there was no evidence for GH hyposecretion as measured by the peak circulating GH response to exercise stimulation (14.1 +/- 3.1 ng/mL) or insulin-like growth factor (IGF-I) levels (0.82 +/- 0.09 U/mL). When compared with placebo, met-hGH induced a significant overall increase in the percent specific lysis (%SL) of K562 tumor target cells (placebo 22.2 +/- 1.7 v met-hGH 28.5 +/- 2.1 %SL; P = .008). NK activity was increased within the first week of treatment and this level was maintained throughout the remaining period of supplementation. There was a trend (P = .057) for the met-hGH-induced percent change in NK activity (NK%) to be inversely related to placebo IGF-I levels (r = -.761), while there were significant positive correlations between NK% and the met-hGH-induced percent changes in IGF-I (r = .727; P = .035), the fat-free mass (FFM)/fat mass (FM) ratio derived by hydrodensitometry (r = .792; P = .012), and the endogenous GH response to exercise (r = .469; P = .034).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2246974

  12. Pharmacokinetics and pharmacodynamics of recombinant human growth hormone by subcutaneous jet- or needle-injection in patients with growth hormone deficiency.

    PubMed

    Houdijk, E C; Herdes, E; Delemarre-Van de Waal, H A

    1997-12-01

    Eighteen growth hormone (GH) deficient children and adolescents (11 6/12-20 9/12 y) participated in a randomized open, two-period (4 weeks) cross-over study to evaluate the pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) administered daily, either by subcutaneous jet-injection or conventional needle-injection. Plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), glucose, insulin, HbAlc and serum-free fatty acids (FFA) levels were analysed repeatedly. GH absorption characteristics, expressed as AUC(0-infinity), Cmax and Tmax ratio (%) jet-injected over needle-injected were similar in both groups. IGF-I and IGFBP-3 plasma levels were identical in both groups. Serum FFA concentrations were comparable after GH administration with either injection device. Surprisingly nocturnal blood glucose decreased to asymptomatic hypoglycaemic levels in all patients. The results of this study showed equal responses concerning absorption and bioavailability of growth hormone administered daily for 4 weeks by either a jet- or a needle-injection device in GH-deficient children and adolescents. PMID:9475305

  13. Hormones

    MedlinePlus

    ... the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal ...

  14. 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

  15. Overtrained horses alter their resting pulsatile growth hormone secretion

    PubMed Central

    de Graaf-Roelfsema, E.; Veldhuis, P. P.; Keizer, H. A.; van Ginneken, M. M. E.; van Dam, K. G.; Johnson, M. L.; Barneveld, A.; Menheere, P. P. C. A.; van Breda, E.; Wijnberg, I. D.; van der Kolk, J. H.

    2009-01-01

    The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern. PMID:19494168

  16. 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

  17. Thermodynamic characterization of an intermediate state of human growth hormone.

    PubMed Central

    Gomez-Orellana, I.; Variano, B.; Miura-Fraboni, J.; Milstein, S.; Paton, D. R.

    1998-01-01

    The thermal denaturation of recombinant human growth hormone (rhGH) was studied by differential scanning calorimetry and circular dichroism spectroscopy (CD). The thermal unfolding is reversible only below pH 3.5, and under these conditions a single two-state transition was observed between 0 and 100 degrees C. The magnitudes of the deltaH and deltaCp of this transition indicate that it corresponds to a partial unfolding of rhGH. This is also supported by CD data, which show that significant secondary structure remains after the unfolding. Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of rhGH upon unfolding. This aggregation is prevented in aqueous solutions of alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol), which suggests that the self-association of rhGH is caused by hydrophobic interactions. In addition, it was found that the native state of rhGH is stable in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or 30% at pH 3) and that under these conditions the thermal unfolding is cooperative and corresponds to a transition from the native state to a partially folded state, as observed at acidic pH in the absence of alcohols. In higher concentrations of propylene glycol, the tertiary structure of rhGH is disrupted and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data indicate that a partially folded intermediate with essentially native secondary structure and disordered tertiary structure becomes significantly populated in 70-80% propylene glycol. PMID:9655339

  18. Growth of PEO ceramic coatings on AA 2024-T3 aluminium alloy

    NASA Astrophysics Data System (ADS)

    Forero Sotomonte, S.; Blanco Pinzon, C.; García Vergara, S.

    2016-02-01

    The growth of PEO ceramic coatings on AA 2024-T3 aluminium alloy in an aqueous Na2SiO3 (10.5g/l), KOH (2.8g/l) solution at 310 and 400V for 500 and 710s, was investigated. The morphology, roughness and thickness of the coatings were determined by SEM, digital microscopy, XRD diffraction analysis and thickness measuring instrument. The results show that thicker coatings are produced with longer process times and high applied voltages. Due to the nature of the PEO process, the roughness of the surface coatings increases as the coating become thicker, due to the development of sparks. The coatings are porous, with a crater like morphology and they are mainly amorphous.

  19. Lymphocyte subset distribution and natural killer activity in growth hormone deficiency before and during short-term treatment with growth hormone releasing hormone.

    PubMed

    Kiess, W; Malozowski, S; Gelato, M; Butenand, O; Doerr, H; Crisp, B; Eisl, E; Maluish, A; Belohradsky, B H

    1988-07-01

    Natural killer (NK) cell activity was assessed in the peripheral blood of 20 patients with growth hormone (GH) deficiency due to a hypothalamic deficit of GH-releasing hormone (GHRH). All patients failed to respond to at least two provocative tests of GH secretion (GH below 7 ng/ml) but responded to a single GHRH iv bolus injection (1 microgram/kg body wt). In 14 of the 20 patients (20 determinations), lymphocyte subsets were also measured; in all patients the distribution of lymphocyte subsets was within the normal range. More importantly, NK cell activity in the 20 patients was significantly lower than in controls (P less than 0.01). To assess the in vivo effect of GH and GHRH on NK activity and lymphocyte subset distribution, immunologic tests were performed (i) before and after a single iv bolus injection of GHRH (1 microgram/kg body wt) in six patients; (ii) before and after 3 weeks of GHRH treatment (3-9 micrograms/kg body wt, one to four times daily) in five patients; and (iii) after 6 weeks of GH treatment (5 IU sc every alternate day) in one patient. Neither NK activity nor the distribution of lymphocyte subsets was altered during short-term GHRH administration. In conclusion, low NK activity is found in GH-deficient patients, and short-term administration of GH or GHRH fails to restore this immunological abnormality. This result suggests that the hypothalamus may be a regulator of NK activity in the human and that patients with hypothalamic deficiencies should be monitored for the development of discrete immunodeficiencies. PMID:3133146

  20. Information for People Treated with Human Growth Hormone (Comprehensive Report)

    MedlinePlus

    ... I help with the follow-up study? How did Creutzfeldt-Jakob disease (CJD) occur in people treated ... help to clarify individual level of risk. [ Top ] Did the hormone I took cause CJD? We have ...

  1. 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

  2. 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.

  3. 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.

  4. Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Okano, Masato; Sato, Mitsuhiko; Ikekita, Ayako; Kageyama, Shinji

    2010-07-30

    GHRP-2 (pralmorelin, D-Ala-D-(beta-naphthyl)-Ala-Ala-Trp-D-Phe-Lys-NH(2)), which belongs to a class of growth hormone secretagogue (GHS), is intravenously used to diagnose growth hormone (GH) deficiency. Because it may be misused in expectation of a growth-promoting effect by athletes, the illicit use of GHS by athletes has been prohibited by the World Anti-Doping Agency (WADA). Therefore, the mass spectrometric identification of urinary GHRP-2 and its metabolite D-Ala-D-(beta-naphthyl)-Ala-Ala-OH (AA-3) was studied using liquid chromatography/electrospray ionization tandem mass spectrometry for doping control purposes. The method consists of solid-phase extraction using stable-isotope-labeled GHRP-2 as an internal standard and subsequent ultra-performance liquid chromatography/tandem mass spectrometry, and the two target peptides were determined at urinary concentrations of 0.5-10 ng/mL. The recoveries ranged from 84 to 101%, and the assay precisions were calculated as 1.6-3.8% (intra-day) and 1.9-4.3% (inter-day). Intravenous administration of GHRP-2 in ten male volunteers was studied to demonstrate the applicability of the method. In all ten cases, unchanged GHRP-2 and its specific metabolite AA-3 were detected in urine. PMID:20552695

  5. The association of two single nucleotide polymorphisms (SNPs) in growth hormone (GH) gene with litter size and superovulation response in goat-breeds

    PubMed Central

    Zhang, Chunyan; Liu, Yun; Huang, Kunkun; Zeng, Wenbing; Xu, Deqing; Wen, Qunying; Yang, Liguo

    2011-01-01

    Two active mutations (A 781 G and A 1575 G) in growth hormone (GH) gene, and their associations with litter size (LS), were investigated in both a high prolificacy (Matou, n = 182) and a low prolificacy breed (Boer, n = 352) by using the PCR-RFLP method. Superovulation experiments were designed in 57 dams, in order to evaluate the effect of different genotypes of the GH gene on superovulation response. Two genotypes (AA and AB, CC and CD) in each mutation were detected in these two goat breeds. Neither BB nor DD homozygous genotypes were observed. The genotypic frequencies of AB and CC were significantly higher than those of AA and CD. In the third parity, Matou dams with AB or CC genotypes had significantly larger litter sizes than those with AA and CD (p < 0.05). On combining the two loci, both Matou and Boer dams with ABCD genotype had the largest litter sizes when compared to the other genotypes (p < 0.05). When undergoing like superovulation treatments, a significantly higher number of corpora lutea and ova, with a lower incidence of ovarian cysts, were harvested in the AB and CC genotypes than in AA and CD. These results show that the two loci of GH gene are highly associated with abundant prolificacy and superovulation response in goat breeds. PMID:21637543

  6. Bt-Cry3Aa expression reduces insect damage and improves growth in field-grown hybrid poplar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated growth and insect resistance in hybrid poplar expressing the cry3Aa gene in two field trials. An initial screening of 502 trees comprising 51 transgenic gene insertion events in four clonal backgrounds (Populus trichocarpa x P. deltoides, clones 24-305, 50-197, and 198-434; and P. d...

  7. Effects of recombinant human growth hormone in juvenile Nile crocodiles (Crocodylus niloticus).

    PubMed

    Andersen, O; Kimwele, C; Aulie, A; Kanui, T

    1990-01-01

    1. Recombinant human growth hormone (hGH) showed somatotropic activity in juvenile Nile crocodiles (Crocodylus niloticus). 2. Body weight of crocodiles receiving 3.25 micrograms hGH/g body weight twice a week was increased by 49% after five weeks of treatment, compared to 31% increase in controls. 3. Total length was increased by 15 and 5%, respectively, in the two groups. 4. Food conversion efficiency increased from 28% in the controls to 36% in the hormone injected animals. 5. Cessation of hormone treatment was followed by reduced appetite and decreasing body growth. PMID:1981037

  8. 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.

  9. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    PubMed Central

    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

  10. 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

  11. 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

  12. Impact of different concentrations of human recombinant growth hormone on T lymphocytes.

    PubMed

    Borrione, P; Grasso, L; Pautasso, M; Parisi, A; Quaranta, F; Ciminelli, E; Di Gianfrancesco, A; Di Luigi, L; Pigozzi, F

    2012-01-01

    The aim of the present study is to evaluate the effects induced by increasing concentrations of human recombinant growth hormone on T lymphocytes. Ten healthy volunteers and twelve subjects with symptomatic allergies were enrolled in the study. Peripheral blood mononuclear cells and purified T lymphocytes were cultured in the presence of graded concentrations of growth hormone. Following appropriate in vitro stimulations, the proportion of apoptotic T cells, the percentage of activated T lymphocyte subpopulations, the phytohemagglutinin responsiveness and the Th2 response were assessed by flow cytometry analysis. Moreover, in order to evaluate the phosphoinositol-3-kinase signaling pathway involvement, cells were also analyzed after treatment with LY294002. The treatment with different concentrations of growth hormone did not influence the activation pattern of un-stimulated T lymphocytes. On the contrary, growth hormone was able to modify the CD38/HLA-DR co-expression of T cells activated with phytohemoagglutinin. A different response was observed when samples obtained from healthy donors and from subjects with symptomatic allergies were analysed. Moreover, growth hormone treatment was able to increase the Th2 response in the samples obtained from healthy donors only. The results of the present study strongly support the hypothesis that growth hormone administration may play an important role in conditions of impaired/activated immune systems. The observation that growth hormone administration at high doses may reverse its effects and that it may promote a Th2-oriented response have significant clinical implications when considering the use of this hormone for artificially enhancing the physical performances of healthy athletes. PMID:22507321

  13. Hormonal regulation of rat hypothalamic neuropeptide mRNAs: effect of hypophysectomy and hormone replacement on growth-hormone-releasing factor, somatostatin and the insulin-like growth factors.

    PubMed

    Wood, T L; Berelowitz, M; Gelato, M C; Roberts, C T; LeRoith, D; Millard, W J; McKelvy, J F

    1991-03-01

    Hormonal feedback regulation of hypothalamic peptides putatively involved in growth hormone (GH) regulation has been studied by measurement of steady-state mRNA levels in male hypophysectomized rats with or without thyroid hormone, corticosterone, testosterone or GH replacement. Hypothalamic GH-releasing factor (GRF) mRNA levels increased progressively following hypophysectomy to 420% of sham levels after 15 days while hypothalamic insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) mRNA levels decreased to less than 40% of sham levels. Whole hypothalamic somatostatin mRNA levels were not significantly different from sham. One week of continuous GH infusion restored hypothalamic IGF-I mRNA to levels (95%) indistinguishable from those in sham-operated controls but had no effect on either IGF-II or GRF mRNA. Thyroid hormone, corticosterone and testosterone treatment without GH had no effect on the hypophysectomy-induced reduction of either IGF-I or IGF-II mRNA levels but reversed the elevation of GRF mRNA. We conclude that hypothalamic IGF-I may be involved in GH feedback regulation and thus may function as a hypothalamic modulator of GH. In contrast, IGF-II may be regulated by one of the pituitary trophic hormones but not by GH or the target hormones tested. Finally, hypothalamic GRF mRNA regulation appears to be complex and may include target hormone feedback. PMID:1674982

  14. Growth Hormone Releasing Hormone (GHRH) Signaling Modulates Intermittent Hypoxia-Induced Oxidative Stress and Cognitive Deficits In Mouse

    PubMed Central

    Nair, Deepti; Ramesh, Vijay; Li, Richard C.; Schally, Andrew V.; Gozal, David

    2013-01-01

    Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-OHDG, and increases in HIF-1α DNA binding and up-regulation of IGF-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. PMID:23815362

  15. 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

  16. Rooster feathering, androgenic alopecia, and hormone-dependent tumor growth: what is in common?

    PubMed

    Mayer, Julie Ann; Chuong, Cheng-Ming; Widelitz, Randall

    2004-12-01

    Different epithelial organs form as a result of epithelial-mesenchymal interactions and share a common theme modulated by variations (Chuong ed. 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 may interface 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 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. (2002) The morphogenesis of feathers. Nature 420:308-312), 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

  17. 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.

  18. 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

  19. Moral assessment of growth hormone therapy for children with idiopathic short stature.

    PubMed Central

    Verweij, M; Kortmann, F

    1997-01-01

    The prescription of growth hormone therapy for children who are not growth hormone deficient is one of the controversies in contemporary paediatric endocrinology. Is it morally appropriate to enhance the growth, by means of medical treatment, of a child wish idiopathic short stature? The medical, moral, and philosophical questions in this area are many. Data on the effects of human growth hormone (hGH) treatment will not on their own provide us with answers, as these effects have to be evaluated from a normative perspective. In this article we consider hGH treatment for children of idiopathic short stature from three normative perspectives: the goals of medicine, the good of the patient, and the public good. We argue that the prevention of psychological and social problems due to short stature (and not merely the enhancement of growth) should be the ultimate goal of medical treatment and research. PMID:9358351

  20. Effects of sex hormone disturbances on craniofacial growth in newborn mice.

    PubMed

    Fujita, T; Ohtani, J; Shigekawa, M; Kawata, T; Kaku, M; Kohno, S; Tsutsui, K; Tenjo, K; Motokawa, M; Tohma, Y; Tanne, K

    2004-03-01

    It is well-known that sex hormones influence bone metabolism. However, it remains unclear as to how sex hormones affect bone growth in newborn mice. In this study, we performed orchiectomy (ORX) and ovariectomy (OVX) on newborn mice, and examined the effects on craniofacial growth morphometrically. ORX and OVX were performed on five-day-old C57BL/6J mice. Four weeks after surgery, lateral cephalograms were taken of all of the mice, with the use of a rat and mouse cephalometer. Cephalometric analysis of the craniofacial skeleton was performed by means of a personal computer. Inhibition of craniofacial growth was found in the experimental groups but not in the sham-operated groups. In the nasomaxillary bone and mandible, the amount of growth was significantly reduced. These results suggest that craniofacial growth is inhibited by sex hormone disturbances not only in puberty but also immediately after birth. PMID:14981129

  1. Influence of Cancer-Associated Endometrial Stromal Cells on Hormone-Driven Endometrial Tumor Growth

    PubMed Central

    Pineda, M. J.; Lu, Z.; Cao, D.

    2016-01-01

    Cancer-associated fibroblasts have been shown to inhibit or stimulate tumor growth depending on stage, grade, and tumor type. It remains unclear, however, the effect of endometrial-cancer-associated fibroblasts on hormone-driven responses in endometrial cancer. In this study, we investigated the effect of normal and cancer-associated stromal cells from patients with and without endometrial cancer on endometrial tumor growth in response to estradiol (E2) and progesterone (P4). Compared to benign endometrial stromal cells, the low-grade and high-grade cancer-associated stromal cells exhibited a blunted hormone response for proliferation as well as IGFBP1 secretion. Additional analysis of the influence of stromal cells on hormone-driven tumor growth was done by mixing stromal cells from benign, low-grade, or high-grade tumors, with Ishikawa cells for subcutaneous tumor formation. The presence of both benign and high-grade cancer-associated stromal cells increased estradiol-driven xenografted tumor growth compared to Ishikawa cells alone. Low-grade cancer-associated stromal cells did not significantly influence hormone-regulated tumor growth. Addition of P4 attenuated tumor growth in Ishikawa + benign or high-grade stromal cells, but not in Ishikawa cells alone or with low-grade stromal cells. Using an angiogenesis focused real-time array TGFA, TGFB2 and TGFBR1 and VEGFC were identified as potential candidates for hormone-influenced growth regulation of tumors in the presence of benign and high-grade stromal cells. In summary, endometrial-cancer-associated cells responded differently to in vitro hormone treatment compared to benign endometrial stromal cells. Additionally, presence of stromal cells differentially influenced hormone-driven xenograft growth in vivo depending on the disease status of the stromal cells. PMID:25976290

  2. Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor

    PubMed Central

    Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Fave, Gianfranco Delle; Jensen, Robert T.

    2012-01-01

    Foregut Neuroendocrine Tumors[NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor(EGFR) by growth factors, gastrointestinal(GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGFα and various GI hormones to stimulate growth of the human foregut carcinoid, BON, the somatostatinoma QGP-1 and the rat islet tumor, Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGFα and the other growth-stimulating GI hormones increased Tyr1068 EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs. PMID:23220008

  3. Levels of hormones and cytokines associated with growth in Honamlı and native hair goats.

    PubMed

    Devrim, A K; Elmaz, O; Mamak, N; Sudagidan, M

    2015-01-01

    This study was designed to assess alterations of hormone and cytokine levels associated with growth period during puberty in Honamlı goats which were identified as a new goat breed and had one of the highest meat production potential among the other goat breeds in Turkey. Honamlı goats are originated from native hair goats, so parallel studies of sampling and analyzing were conducted also in native hair goats which have moderate meat production. Blood serum samples of Honamlı (n=90) and native hair goats (n=90) were obtained from the pure herds in Korkuteli and Ka districts of Anatolia. Concentrations of growth hormone (GH), myostatin (MSTN), insulin-like growth factor (IGF), growth hormone releasing hormone (GHRH), growth hormone releasing peptide (GHRP), leptin, transforming growth factor-betal (TGF-β1) and vascular endothelial cell growth factor (VEGF) levels were measured by ELISA in each breed in the age groups of 4, 8 and 12 months. The present results indicate interesting correlations among the age groups and all the examined hormone and cytokine parameters exhibited significant (P<0.05 and P<0.001) differences. The parameters investigated were usually begun to increase after 4 months of age in the both breeds and sexes. Therefore, this paper supported the view that the beginning of hormonal alterations of goats could occur at 4th month of age. The results reported here emphasize the primary role played by GH, MSTN, IGF-1, leptin, GHRH, GHRP, TGF-βi and VEGF in the first year growth period of goats. PMID:26172195

  4. Is the somatopause an indication for growth hormone replacement?

    PubMed

    Savine, R; Sönksen, P H

    1999-01-01

    In the normal population, a gradual and progressive fall in spontaneous growth hormone (GH) secretion occurs with increasing age and is reflected in a parallel fall in circulating insulin-like growth factor (IGF)-I, reduction in lean body mass, increase in body fat and rise in low-density lipoprotein (LDL) cholesterol. Aging is also associated with a progressive failure of body functions and particularly with an increasing lack of physical strength and mobility. Many problems of aging are attributable to the progressive loss of lean tissues and to catabolic events. This can be and often is associated with a progressive decline in independence and quality of life, leading eventually to a prolonged dependence on others, followed by a distressing process of death. By analogy with the fall in ovarian function that inevitably eventually occurs in women with increasing age, this fall in GH secretion has been termed the somatopause. In cross-sectional studies on elderly people, the amount of GH secreted spontaneously correlates well with "good risk factors" such as body composition, mobility, lipid profiles and blood pressure. The important question that these scientific facts raises is whether this fall in GH secretion with increasing years is an important physiological safety event of the normal aging process, or whether it marks the development of GH deficiency which would benefit from GH replacement. It is established that a number of the clinical features of the somatopause are shared with the syndrome of adult-onset GH deficiency and Rudman first proposed the importance of GH in maintaining health and vitality with increasing age many years ago. In 1989, GH replacement was shown to be beneficial in adults with GH deficiency, and in 1990 Rudman showed remarkably similar beneficial effects in a group of elderly men with low plasma IGF-I values, but no underlying pituitary pathology, who were administered GH. In these adults, low doses of GH increased lean body mass

  5. 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

  6. Posttranscriptional regulation of rat growth hormone gene expression: increased message stability and nuclear polyadenylation accompany thyroid hormone depletion.

    PubMed Central

    Murphy, D; Pardy, K; Seah, V; Carter, D

    1992-01-01

    In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone-depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins. Images PMID:1588960

  7. Associations of DNA polymorphisms in growth hormone and its transcriptional regulators with growth and carcass traits in two populations of Brangus bulls.

    PubMed

    Thomas, M G; Enns, R M; Shirley, K L; Garcia, M D; Garrett, A J; Silver, G A

    2007-01-01

    Sequence polymorphisms in the growth hormone (GH) gene and its transcriptional regulators, Pit-1 and Prop-1, were evaluated for associations with growth and carcass traits in two populations of Brangus bulls Chihuahuan Desert Rangeland Research Center (CDRRC, N = 248 from 14 sires) and a cooperating breeding program (COOP, N = 186 from 34 sires). Polymorphisms were SNP mutations in intron 4 (C/T) and exon V (C/G) in GH, A/G in exon VI in Pit-1, and A/G in exon III in Prop-1. In the COOP population, bulls of Pit-1 GG genotype had a significantly greater percentage of intramuscular fat than bulls of the AA or AG genotype, and bulls of the Prop-1 AA genotype had significantly greater scrotal circumference than bulls of AG or GG genotypes at ~365 days of age. Also, heterozygous genotypes for the two GH polymorphisms appeared advantageous for traits of muscularity and adiposity in the COOP population. The heterozygous genotype of GH intron 4 SNP was associated with advantages in weight gain, scrotal circumference, and fat thickness in the CDRRC population. The two GH polymorphisms accounted for >/=27.7% of the variation in these traits in the CDRRC population; however, R(2) was <5% in the COOP population. Based on haplotype analyses the two GH SNPs appeared to be in phase; the haplotype analyses also paralleled with the genotype analyses. Polymorphisms in GH and its transcriptional regulators appear to be predictors of growth and carcass traits in Brangus bulls, particularly those with heterozygous GH genotypes. PMID:17469072

  8. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia.

    PubMed

    Wang, Zongwei; Olumi, Aria F

    2011-01-01

    Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and low urinary tract symptoms (LUTS). The major endocrine aberration in connection with the metabolic syndrome is hyperinsulinemia. Insulin is an independent risk factor and a promoter of BPH. Insulin resistance may change the risk of BPH through several biological pathways. Hyperinsulinemia stimulates the liver to produce more insulin-like growth factor (IGF), another mitogen and an anti-apoptotic agent which binds insulin receptor/IGF receptor and stimulates prostate growth. The levels of IGFs and IGF binding proteins (IGFBPs) in prostate tissue and in blood are associated with BPH risk, with the regulation of circulating androgen and growth hormone. Stromal-epithelial interactions play a critical role in the development and growth of the prostate gland and BPH. Previously, we have shown that the expression of c-Jun in the fibroblastic stroma can promote secretion of IGF-I, which stimulates prostate epithelial cell proliferation through activating specific target genes. Here, we will review the epidemiologic, clinical, and molecular findings which have evaluated the relation between diabetes and development of BPH. PMID:21536370

  9. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  10. Galactopoiesis/Effects of hormones and growth factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term galactopoiesis was originally coined to describe the enhancement of an established lactation. In this sense, only exogenous somatotropin and thyroid hormones are clearly demonstrated galactopoietic agents in dairy animals. However, in a more inclusive sense, galactopoiesis has been used t...

  11. Growth promotion of red sea bream, Pagrosomus major, by oral administration of recombinant eel and salmon growth hormone

    NASA Astrophysics Data System (ADS)

    Xu, Bin; Mai, Kang-Sen; Xu, Ying-Li; Miao, Hong-Zhi; Liu, Zhen-Hui; Dong, Yong; Lan, Shan; Wang, Rao; Zhang, Pei-Jun

    2001-06-01

    Recombinant eel GH and yeast containing chinook salmon growth hormone (reGH and rcsGH) were incorporated into gelatin and sodium alginate (reGH-GS and rcsGH-GS) or polymer matrix (reGH-HP55) to protect the hormone from proteolytic cleavage in the stomach. The diets containing reGH-GS, rcsGH-GS, reGH-HP55 and free-reGH or uncoated-rcsGH were administered to red sea bream. Feeding of reGH-GS, reGH-HP55 and rcsGH-GS diets resulted in significant increases in body weight and fork length over those of controls. These results strongly suggest that gelatin and sodium alginate as well as polymer matrix protected the hormone from proteolytic enzymes in the gastrointestinal tract to allow the bioactive hormone to enter the circulation and eventually stimulate fish growth.

  12. Growth hormone and insulin-like growth factors in fish: Where we are and where to go

    USGS Publications Warehouse

    Reinecke, M.; Bjornsson, Bjorn Thrandur; Dickhoff, Walton W.; McCormick, S.D.; Navarro, I.; Power, D.M.; Gutierrez, J.

    2005-01-01

    This communication summarizes viewpoints, discussion, perspectives, and questions, put forward at a workshop on "Growth hormone and insulin-like growth factors in fish" held on September 7th, 2004, at the 5th International Symposium on Fish Endocrinology in Castello??n, Spain. ?? 2005 Elsevier Inc. All rights reserved.

  13. The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary gland development is dependent upon the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis, this same axis has also been implicated in breast cancer progression. In this study we investigated the effect of a GH antagonist, pegvisomant (Somavert((R)), Pfizer), on normal mammary gla...

  14. Growth hormone treatment in a patient with Hurler-Scheie syndrome.

    PubMed

    Rogers, Douglas G; Nasomyont, Nat

    2014-09-01

    A female patient with known Hurler-Scheie syndrome, who underwent hematopoietic cell transplantation, presented with growth retardation and delayed puberty. She started growth hormone (GH) treatment at age 12.33 years, resulting in significantly improved linear growth and predicted adult height. We describe details of her clinical course and literature review of growth pattern as well as GH use in patients with mucopolysaccharidosis I. PMID:24825081

  15. Growth hormone (GH)–releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus?

    PubMed Central

    Hersch, Elizabeth C; Merriam, George R

    2008-01-01

    Although growth hormone (GH) is primarily associated with linear growth in childhood, it continues to have important metabolic functions in adult life. Adult GH deficiency (AGHD) is a distinct clinical entity, and GH replacement in AGHD can improve body composition, strength, aerobic capacity, and mood, and may reduce vascular disease risk. While there are some hormone-related side effects, the balance of benefits and risks is generally favorable, and several countries have approved GH for clinical use in AGHD. GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial AGHD. This suggests that replacing GH, or stimulating GH with GH-releasing hormone or a GH secretagogue could confer benefits in normal aging similar to those observed in AGHD – in particular, could reduce the loss of muscle mass, strength, and exercise capacity leading to frailty, thereby prolonging the ability to live independently. However, while most GH studies have shown body composition effects similar to those in AGHD, functional changes have been much less inconsistent, and older adults are more sensitive to GH side effects. Preliminary reports of improved cognition are encouraging, but the overall balance of benefits and risks of GH supplementation in normal aging remains uncertain. PMID:18488883

  16. Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

    NASA Technical Reports Server (NTRS)

    Fiorindo, R. P.; Negulesco, J. A.

    1980-01-01

    Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

  17. Auxin, the organizer of the hormonal/environmental signals for root hair growth.

    PubMed

    Lee, Richard D-W; Cho, Hyung-Taeg

    2013-01-01

    The root hair development is controlled by diverse factors such as fate-determining developmental cues, auxin-related environmental factors, and hormones. In particular, the soil environmental factors are important as they maximize their absorption by modulating root hair development. These environmental factors affect the root hair developmental process by making use of diverse hormones. These hormonal factors interact with each other to modulate root hair development in which auxin appears to form the most intensive networks with the pathways from environmental factors and hormones. Moreover, auxin action for root hair development is genetically located immediately upstream of the root hair-morphogenetic genes. These observations suggest that auxin plays as an organizing node for environmental/hormonal pathways to modulate root hair growth. PMID:24273547

  18. Evaluation of DNA polymorphisms involving growth hormone relative to growth and carcass characteristics in Brahman steers.

    PubMed

    Beauchemin, V R; Thomas, M G; Franke, D E; Silver, G A

    2006-01-01

    Associations of DNA polymorphisms in growth hormone (GH) relative to growth and carcass characteristics in growing Brahman steers (N = 324 from 68 sires) were evaluated. Polymorphisms were an Msp-I RFLP and a leucine/valine SNP in the GH gene as well as a Hinf-I RFLP and a histidine/arginine SNP in transcriptional regulators of the GH gene, Pit-1 and Prop-1. Genotypic frequencies of the GH SNP, Pit-1 RFLP, and Prop-1 SNP were greater than 88% for one of the bi-allelic homozygous genotypes. Genotypic frequencies for the GH Msp-I RFLP genotypes were more evenly distributed with frequencies of 0.43, 0.42, and 0.15 for the genotypes of +/+, +/-, and -/-, respectively. Mixed model analyses of growth and carcass traits with genotype and contemporary group serving as fixed effects and sire fitted as a random effect suggested that sire was a significant source of variation (P < 0.05) in average daily gain, carcass yield, and marbling score. However, measures of growth and carcass traits were similar across GH Msp-I genotypes as steers were slaughtered when fat thickness was estimated to be approximately 1.0 cm. These polymorphisms within the GH gene and/or its transcriptional regulators do not appear to be informative predictors of growth and carcass characteristics in Brahman steers. This is partly due to the high level of homozygosity of genotypes. These findings do not eliminate the potential importance of these polymorphisms as predictors of growth and carcass traits in Bos taurus or Bos taurus x Bos indicus composite cattle. PMID:17117358

  19. Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

    NASA Technical Reports Server (NTRS)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1992-01-01

    Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

  20. Administration of Exogenous Growth Hormone Is Associated with Changes in Plasma and Intracellular Mammary Amino Acid Profiles and Abundance of the Mammary Gland Amino Acid Transporter SLC3A2 in Mid-Lactation Dairy Cows

    PubMed Central

    Sciascia, Quentin L.; Pacheco, David; McCoard, Susan A.

    2015-01-01

    The objectives of this study were to (1) identify changes in plasma and mammary intracellular amino acid (AA) profiles in dairy cows treated with growth hormone (GH), and (2) evaluate the expression of mammary gland genes involved in the transport of AA identified in (1). Eight non-pregnant (n = 4 per group) lactating dairy cows were treated with a single subcutaneous injection of either a slow-release formulation of commercially available GH (Lactotropin 500 mg) or physiological saline solution. Six days after treatment, cows were milked and blood collected from the jugular vein for the analysis of free AA in the plasma. Cows were euthanized and mammary tissue harvested. Treatment with GH increased milk, protein, fat and lactose yields, with no effect on dry matter intake. Plasma concentrations of lysine and group I AA decreased significantly, and arginine, methionine, tyrosine and arginine-family AA tended to decrease in GH-treated cows. Concentrations of intracellular glycine, serine and glutamate increased significantly, with a trend for decreased arginine observed in the mammary gland of GH-treated cows. A trend for increased concentrations of intracellular total AA, NEAA and arginine-family AA were observed in the mammary gland of GH-treated cows. Variance in the concentration of plasma methionine, tyrosine, valine, alanine, ornithine, BCAA, EAA was significantly different between treatments. Variance in the concentration of intracellular lysine, valine, glutamine, EAA and group II was significantly different between treatments. AA changes were associated with increased mRNA abundance of the mammary gland AA transporter SLC3A2. We propose that these changes occur to support increased milk protein and fatty acid production in the mammary gland of GH-treated cows via potential mTOR pathway signaling. PMID:26226162

  1. Gravity-induced asymmetric distribution of a plant growth hormone

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.; Momonoki, Y.

    1984-01-01

    Dolk (1936) demonstrated that gravistimulation induced an asymmetric distribution of auxin in a horizontally-placed shoot. An attempt is made to determine where and how that asymmetry arises, and to demonstrate that the endogenous auxin, indole-3-acetic acid, becomes asymmetrically distributed in the cortical cells of the Zea mays mesocotyl during 3 min of geostimulation. Further, indole-3-acetic acid derived by hydrolysis of an applied transport form of the hormone, indole-3-acetyl-myo-inositol, becomes asymmetrically distributed within 15 min of geostimulus time. From these and prior data is developed a working theory that the gravitational stimulus induces a selective leakage, or secretion, of the hormone from the vascular tissue to the cortical cells of the mesocotyl.

  2. Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma

    PubMed Central

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Salcido, Alyssa; Boopalan, Thiyagarajan; Arumugam, Arunkumar; Nandy, Sushmita; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signal-regulated kinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling, as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-β and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis. PMID:25301264

  3. 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.

  4. Plant growth hormones suppress the development of Harpophora maydis, the cause of late wilt in maize.

    PubMed

    Degani, Ofir; Drori, Ran; Goldblat, Yuval

    2015-01-01

    Late wilt, a severe vascular disease of maize caused by the fungus Harpophora maydis, is characterized by rapid wilting of maize plants before tasseling and until shortly before maturity. The pathogen is currently controlled by resistant maize cultivars, but the disease is constantly spreading to new areas. The plant's late phenological stage at which the disease appears suggests that plant hormones may be involved in the pathogenesis. This work revealed that plant growth hormones, auxin (Indole-3-acetic acid) and cytokinin (kinetin), suppress H. maydis in culture media and in a detached root assay. Kinetin, and even more auxin, caused significant suppression of fungus spore germination. Gibberellic acid did not alter colony growth rate but had a signal suppressive effect on the pathogens' spore germination. In comparison, ethylene and jasmonic acid, plant senescing and defense response regulators, had minor effects on colony growth and spore germination rate. Their associate hormone, salicylic acid, had a moderate suppressive effect on spore germination and colony growth rate, and a strong influence when combined with auxin. Despite the anti-fungal auxin success in vitro, field experiments with dimethylamine salt of  2,4-dichlorophenoxyacetic acid (that mimics the influence of auxin) failed to suppress the late wilt. The lines of evidence presented here reveal the suppressive influence of the three growth hormones studied on fungal development and are important to encourage further and more in-depth examinations of this intriguing hormonal complex regulatory and its role in the maize-H. maydis interactions. PMID:25649030

  5. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

    PubMed

    Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura

    2015-11-01

    RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed. PMID:26227443

  6. Inhibition by somatostatin (growth-hormone release-inhibiting hormone, GH-RIH) of gastric acid and pepsin and G-cell release of gastrin.

    PubMed Central

    Barros D'sa, A A; Bloom, S R; Baron, J H

    1978-01-01

    Somatostatin (cyclic growth-hormone release-inhibiting hormone--GH-RIH) was infused into dogs with gastric fistulae. Somatostatin inhibited gastric acid response to four gastric stimulants--insulin, food, histamine, and pentagastrin. Histamine- and pentagastrin-stimulated pepsins were inhibited similarly to inhibition of acid. Somatostatin inhibited the gastrin response to insulin and food. PMID:348581

  7. DNA sequences, recombinant DNA molecules and processes for producing bovine growth hormone-like polypeptides in high yield

    SciTech Connect

    Buell, G.N.

    1987-09-15

    This patent describes a process for increasing the yield of a bovine growth hormone-like polypeptide to at least 100 times that of a bovine growth hormone-like polypeptide encoded by a DNA sequence. The process comprises the steps of culturing a host transformed with a recombinant DNA molecule comprising DNA sequence encoding a Met ..lambda.. or ..lambda.. bovine growth hormone-like polypetide operatively linked to an expression control sequence. The ..lambda.. is an amino terminal deletion from the amino acid sequence of mature bovine growth hormone.

  8. Effects of growth hormone and insulin-like growth factor I on muscle in mouse models of human growth disorders.

    PubMed

    Clark, Ryan P; Schuenke, Mark; Keeton, Stephanie M; Staron, Robert S; Kopchick, John J

    2006-01-01

    The precise effects of growth hormone (GH) and insulin-like growth factor I (IGF-I) on muscle development and physiology are relatively unknown. Furthermore, there have been conflicting reports on the effects of GH/IGF-I on muscle. Distinguishing the direct effects of GH versus those of IGF-I is problematic, but animal models with altered GH/IGF-I action could help to alleviate some of the conflicting results and help to determine the independent actions of GH and IGF-I. The phenotypes of several mouse models, namely the GH receptor-gene-disrupted (GHR -/-) mouse and a variety of IGF-I -/- mice, are summarized, which ultimately will aid our understanding of this complex area. PMID:17259718

  9. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

    PubMed Central

    Argente, Jesús; Flores, Raquel; Gutiérrez-Arumí, Armand; Verma, Bhupendra; Martos-Moreno, Gabriel Á; Cuscó, Ivon; Oghabian, Ali; Chowen, Julie A; Frilander, Mikko J; Pérez-Jurado, Luis A

    2014-01-01

    The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences. Subject Categories Genetics, Gene Therapy ' Genetic Disease; Metabolism PMID:24480542

  10. Growth Control and Biophoton Radiation by Plant Hormones in Red Bean

    NASA Astrophysics Data System (ADS)

    Kai, Shoichi; Moriya, Tomoyuki; Fujimoto, Tokio

    1995-12-01

    The growth kinetics of seeds of red beans ( Phaseolus angularis ) was investigated by externally adding various hormones (gibberellin (GA3)), abscisic acid (ABA) and indole acetic acid (IAA)) during germination. For root growth of red beans, GA3 always acted as an activator while ABA as an inhibitor. IAA was both an activator and an inhibitor depending on its concentration. Root growth could be described by a stochastic logistic equation. The hormone concentration dependences of coefficients of the equation were determined. The hormone influences on biophoton radiation were also investgated. With GA3, the intensity of spontaneous bioluminescence increased with time and showed two strong radiation periods, in which strong localization of bioluminescence was induced. However with ABA and IAA, weaker bioluminescences were observed. The location of the strong radiation induced by GA3 was determined as the growing point near a root cap, by use of a two-dimensional photon counting system.

  11. [Fish growth-hormone genes: functionality evidence of paralogous genes in Levanidov's charr].

    PubMed

    Kamenskaya, D N; Pankova, M V; Atopkin, D M; Brykov, V A

    2015-01-01

    In the genome of most vertebrates growth-hormone gene is presented in a single copy, while in salmonids after one of the duplication events many genes were multiplied, including growth hormone gene. In salmonids, the growth-hormone gene exists as two independently inherited functional paralogues, gh1 and gh2. In this study, we performed a comparative analysis of gh1 and gh2 growth-hormone genes and their adjacent sequences in Levanidov's charr Salvelinus levanidovi to determine their functionality and define the potential differences. We found that both genes have the same gene structure and are composed of six exons (I-VI) and five introns (A, B, C, D, E). However, the respective gene sequences differ in length. A comparison of exons showed that the size of each exon is identical in both paralogues. The overall length of genes differs due to the varying lengths of introns. Coding sequence of both genes contains an open reading frame for 210 amino acids. We identified regulatory elements in the promoter region of both genes: TATA box, A/T-rich regions that contain binding sites for pituitary-specific transcriptional activator Pit-1, and regions responsible for interaction with other transcriptional activators and initiators, in particular hormone receptors. The obtained data indicate that both genes are functional. PMID:26510594

  12. [Association analysis between SNPs of the growth hormone receptor gene and growth traits in arctic fox].

    PubMed

    DU, Zhi-Heng; Liu, Zong-Yue; Bai, Xiu-Juan

    2010-06-01

    Using single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing, single nucleotide polymorphisms (SNPs) of growth hormone receptor (GHR) gene were detected in an arctic fox population. Correlation analysis between GHR polymorphisms and growth traits were carried out using the appropriate model. Four SNPs, G3A in the 5'UTR, C99T in the first exon, T59C and G65A in the fifth exon were identified on the arctic fox GHR gene. The G3A and C99T polymorphisms of GHR were associated with female fox body weight (Pamp;0.05) and the T59C and G65A polymorphisms of GHR were associated with male fox body weight (Pamp;0.05) and the skin length of the female fox (Pamp;0.01). Therefore, marker assistant selection on body weight and skin length of arctic foxes using these SNPs can be applied to get big and high quality arctic foxes. PMID:20566464

  13. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers.

    PubMed

    Letsch, Markus; Schally, Andrew V; Busto, Rebeca; Bajo, Ana M; Varga, Jozsef L

    2003-02-01

    The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control, P < 0.01; and 75% vs. castrated control, P < 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control, P < 0.01; and 68% vs. castrated control, P < 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (P < 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers. PMID:12538852

  14. Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers

    PubMed Central

    Letsch, Markus; Schally, Andrew V.; Busto, Rebeca; Bajo, Ana M.; Varga, Jozsef L.

    2003-01-01

    The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control, P < 0.01; and 75% vs. castrated control, P < 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control, P < 0.01; and 68% vs. castrated control, P < 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (P < 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers. PMID:12538852

  15. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

    PubMed Central

    Vetter, U; Zapf, J; Heit, W; Helbing, G; Heinze, E; Froesch, E R; Teller, W M

    1986-01-01

    Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life. Images PMID:3519682

  16. Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight

    NASA Technical Reports Server (NTRS)

    Jiang, Bian; Roy, Roland R.; Navarro, Christine; Edgerton, V. R.

    1993-01-01

    The effect of a 4-day-long spaceflight on the size and the enzyme properties of soleus fibers of rats and the effects of exogenous growth hormone (GH) on the atrophic response of the soleus muscle were investigated in four groups of rats: (1) control, (2) control plus GH treatment, (3) flight, and (4) flight plus GH treatment. Results showed that the fiber size and the type of myosin heavy chain expressed fibers (but not the metabolic properties) of the soleus were affected by four days of weightlessness and that the effects were not ameliorated by the administration of growth hormone.

  17. Growth hormone used to control intractable bleeding caused by radiation-induced gastritis

    PubMed Central

    Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

    2015-01-01

    Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis. PMID:26309374

  18. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B.

    1987-07-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse.

  19. Derivation of a growth hormone gene cassette for goat by mutagenesis of the corresponding bovine construct and its expression in Pichia pastoris.

    PubMed

    Reyes-Ruíz, Jorge M; Ascacio-Martínez, Jorge A; Barrera-Saldaña, Hugo A

    2006-07-01

    Recombinant bovine growth hormone (rbGH), a 191-aa polypeptide that affects animal growth and lactation, has been used for several years to increase milk production in dairy cattle. It has also been used in goats (Capra hircus) instead of their own hormone (chGH), which is still not available in the market. Since both hormones differ in only one amino acid residue, a strategy based on PCR mediated site-directed mutagenesis, was used to convert the bGH expression cassette harbored by an integration plasmid for Pichia pastoris into a chGH. Transformation by homologous recombination of Pichia pastoris GS115 strain with the linearized new plasmid resulted in transformants that, upon fermentation and induction with methanol, secreted a band with the expected size and immunoreactivity for GH. Production of total proteins secreted into culture medium (50 ml) was 20 microg/ml, of which 60% was chGH as judged by densitometry in SDS-PAGE. Its biological activity was confirmed in vitro when 3T3 pre-adipocytes exposed to the induced culture medium differentiated into adipocytes in cell culture. PMID:16799765

  20. Host stress hormone norepinephrine stimulates pneumococcal growth, biofilm formation and virulence gene expression

    PubMed Central

    2014-01-01

    Background Host signals are being shown to have a major impact on the bacterial phenotype. One of them is the endogenously produced catecholamine stress hormones, which are also used therapeutically as inotropes. Recent work form our laboratories have found that stress hormones can markedly increase bacterial growth and virulence. This report reveals that Streptococcus pneumoniae, a commensal that can also be a major cause of community acquired and nosocomial pneumonia, is highly inotrope responsive. Therapeutic levels of the stress hormone norepinephrine increased pneumococcal growth via a mechanism involving provision of iron from serum-transferrin and inotrope uptake, as well as enhancing expression of key genes in central metabolism and virulence. Collectively, our data suggests that Streptococcus pneumoniae recognises host stress as an environmental cue to initiate growth and pathogenic processes. Results Effects of a clinically attainable concentration of norepinephrine on S. pneumoniae pathogenicity were explored using in vitro growth and virulence assays, and RT-PCR gene expression profiling of genes involved in metabolism and virulence. We found that norepinephrine was a potent stimulator of growth, via a mechanism involving norepinephrine-delivery of transferrin-iron and internalisation of the inotrope. Stress hormone exposure also markedly increased biofilm formation. Importantly, gene profiling showed that norepinephrine significantly enhanced expression of genes involved in central metabolism and host colonisation. Analysis of the response of the pneumococcal pspA and pspC mutants to the stress hormone showed them to have a central involvement in the catecholamine response mechanism. Conclusions Collectively, our evidence suggests that the pneumococcus has mechanisms to recognise and process host stress hormones to augment its virulence properties. The ability to respond to host stress signals may be important for the pneumococcal transition from

  1. Gastrointestinal growth factors and hormones have divergent effects on Akt activation

    PubMed Central

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Thill, Michelle; Pace, Andrea; Hoffmann, K. Martin; Gonzalez-Fernandez, Lauro; Jensen, Robert T.

    2009-01-01

    Akt is a central regulator of apoptosis, cell growth and survival. Growth factors and some G-protein-coupled receptors (GPCR) regulate Akt. Whereas growth-factor activation of Akt has been extensively studied, the regulation of Akt by GPCR's, especially gastrointestinal hormones/neurotransmitters, remains unclear. To address this area, in this study the effects of GI growth factors and hormones/neurotransmitters were investigate in rat pancreatic acinar cells which are high responsive to these agents. Pancreatic acini expressed Akt and 5 of 7 known pancreatic growth-factors stimulate Akt phosphorylation (T308, S473) and translocation. These effects are mediated by p85 phosphorylation and activation of PI3K. GI hormones increasing intracellular cAMP had similar effects. However, GI-hormones/neurotransmitters[CCK, bombesin,carbachol] activating phospholipase C (PLC) inhibited basal and growth-factor-stimulated Akt activation. Detailed studies with CCK, which has both physiological and pathophysiological effects on pancreatic acinar cells at different concentrations, demonstrated CCK has a biphasic effect: at low concentrations(pM) stimulating Akt by a Src-dependent mechanism and at higher concentrations(nM) inhibited basal and stimulated Akt translocation, phosphorylation and activation, by de-phosphorylating p85 resulting in decreasing PI3K activity. This effect required activation of both limbs of the PLC-pathway and a protein tyrosine phosphatase, but was not mediated by p44/42 MAPK, Src or activation of a serine phosphatase. Akt inhibition by CCK was also found in vivo and in Panc-1 cancer cells where it inhibited serum-mediated rescue from apoptosis. These results demonstrate that GI growth factors as well as gastrointestinal hormones/neurotransmitters with different cellular basis of action can all regulate Akt phosphorylation in pancreatic acinar cells. This regulation is complex with phospholipase C agents such as CCK, because both stimulatory and inhibitory

  2. Effects of oral chlortetracycline and dietary protein level on plasma concentrations of growth hormone and thyroid hormones in beef steers before and after challenge with a combination of thyrotropin-releasing hormone and growth hormone-releasing hormone.

    PubMed

    Rumsey, T S; McLeod, K; Elsasser, T H; Kahl, S; Baldwin, R L

    1999-08-01

    The objective of this study was to determine the effect of a subtherapeutic level of chlortetracycline (CTC) fed to growing beef steers under conditions of limited and adequate dietary protein on plasma concentrations of GH, thyroid-stimulating hormone (TSH), and thyroid hormones before and after an injection of thyrotropin-releasing hormone (TRH) + GHRH. Young beef steers (n = 32; average BW = 285 kg) were assigned to a 2x2 factorial arrangement of treatments of either a 10 or 13% crude protein diet (70% concentrate, 15% wheat straw, and 15% cottonseed hulls) and either a corn meal carrier or carrier + 350 mg of CTC daily top dressed on the diet. Steers were fed ad libitum amounts of diet for 56 d, and a jugular catheter was then placed in each steer in four groups (two steers from each treatment combination per group) during four consecutive days (one group per day). Each steer was injected via the jugular catheter with 1.0 microg/kg BW TRH + .1 microg/kg BW GHRH in 10 mL of saline at 0800. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 120, 240, and 360 min after releasing hormone injection. Plasma samples were analyzed for GH, TSH, thyroxine (T4), and triiodothyronine (T3). After 84 d on trial, the steers were slaughtered and the pituitary and samples of liver were collected and analyzed for 5'-deiodinase activity. Feeding CTC attenuated the GH response to releasing hormone challenge by 26% for both area under the response curve (P<.03) and peak response (P<.10). Likewise, CTC attenuated the TSH response to releasing hormone challenge for area under the response curve by 16% (P<.10) and peak response by 33% (P<.02), and attenuated the T4 response for area under the curve by 12% (P<.08) and peak response by 14% (P<.04). Type II deiodinase activity in the pituitary was 36% less (P<.02) in CTC-fed steers than in steers not fed CTC. The results of this study are interpreted to suggest that feeding subtherapeutic levels of CTC to young

  3. 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.

  4. Microstructural dependence of aqueous-environment-assisted crack growth and hydrogen uptake in AA 7050

    NASA Astrophysics Data System (ADS)

    Young, Lisa Marie

    This goal of this research was to explain the effects of heat treatment, Cu content, and electrode potential (EApp) on short-transverse aqueous environment assisted cracking (EAC) in a precipitation hardened Al-Zn-Mg-(Cu) alloy. Substantial intergranular EAC susceptibility was observed in several underaged (UA) and peak aged (PA) tempers of AA 7050, where increasing E App produced a slow crack growth rate (da/dt) incubation and transition to fast da/dt. Above the transition potential, da/dt was dramatically increased by further increases in EApp. In contrast the overaged (OA) condition was highly EAC resistant, exhibiting transgranular da/dt ≤2 x 10-8 mm/sec or ≈ 10,000 times slower than PA. Crack growth rates in the low Cu alloy were several orders of magnitude higher than those exhibited by the high Cu material at similar EApp and were only slightly reduced on overaging. Thermal desorption spectroscopy (TDS) results showed enhanced hydrogen uptake in fast-cracking EAC regions compared to as-received hydrogen concentrations. Hydrogen analyses were complicated by the dependence of H-production and uptake on wake exposure time and a pH gradient in the occluded crack environment. Trends between applied anodic potential, crack wake H concentration (normalized by the wake exposure time), and aqueous da/dt were observed. Nuclear reaction analysis revealed unexpectedly high near-surface H concentrations ( ≈ 2000 wppm). The H-concentration profiles indicate that the observed da/dt can be rate-limited by bulk H-diffusion into the crack tip process zone, where EAC is promoted by a hydrogen embrittlement mechanism. The transition potential to fast da/dt increased in the anodic direction with increased isothermal aging time. Additionally, the presence of large Cu-containing second phase particles (S-phase) on high angle grain boundaries partially negated the beneficial effect of overaging on EAC in the Cu-containing alloy, an effect not observed in humid air cracking

  5. Effect of growth hormone and resistance exercise on muscle growth in young men.

    PubMed

    Yarasheski, K E; Campbell, J A; Smith, K; Rennie, M J; Holloszy, J O; Bier, D M

    1992-03-01

    The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function. PMID:1550219

  6. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

    PubMed

    Lang, C H; Pollard, V; Fan, J; Traber, L D; Traber, D L; Frost, R A; Gelato, M C; Prough, D S

    1997-07-01

    The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection. PMID:9249574

  7. COMPLEMENTARY DNA CLONING AND EXPRESSION STUDIES FOR PROLACTIN, GROWTH HORMONE, SOMATOLACTIN AND IGF-I IN YELLOW PERCH PERCA FLAVESCENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In several species of teleost, the pituitary hormones prolactin (PRL), growth hormone (GH) and somatolactin (SL) show different secretory patterns based on gender and development and can also be influenced by abiotic factors (e.g., salinity, photoperiod & temperature). Plasma insulin-like growth fa...

  8. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glyc...

  9. Growth Hormone Effects in Immune Stress: AKT/eNOS Signaling Module in the Cellular Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The activation of the constitutive endothelial nitric-oxide synthase (eNOS) and expression of inducible NOS (iNOS) with subsequent nitric oxide production are among the early cellular responses that follow in a systemic exposure of animals to lipopolysaccharide (LPS). Growth hormone (GH) has been sh...

  10. Increased daylength stimulates plasma growth hormone and gill Na+, K+ and -ATPase Atlantic salmon (Salmo salar )

    USGS Publications Warehouse

    McCormick, S.D.; Bjornsson, Bjorn Thrandur; Sheridan, M.; Eilertson, C.; Carey, J.B.; O'Dea, M.

    1995-01-01

    Atlantic salmon juveniles reared at constant temperature (9–10°C) were exposed to four photoperiod treatment and sampled every 2 weeks from January through May. Fish reared under normal photoperiod exhibited eight-and three fold increases in plasma growth hormone and gill Na+, K+-ATPase activity, respectively, between January and April. Fish exposed to abrupt increases in daylength (LD 15:9) in February or March responded with earlier increases in plasma growth hormone and gill Na+, K+-ATPase activity, and earlier decreases in condition factor relative to fish in the normal photoperiod group. Fish maintained under short daylength (LD 9:15) from January to May exhibited delayed and muted increases in plasma growth hormone and gill Na+, K+-ATPase activity. Plasma thyroxine exhibited a 2.5-fold increase from February to late March in the normal photoperiod group, was generally lower in the LD 9:15 group, but exhibited no obvious response to abrupt increases in daylength. There was an increase in plasma 3,5,3′-triiodo-l-thyronine with time in all groups (43–80%) but no significant response to photoperiod. Plasma levels of somatostatin-25 were highest in the LD 9:15 group, but there was no detectable response to increased daylength in any of the photoperiod treatments. The results indicate that plasma growth hormone is responsive to increased daylength and may be causally related to subsequent increases in gill Na+, K+-ATPase.

  11. Hormone replacement therapy in children: The use of growth hormone and IGF-I.

    PubMed

    Pfäffle, Roland

    2015-06-01

    Recombinant human GH (rhGH) has been available since 1985. This article gives an overview, what has been achieved over the past 30 years in respect to optimization of rhGH treatment for the individual child with GH deficiency and what are the safety issues concerned with this treatment. In the last twenty years significant scientific progress has been made in the diagnosis of GH deficiency, the genetic disorders that are associated with pituitary GH deficiency and the genetics that influence growth in general. On the other hand rhGH is not only used in states of GH deficiency but also various conditions without a proven GH deficiency by classical standards. Clinical studies that investigated both the genetics of growth and the individual responses to rhGH therapy in these patient populations were able to refine our concept about the physiology of normal growth. In most patients under rhGH treatment there is a considerable short-term effect, however the overall gain in growth obtained by a long-term treatment until final height still remains a matter of debate in some of the conditions treated. Also first studies on the long-term safety risks of rhGH treatment have raised the question whether this treatment is similarly safe for all the patient groups eligible for such a treatment. Therefore even in the face of a longstanding safety record of this drug replacement therapy the discussion about the right cost and risk to benefit ratio is continuing. Consequently there is still a need for carefully conducted long-term studies that use modern anthropometric, genetic, and laboratory techniques in order to provide the necessary information for clinicians to select the patients that will benefit best from this valuable treatment without any long term risk. PMID:26051295

  12. Effects of sericin on the testicular growth hormone/insulin-like growth factor-1 axis in a rat model of type 2 diabetes

    PubMed Central

    Song, Cheng-Jun; Yang, Zhen-Jun; Tang, Qi-Feng; Chen, Zhi-Hong

    2015-01-01

    This study investigated the effects of sericin on the testicular growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in rats with type 2 diabetes mellitus. Forty rats were randomly assigned to normal control, type 2 diabetes mellitus, sericin and metformin treated groups. Type 2 diabetes was established by repeated intraperitoneal injection of streptozotocin, and identified by blood glucose ≥16.7 mmol/L at 1 week. The diabetic rats were given no other treatment, these rats in the sericin group were intragastrically perfused with 2.4 g/kg sericin and the metformin treated rats were intragastrically perfused with 55.33 mg/kg Metformin daily for 35 consecutive days. Enzyme-linked immunosorbent assays were used to determine serum testosterone, growth hormone and IGF-1 levels. Immunohistochemical staining, western blotting and reverse transcription-PCR were used to determine testicular growth hormone, growth hormone receptor and IGF-1 expression. The sericin significantly reduced serum growth hormone levels, downregulated growth hormone expression, increased serum testosterone and IGF-1 levels, and upregulated testicular growth hormone receptor and IGF-1 expression. Moreover, there were no significant differences in any of the parameters between the sericin and metformin treated groups. These findings indicated that sericin improved spermatogenic function through regulating the growth hormone/IGF-1 axis, thereby protecting reproductive function against diabetes-induced damage. PMID:26379831

  13. Effects of sericin on the testicular growth hormone/insulin-like growth factor-1 axis in a rat model of type 2 diabetes.

    PubMed

    Song, Cheng-Jun; Yang, Zhen-Jun; Tang, Qi-Feng; Chen, Zhi-Hong

    2015-01-01

    This study investigated the effects of sericin on the testicular growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in rats with type 2 diabetes mellitus. Forty rats were randomly assigned to normal control, type 2 diabetes mellitus, sericin and metformin treated groups. Type 2 diabetes was established by repeated intraperitoneal injection of streptozotocin, and identified by blood glucose ≥16.7 mmol/L at 1 week. The diabetic rats were given no other treatment, these rats in the sericin group were intragastrically perfused with 2.4 g/kg sericin and the metformin treated rats were intragastrically perfused with 55.33 mg/kg Metformin daily for 35 consecutive days. Enzyme-linked immunosorbent assays were used to determine serum testosterone, growth hormone and IGF-1 levels. Immunohistochemical staining, western blotting and reverse transcription-PCR were used to determine testicular growth hormone, growth hormone receptor and IGF-1 expression. The sericin significantly reduced serum growth hormone levels, downregulated growth hormone expression, increased serum testosterone and IGF-1 levels, and upregulated testicular growth hormone receptor and IGF-1 expression. Moreover, there were no significant differences in any of the parameters between the sericin and metformin treated groups. These findings indicated that sericin improved spermatogenic function through regulating the growth hormone/IGF-1 axis, thereby protecting reproductive function against diabetes-induced damage. PMID:26379831

  14. Neural Growth Hormone Implicated in Body Weight Sex Differences

    PubMed Central

    Bonthuis, Paul J.

    2013-01-01

    As for many human diseases, the incidence of obesity and its associated health risks are sexually dimorphic: worldwide the rate of obesity is higher in women. Sex differences in metabolism, appetite, body composition, and fat deposition are contributing biological factors. Gonadal hormones regulate the development of many sexually dimorphic traits in humans and animals, and, in addition, studies in mice indicate a role for direct genetic effects of sex chromosome dosage on body weight, deposition of fat, and circadian timing of feeding behavior. Specifically, mice of either sex with 2 X chromosomes, typical of normal females, have heavier body weights, gain more weight, and eat more food during the light portion of the day than mice of either sex with a single X chromosome. Here we test the effects of X chromosome dosage on body weight and report that gonadal females with 2 X chromosomes express higher levels of GH gene (Gh) mRNA in the preoptic area (POA) of the hypothalamus than females with 1 X chromosome and males. Furthermore, Gh expression in the POA of the hypothalamus of mice with 2 X chromosomes correlated with body weight; GH is known to have orexigenic properties. Acute infusion of GH into the POA increased immediate food intake in normal (XY) males. We propose that X inactivation–escaping genes modulate Gh expression and food intake, and this is part of the mechanism by which individuals with 2 X chromosomes are heavier than individuals with a single X chromosome. PMID:23861378

  15. [Study on exogenous hormones inducing parthenocarpy fruit growth and development and quality of Siraitia grosvenorii].

    PubMed

    Huang, Jie; Tu, Dong-ping; Ma, Xiao-jun; Mo, Chang-ming; Pan, Li-mei; Bai, Long-hua; Feng, Shi-xin

    2015-09-01

    To explore the growth and development and analyze the quality of the parthenocarpy fruit induced by exogenous hormones of Siraitia grosvenorii. the horizontal and vertical diameter, volume of the fruit were respectively measured by morphological and the content of endogenous hormones were determined by ELISA. The size and seed and content of mogrosides of mature fruit were determined. The results showed that the fruit of parthenocarpy was seedless and its growth and development is similar to the diploid fruit by hand pollination and triploid fruit by hand pollination or hormones. But the absolute value of horizontal and vertical diameter, volume of parthenocarpy fruit was less than those of fruit by hand pollination, while triploid was opposite. The content of IAA, ABA and ratio of ABA/GA was obviously wavy. At 0-30 d the content of IAA and ABA of parthenocarpy fruit first reduced then increased, content of IAA and GA parthenocarpy fruit was higher than that of fruit by hand pollination. Mogrosides of parthenocarpy fruit was close to pollination fruit. Hormones can induce S. grosvenorii parthenocarpy to get seedless fruit and the fruit shape and size and quality is close to normal diploid fruit by hand pollination and better than triploid fruit by hormone or hand pollination. PMID:26983201

  16. Information for People Treated with Human Growth Hormone (Comprehensive Report)

    MedlinePlus

    ... org ) is a nonprofit organization concerned with children's growth disorders and adult GH deficiency. The HGF has information available online and through its toll-free number, 1–800–451–6434. The HGF also supports an Internet mailing list to help the exchange of information ...

  17. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

    PubMed

    Lang, Charles H; Frost, Robert A

    2002-05-01

    The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance. PMID:11953652

  18. Structural and Functional Divergence of Growth Hormone-Releasing Hormone Receptors in Early Sarcopterygians: Lungfish and Xenopus

    PubMed Central

    Tam, Janice K. V.; Chow, Billy K. C.; Lee, Leo T. O.

    2013-01-01

    The evolutionary trajectories of growth hormone-releasing hormone (GHRH) receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR) in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR2 in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP) receptor (PRPR). In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi) and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR2 in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR2 was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR2 had the highest expression in brain, and interestingly, X. laevis GHRHR2 also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR2, which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP. PMID:23308232

  19. New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor

    PubMed Central

    Schally, Andrew V.; Takeuchi, Lauro M.; Popovics, Petra; Jaszberenyi, Miklos; Vidaurre, Irving; Zarandi, Marta; Cai, Ren-Zhi; Block, Norman L.; Hare, Joshua M.; Rick, Ferenc G.

    2015-01-01

    Background We previously showed that growth hormone-releasing hormone (GHRH) agonists are cardioprotective following myocardial infarction (MI). Here, our aim was to evaluate the in vitro and in vivo activities of highly potent new GHRH agonists, and elucidate their mechanisms of action in promoting cardiac repair. Methods and Results H9c2 cells were cultured in serum-free medium, mimicking nutritional deprivation. GHRH agonists decreased calcium influx and significantly improved cell survival. Rats with cardiac infarction were treated with GHRH agonists or placebo for four weeks. MI size was reduced by selected GHRH agonists (JI-38, MR-356, MR-409); this accompanied an increased number of cardiac c-kit+ cells, cellular mitotic divisions, and vascular density. One week post-MI, MR-409 significantly reduced plasma levels of IL-2, IL-6, IL-10 and TNF-α compared to placebo. Gene expression studies revealed favorable outcomes of MR-409 treatment partially result from inhibitory activity on pro-apoptotic molecules and pro-fibrotic systems, and by elevation of bone morphogenetic proteins. Conclusions Treatment with GHRH agonists appears to reduce the inflammatory responses post-MI and may consequently improve mechanisms of healing and cardiac remod eling by regulating pathways involved in fibrosis, apoptosis and cardiac repair. Patients with cardiac dysfunction could benefit from treatment with novel GHRH agonists. PMID:25797248

  20. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    PubMed

    Tam, Janice K V; Chow, Billy K C; Lee, Leo T O

    2013-01-01

    The evolutionary trajectories of growth hormone-releasing hormone (GHRH) receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR) in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2) in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP) receptor (PRPR). In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi) and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2) in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2) was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2) had the highest expression in brain, and interestingly, X. laevis(GHRHR2) also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2), which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP. PMID:23308232

  1. Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

    PubMed Central

    Ludwig, Barbara; Rotem, Avi; Schmid, Janine; Weir, Gordon C.; Colton, Clark K.; Brendel, Mathias D.; Neufeld, Tova; Block, Norman L.; Yavriyants, Karina; Steffen, Anja; Ludwig, Stefan; Chavakis, Triantafyllos; Reichel, Andreas; Azarov, Dimitri; Zimermann, Baruch; Maimon, Shiri; Balyura, Mariya; Rozenshtein, Tania; Shabtay, Noa; Vardi, Pnina; Bloch, Konstantin; de Vos, Paul; Schally, Andrew V.; Bornstein, Stefan R.; Barkai, Uriel

    2012-01-01

    Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing β-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation. PMID:22393012

  2. Antagonists of growth hormone-releasing hormone (GH-RH) enhance tumour growth inhibition induced by androgen deprivation in human MDA-Pca-2b prostate cancers.

    PubMed

    Letsch, M; Schally, A V; Stangelberger, A; Groot, K; Varga, J L

    2004-02-01

    In the present study, we investigated whether the growth hormone-releasing hormone (GH-RH) antagonist JV-1-38 could enhance the effects of androgen deprivation produced by the anti-androgen Flutamide and luteinising hormone-releasing hormone (LH-RH) agonist Decapeptyl in an experimental model of human androgen-sensitive MDA PCa 2b prostate carcinoma implanted subcutaneously (s.c.) into nude mice. We also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) the effects of combined treatment on the mRNA expression for prostate-specific antigen (PSA) and measured serum PSA levels. In experiment 1, GH-RH antagonist JV-1-38 greatly inhibited tumour growth in combination with Decapeptyl, but was ineffective when given alone. Thus, combined therapy with JV-1-38 at 20 microg/day and Decapeptyl microcapsules releasing 12.5 microg/day for 29 days inhibited significantly (P<0.01) MDA PCa 2b tumour growth by 65%, compared with controls. Combined treatment also significantly (P<0.05) decreased serum PSA levels by 52% and reduced tumour weight by 54% vs. controls. In experiment 2, GH-RH antagonist JV-1-38 at 20 microg/day likewise showed powerful growth inhibitory effects when combined with Flutamide (25 mg/kg/day) for 21 days. Combined treatment with JV-1-38 and slow-release pellets of Flutamide significantly (P<0.001) inhibited tumour growth by 61% versus controls, and was significantly (P<0.05) more effective than Flutamide or JV-1-38 alone. Combination therapy also reduced significantly (P<0.001) tumour weight and serum PSA levels by 59 and 47%, respectively. The mRNA expression for PSA in MDA PCa 2b tumours was not changed by JV-1-38, Decapeptyl and Flutamide alone or in their respective combinations. Our findings suggest that GH-RH antagonists could enhance the tumour inhibitory effects of androgen deprivation for the primary therapy of patients with advanced prostate carcinoma. PMID:14746863

  3. Turnover of growth hormone receptors in rat adipocytes

    SciTech Connect

    Gorin, E.; Goodman, H.M.

    1985-05-01

    Adipocytes isolated from the epididymal fat pads of normal rats specifically bound (/sup 125/I)human GH (( /sup 125/I)hGH). Preincubation of cells with 20 micrograms/ml cycloheximide, an inhibitor of protein synthesis, produced a progressive loss of ability to bind (/sup 125/I)hGH specifically. Loss of binding sites with time followed first order kinetics and had a half-time of about 45 min regardless of whether GH was present or absent during treatment with cycloheximide. Nonspecific binding of labeled hormone was unchanged by cycloheximide. Similar results were obtained when adipocytes were incubated with 200 micrograms/ml puromycin, another inhibitor of translation, but incubation with 5 micrograms/ml actinomycin D, an inhibitor of transcription, for 2.5 h had no effect on the binding of (/sup 125/I)hGH by adipocytes. The findings are not attributable to cell death, since oxidation of (U-/sup 14/C) glucose to /sup 14/CO/sub 2/ and binding of (/sup 125/I)insulin were unaffected in replicate cell populations exposed to the same treatments. Diminished binding could not be attributed to an effect of cycloheximide to hasten the degradation of receptor-bound hGH. Treatment of adipocytes with 0.1 mg/ml trypsin for 10 min virtually abolished their ability to bind (/sup 125/I)hGH specifically, but binding capability gradually returned after removal of trypsin and was nearly restored to pretrypsin levels by 2 h. Addition of cycloheximide to the incubation medium after removal of trypsin completely prevented recovery of binding capability.

  4. Recombinant growth hormone therapy for cystic fibrosis in children and young adults

    PubMed Central

    Thaker, Vidhu; Haagensen, Alexandra L; Carter, Ben; Fedorowicz, Zbys; Houston, Brian W

    2015-01-01

    Background Cystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention. Objectives To evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 11 February 2015. We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 04 March 2015. Selection criteria Randomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing). Data collection and analysis Two authors independently screened papers, extracted trial details and assessed their risk of bias. Main results Four controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. One study showed moderate improvement at one time point

  5. Growth hormone, luteinizing hormone, and follicle-stimulating hormone regulation by neuropeptide Y in both sexes of the cichlid fish, Cichlasoma dimerus.

    PubMed

    Di Yorio, M P; Delgadin, T H; Pérez Sirkin, D I; Vissio, P G

    2015-08-01

    Neuropeptide Y (NPY) is considered the most potent orexigenic peptide, increasing before meal time and during fasting. In teleost, most studies on NPY action upon growth hormone (GH) and luteinizing hormone (LH) were conducted in females or group of animals without sex discrimination. The aim of this study was to evaluate whether NPY modulates the expression and release of GH and gonadotropins in both sexes of Cichlasoma dimerus. By double-label immunofluorescence, we first determined the association between NPY fibers and pituitary cells. In addition, we performed in vitro studies to evaluate the effect of NPY on GH and gonadotropins expression by real-time PCR, and release by Western blot, in males and females separately. Contacts between NPY fibers and GH and follicle-stimulating hormone (FSH)-producing cells were detected, indicating possible functional relationships. We observed an increase in GH release in the culture medium at 2 nM for males (p = 0.043) and 20 nM for females (p = 0.028). Pituitary FSH release was stimulated at 20 nM (p = 0.026) and 200 nM (p = 0.033) for males and females, respectively. Finally, NPY only increased β-LH mRNA expression at 20 nM in females (p = 0.028) and its release at 2 nM (p = 0.049) and 200 nM for males (p = 0.005) and 200 nM for females (p = 0.018). In conclusion, NPY acts as a GH-, LH- and FSH-releasing factor, in a dose- and sex-dependent way. PMID:25869217

  6. MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

    PubMed

    Jiang, H; Ge, X

    2014-01-01

    Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals. PMID:24166991

  7. Growth hormone therapy in children with CKD after more than two decades of practice.

    PubMed

    Rees, Lesley

    2016-09-01

    This review focuses on the evidence for the efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with all stages of chronic kidney disease (CKD) and at all ages. It describes the improving height prognosis for our patients both with and without rhGH; explains the underlying hormonal abnormalities that provide the rationale for rhGH use in CKD and the endocrine changes that accompany treatment; and views on who warrants treatment, with what dose, and how long for. PMID:26369925

  8. Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel

    PubMed Central

    Buchholz, Stefan; Schally, Andrew V.; Engel, Jörg B.; Hohla, Florian; Heinrich, Elmar; Koester, Frank; Varga, Jozsef L.; Halmos, Gabor

    2007-01-01

    Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various cancers. In this study, we investigated the effectiveness of treatment with GHRH antagonist JMR-132 alone and in combination with docetaxel chemotherapy in nude mice bearing MX-1 human breast cancers. Specific high-affinity binding sites for GHRH were found on MX-1 tumor membranes using ligand competition assays with 125I-labeled GHRH antagonist JV-1-42. JMR-132 displaced radiolabeled JV-1-42 with an IC50 of 0.14 nM, indicating a high affinity of JMR-132 to GHRH receptors. Treatment of nude mice bearing xenografts of MX-1 with JMR-132 at 10 μg per day s.c. for 22 days significantly (P < 0.05) inhibited tumor volume by 62.9% and tumor weight by 47.8%. Docetaxel given twice at a dose of 20 mg/kg i.p. significantly reduced tumor volume and weight by 74.1% and 58.6%, respectively. Combination treatment with JMR-132 (10 μg/day) and docetaxel (20 mg/kg i.p.) led to growth arrest of most tumors as shown by an inhibition of tumor volume and weight by 97.7% and 95.6%, respectively (P < 0.001). Because no vital cancer cells were detected in some of the excised tumors, a total regression of the tumors was achieved in some cases. Treatment with JMR-132 also strongly reduced the concentration of EGF receptors in MX-1 tumors. Our results demonstrate that GHRH antagonists might provide a therapy for breast cancer and could be combined with docetaxel chemotherapy to enhance the efficacy of treatment. PMID:17261802

  9. Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

    NASA Technical Reports Server (NTRS)

    Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

    1997-01-01

    Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone

  10. Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome.

    PubMed

    Vurallı, Doğuş; Gönç, Nazlı; Vidaud, Dominique; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

    2016-03-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD. PMID:26758488

  11. Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome

    PubMed Central

    Vurallı, Doğuş; Gönç, Nazlı; Vidaud, Dominique; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

    2016-01-01

    Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD. PMID:26758488

  12. Adipocytokines, gut hormones and growth factors in anorexia nervosa.

    PubMed

    Kowalska, Irina; Karczewska-Kupczewska, Monika; Strączkowski, Marek

    2011-09-18

    Anorexia nervosa is a complex eating disorder of unknown etiology which affects adolescent girls and young women and leads to chronic malnutrition. Clinical manifestations of prolonged semistarvation include a variety of physical features and psychiatric disorders. The study of different biological factors involved in the pathophysiology of anorexia nervosa is an area of active interest. In this review we have described the role of adipocytokines, neurotrophins, peptides of the gastrointestinal system and growth factors in appetite regulation, energy balance and insulin sensitivity in anorexia nervosa patients. PMID:21699889

  13. Pros of priming in the diagnosis of growth hormone deficiency.

    PubMed

    Gonc, E Nazli; Ozon, Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

    2011-01-01

    Priming with sex steroids in stimulation tests for the diagnosis of GHD is still under debate. Most of the data on utility of priming during GH stimulation so far seem to support its use in the diagnosis of GHD in childhood. There is a propensity to treat growth retarded children who test subnormally to stimulation tests with GH. However, some studies analyzing the final height or height gain during GH treatment in such children failed to show any improvement in height. This paper summarizes previous studies on priming to analyze the utility of priming as a valid method to better the diagnostic capacity of the test. PMID:21528807

  14. Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

    PubMed

    Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

    2016-07-01

    To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs. PMID:26631054

  15. Burden of Growth Hormone Deficiency and Excess in Children.

    PubMed

    Fideleff, Hugo L; Boquete, Hugo R; Suárez, Martha G; Azaretzky, Miriam

    2016-01-01

    Longitudinal growth results from multifactorial and complex processes that take place in the context of different genetic traits and environmental influences. Thus, in view of the difficulties in comprehension of the physiological mechanisms involved in the achievement of normal height, our ability to make a definitive diagnosis of GH impairment still remains limited. There is a myriad of controversial aspects in relation to GH deficiency, mainly related to diagnostic controversies and advances in molecular biology. This might explain the diversity in therapeutic responses and may also serve as a rationale for new "nonclassical" treatment indications for GH. It is necessary to acquire more effective tools to reach an adequate evaluation, particularly while considering the long-term implications of a correct diagnosis, the cost, and safety of treatments. On the other hand, overgrowth constitutes a heterogeneous group of different pathophysiological situations including excessive somatic and visceral growth. There are overlaps in clinical and molecular features among overgrowth syndromes, which constitute the real burden for an accurate diagnosis. In conclusion, both GH deficiency and overgrowth are a great dilemma, still not completely solved. In this chapter, we review the most burdensome aspects related to short stature, GH deficiency, and excess in children, avoiding any details about well-known issues that have been extensively discussed in the literature. PMID:26940390

  16. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. .

    PubMed

    Wüster, C; Abs, R; Bengtsson, B A; Bennmarker, H; Feldt-Rasmussen, U; Hernberg-Ståhl, E; Monson, J P; Westberg, B; Wilton, P

    2001-02-01

    To assess the influence of factors affecting fracture risk and bone density in adult hypopituitary patients with growth hormone deficiency (GHD), data from a large-scale pharmacoepidemiological survey (the Pharmacia & Upjohn International Metabolic Database [KIMS]) were analyzed and compared with data from a control population (the European Vertebral Osteoporosis Study [EVOS]). The KIMS group consisted of 2084 patients (1112 men and 972 women) with various types of pituitary disease and EVOS consisted of 1176 individuals (581 men and 595 women). Fracture and bone mineral density (BMD) data were available from 2024 patients from the KIMS group and 392 patients from EVOS. The prevalence of fractures in patients with hypopituitarism was 2.66 times that in the non-GH-deficient EVOS population. Adult-onset hypopituitarism with GHD was associated with a higher fracture risk than childhood-onset disease, and patients with isolated GHD had a similar prevalence of fractures to those with multiple pituitary hormone deficiencies. Hormonal replacement therapy with L-thyroxine, glucocorticoids, and sex steroids did not affect the risk of fracture in KIMS patients. In addition, fracture rates in KIMS were independent of body mass index (BMI) and the country of origin. However, smoking was associated with a higher fracture rate in this group. In summary, this is the first large-scale analysis to support the hypothesis of an increased fracture risk in adult patients with hypopituitarism and GHD. This increased risk appears to be attributable to GHD alone, rather than to other pituitary hormone deficiencies or to their replacement therapy. PMID:11204440

  17. Short Stature in Chronic Kidney Disease Treated with Growth Hormone and an Aromatase Inhibitor

    PubMed Central

    Mendley, Susan R.; Spyropoulos, Fotios; Counts, Debra R.

    2015-01-01

    We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty. PMID:26101681

  18. Primate mammary development. Effects of hypophysectomy, prolactin inhibition, and growth hormone administration.

    PubMed Central

    Kleinberg, D L; Niemann, W; Flamm, E; Cooper, P; Babitsky, G; Valensi, Q

    1985-01-01

    The pituitary gland has been found to be an important factor in mammary development in primates. Hypophysectomy in 12 sexually immature monkeys caused significant inhibition of estradiol (E2)-induced mammary growth and development. A histological index of mammary development in sexually immature hypophysectomized animals was lower (0.82) than in intact E2-treated controls (3.4; P less than 0.008). Hypophysectomy also inhibited growth of the mammary gland as judged by a size index. Despite the hypophysectomy, E2 stimulated some, albeit blunted, mammary growth and development, which may have been due to incomplete hypophysectomy. Selective inhibition of prolactin by ergot drugs in intact animals did not prevent full mammary development, suggesting that there may be pituitary mammogens other than prolactin, or that very low or unmeasurable concentrations of prolactin were sufficient to synergize with E2 to cause full acinar development. The mean histological index was 3.08 in E2-treated animals and 3.16 in animals treated with E2 plus pergolide. There was also no difference in the size of the glands. We evaluated the effect of growth hormone on mammary development by treating three hypophysectomized animals with pure 22,000 mol wt human growth hormone (hGH) (Genentech, Inc., South San Francisco, CA). We found that physiological or slightly supraphysiological concentrations of hGH in animals with unmeasurable prolactin were incapable of restoring the capacity of E2 to induce full mammary growth. These findings suggest that, if growth hormone is a mammary mitogen, that physiological concentrations are insufficient to synergize with E2 to induce full mammary growth or that other forms of hGH are mammogenic. Our studies suggest that the role of the pituitary gland in mammary mitogenesis in primates is more complicated than previously thought. They also raise the possibility that heretofore unidentified pituitary substances may be mammogenic. Images PMID:4008646

  19. A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results.

    PubMed

    Saccà, Francesco; Quarantelli, Mario; Rinaldi, Carlo; Tucci, Tecla; Piro, Raffaele; Perrotta, Gaetano; Carotenuto, Barbara; Marsili, Angela; Palma, Vincenzo; De Michele, Giuseppe; Brunetti, Arturo; Brescia Morra, Vincenzo; Filla, Alessandro; Salvatore, Marco

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease with motor neuron degeneration. Riluzole is the only available treatment. Two-thirds of ALS patients present with growth hormone (GH) deficiency. The aim of this study is to determine if add-on of GH to riluzole, with an individually regulated dose based on Insulin-like growth factor 1 (IGF-I) production, was able to reduce neuronal loss in the motor cortex, reduce mortality, and improve motor function of ALS patients. Patients with definite/probable ALS, in treatment with riluzole, aged 40-85 years, and with disease duration ≤3 years were enrolled. The study was randomized, placebo controlled, and double blind. Before treatment, patients were tested with a GH releasing hormone (GHRH) + arginine test. The initial dose of GH was 2 IU s.c. every other day, and was progressively increased to a maximum of 8 IU. Primary endpoint was N-acetylaspartate/(creatine + choline) (NAA/Cre + Cho) ratio in motor cortex assessed by magnetic resonance spectroscopy performed at months 0, 6, and 12. Secondary endpoints were mortality and ALS functional rating scale revised (ALSFRS-R). The NAA/(Cre + Cho) ratio decreased in all patients who completed the trial. No significant difference was noted between treated and placebo group. At baseline, although IGF-I levels were within the normal range, 73% of patients had GH deficiency, being severe in half of them. Compared with bulbar onset, spinal-onset patients showed more depressed GH response to the GHRH + arginine stimulation test (10.4 ± 7.0 versus 15.5 ± 8.1 ng/mL; p < 0.05). Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] increased from 2.1 ± 1.0 at baseline to 4.6 ± 1.9 at 12 months (p < 0.001). Insulin-like growth factor (IGF) binding protein 3 (IGFBP-3) decreased from 8,435 ± 4,477 ng/mL at baseline to 3,250 ± 1,780 ng/mL at 12 months (p < 0.001). The results show that GH exerted no effect on cerebral NAA or clinical

  20. Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10

    PubMed Central

    Varga, Jozsef L.; Schally, Andrew V.; Horvath, Judit E.; Kovacs, Magdolna; Halmos, Gabor; Groot, Kate; Toller, Gabor L.; Rekasi, Zoltan; Zarandi, Marta

    2004-01-01

    Antagonists of human growth hormone-releasing hormone (hGHRH) with increased potency and improved enzymatic and chemical stability are needed for potential clinical applications. We synthesized 21 antagonistic analogs of hGHRH(1-29)NH2, substituted at positions 8, 9, and 10 of the common core sequence {phenylacetyl-Tyr1, d-Arg2,28, para-chloro-phenylalanine 6, Arg9/homoarginine 9, Tyr10/O-methyltyrosine 10, α-aminobutyric acid 15, norleucine 27, Har29} hGHRH(1-29)NH2. Inhibitory effects on hGHRH-induced GH release were evaluated in vitro in a superfused rat pituitary system, as well as in vivo after i.v. injection into rats. The binding affinities of the peptides to pituitary GHRH receptors were also determined. Introduction of para-amidinophenylalanine 10 yielded antagonists JV-1-62 and -63 with the highest activities in vitro and lowest receptor dissociation constants (Ki = 0.057-0.062 nM). Antagonists JV-1-62 and -63 also exhibited the strongest effect in vivo, significantly (P < 0.05-0.001) inhibiting hGHRH-induced GH release for at least 1 h. Para-aminophenylalanine 10 and O-ethyltyrosine 10 substitutions yielded antagonists potent in vitro, but His10, 3,3′-diphenylalanine 10, 2-naphthylalanine 10, and cyclohexylalanine 10 modifications were detrimental. Antagonists containing citrulline 9 (in MZ-J-7-72), amidinophenylalanine 9 (in JV-1-65), His9, d-Arg9, citrulline 8, Ala8, d-Ala8, or α-aminobutyric acid 8 substituents also had high activity and receptor affinity in vitro. However, in vitro potencies of analogs with substitution in position 9 correlated poorly with acute endocrine effects in vivo, as exemplified by the weak and/or short inhibitory actions of antagonists JV-1-65 and MZ-J-7-72 on GH release in vivo. Nevertheless, antagonist JV-1-65 was more potent than JV-1-63 in tests on inhibition of the growth of human prostatic and lung cancer lines xenografted into nude mice. This indicates that oncological activity may be based on several mechanisms

  1. Human oocytes and preimplantation embryos express mRNA for growth hormone receptor.

    PubMed

    Ménézo, Y J; el Mouatassim, S; Chavrier, M; Servy, E J; Nicolet, B

    2003-11-01

    Human genetic expression of growth hormone receptor (GHR) gene was qualitatively analysed using reverse transcription polymerase chain reaction (RT-PCR) in cumulus cells, immature germinal vesicle (GV) and mature metaphase II (MII) stage oocytes and preimplantation human embryos. The transcripts encoding GHR were detected in cumulus cells and also in naked oocytes, either mature or not. In this case, a nested PCR is needed, as for early embryo preimplantation stages, before genomic activation. The GHR gene is highly expressed from the 4-day morula onwards. This suggests that GHR transcription follows a classical scheme associated with genomic activation. It is probable that, in human, growth hormone plays a role in the final stages of oocyte maturation and early embryogenesis as it does for several other mammalian species. PMID:15085728

  2. Fit-for-Purpose Radio Receptor Assay for the Determination of Growth Hormone Secretagogues in Urine.

    PubMed

    Ferro, P; Gutiérrez-Gallego, R; Bosch, J; Farré, M; Segura, J

    2015-12-01

    The everlasting pharmacological development is continuously producing new substances with potential doping abuse. Among these, secretagogues are very prone to misuse by athletes for their properties to release growth hormone (GH) and some limitations in the actual analytical methods to detect them. In this paper, an in-depth study on the key variables of the radio receptor method previously developed by our group is performed and a fit-for-purpose protocol is established. Thus, this sensitive and robust screening method is proposed as an intelligent and preventive antidoping method to detect new growth hormone secretagogues (GHSs) in exceptional suspicious urine samples obtained from athletes and will support the current detection methods based on liquid chromatography-mass spectrometry (LC-MS). PMID:26160832

  3. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 2; Hypothalamic Growth Hormone-Releasing Factor, Somatostatin Immunoreactivity, and Messenger RNA Levels in Microgravity

    NASA Technical Reports Server (NTRS)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1994-01-01

    Immunohistochemical analyses of hypothalamic hormones carried out on tissue from rats flown on an earlier flight (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. We found that staining in the median eminence for peptides that provide both stimulatory (growth hormone-releasing factor, or GRF) and inhibitory (somatostatin, SS) influences on growth hormone secretion were depressed in flight animals relative to synchronous controls, while staining for other neuroendocrine peptides, cortocotropin-releasing factor and arginine vasopressin, were similar in these two groups. While this suggests some selective impact of weightlessness on the two principal central nervous system regulators of growth hormone dynamics, the fact that both GRF- and SS-immunoreactivity (IR) appeared affected in the same direction is somewhat problematic, and makes tentative any intimation that effects on CNS control mechanisms may be etiologically significant contributors to the sequelae of reduced growth hormone secretion seen in prolonged space flight. To provide an additional, and more penetrating, analysis we attempted in hypothalamic material harvested from animals flown on Cosmos 2044 to complement immunohistochemical analyses of GRF and SS staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

  4. Hormonal regulatory role of eyestalk factors on growth of heart in mud crab, Scylla serrata

    PubMed Central

    Allayie, Sartaj Ahmad; Ravichandran, S.; Bhat, Bilal Ahmad

    2011-01-01

    The present study was attempted to know the growth regulation of eyestalk factors on the growth of heart in Scylla serrata using eyestalk extractions and bilateral eyestalk ablations. The bilateral eyestalk ablation led to the maximum growth indices of the heart ((H) indices) to 0.162 and 0.158 in ablated male and female, respectively, in comparison to 0.153 and 0.167 in the control male and female and 0.147 and 0.157 in injected male and female, respectively. The data have shown that the heart of male crabs grows faster than female crabs. The study has also shown that bilateral eyestalk ablation resulted in a significant increase in the heart indices in males and has least effect on the growth of the female heart. The results presented strongly support a potential role of the eyestalk factors and molting hormone regulating the growth of the heart in S. serrata. PMID:23961136

  5. Synthesis of bovine growth hormone in primates by using a herpesvirus vector.

    PubMed Central

    Desrosiers, R C; Kamine, J; Bakker, A; Silva, D; Woychik, R P; Sakai, D D; Rottman, F M

    1985-01-01

    A strain of herpesvirus saimiri containing a bovine growth hormone (bGH) gene under the control of the simian virus 40 (SV40) late-region promoter was constructed. This strain, bGH-Z20, was replication competent and stably harbored the bGH gene upon serial passage. Nonpermissive marmoset T cells persistently infected with bGH-Z20 produced a 0.9-kilobase RNA which contained all of the bGH exon sequences and appeared to initiate within the SV40 promoter region. However, in permissively infected owl monkey kidney cells, RNAs containing growth hormone sequences appeared to initiate from herpesvirus saimiri promoters positioned upstream from the SV40-growth hormone gene. Persistently infected T cells in culture secreted 500 ng of bGH protein per 10(6) cells per 24 h during the several months of testing. The secreted protein was 21 kilodaltons, the size of authentic bGH. New World primates experimentally infected with bGH-Z20 produced circulating bGH and developed immunoglobulin G antibodies directed against bGH. Because herpesviruses characteristically remain latent in the infected host, these observations suggest a means for replacing gene products missing or defective in hereditary genetic disorders. Images PMID:3016514

  6. Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method.

    PubMed

    Savari, Marzieh; Zarkesh Esfahani, Sayyed Hamid; Edalati, Masoud; Biria, Davoud

    2015-10-01

    Human growth hormone (hGH) is synthesized and stored by somatotroph cells of the anterior pituitary gland and can effect on body metabolism. This protein can be used to treat hGH deficiency, Prader-Willi syndrome and Turner syndrome. The limitations in current technology for soluble recombinant protein production, such as inclusion body formation, decrease its usage for therapeutic purposes. To achieve high levels of soluble form of recombinant human growth hormone (rhGH) we used suitable host strain, appropriate induction temperature, induction time and culture media composition. For this purpose, 32 experiments were designed using Taguchi method and the levels of produced proteins in all 32 experiments were evaluated primarily by ELISA and dot blotting and finally the purified rhGH protein products assessed by SDS-PAGE and Western blotting techniques. Our results indicate that media, bacterial strains, temperature and induction time have significant effects on the production of rhGH. The low cultivation temperature of 25°C, TB media (with 3% ethanol and 0.6M glycerol), Origami strain and a 10-h induction time increased the solubility of human growth hormone. PMID:26151869

  7. Hypertrophic scars in a patient with Turner's syndrome treated with recombinant growth hormone.

    PubMed

    Kędzia, Andrzej; Pawlaczyk, Mariola; Petriczko, Elżbieta

    2014-05-01

    Turner's syndrome is a common genetic disorder of girls and women, for which characteristic clinical symptoms encompass short stature, gonadal dysgenesis, systemic defects, multiple dysmorphic features and skin changes, including an increased number of melanocytic nevi, hypertrophic scars and keloids. The affected girls are treated with recombinant human growth hormone to improve the height. We present a case of a 15-year-old girl with Turner's syndrome, hypertrophic scars and a keloid. At the age of 12 years and 8 months, the girl started recombinant human growth hormone treatment. During the therapy, a surgical excision of 4 out of 42 benign melanocytic nevi was performed. After 2 months the hypertrophic scars as well as a keloid were noted at sites of excision. Parents of girls with Turner's syndrome undertake various attempts to improve not only the height and maturity of their daughters, but also their appearance by commonly performed surgical corrections of the webbed neck and pigmented nevi. The presented case suggests an increased risk of scars hypertrophy and keloid formations after surgical intervention in Turner's syndrome patients who are treated with recombinant human growth hormone at the same time. Due to that it should be advised to postpone all planned surgical procedures until the therapy has been completed. PMID:25097479

  8. Educating children and families about growth hormone deficiency and its management: part 1.

    PubMed

    Collin, Jacqueline; Whitehead, Amanda; Walker, Jenny

    2016-02-01

    The management of growth hormone deficiency is long term. Children may be diagnosed at pre-school age meaning relationships with the paediatric endocrine team may last more than 15 years. The education role of the paediatric endocrine nurse specialist is essential in working in partnership with families over a long period of time. Children and young people have changing needs for information to help them understand their condition and growth hormone deficiency treatment as they grow up. Developing positive working relationships with parents, children and young people enables their developmental needs and the context in which they live their lives to be central to any educational planning for them. Addressing developmental needs when providing information on growth hormone deficiency to children and young people reinforces the need for education to be an ongoing process and not a one-off event. This is part one of a two-part article. The second part will be published in the March issue of Nursing Children and Young People and it focuses on educating children, young people and their parents about the condition, and includes case studies. PMID:26856576

  9. Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients.

    PubMed Central

    Wolf, R F; Pearlstone, D B; Newman, E; Heslin, M J; Gonenne, A; Burt, M E; Brennan, M F

    1992-01-01

    The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient. PMID:1417177

  10. 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. PMID:22829397

  11. 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.

  12. [Construction of human growth hormone lentiviral vector and its expression in murine skeletal myoblasts].

    PubMed

    Liu, Xiang-Yang; Lu, Yong-Xin; Xu, Yu-Lan; Li, Xiao-Qing; Liu, Juan; Li, Ai-Hua; Luo, Ping; Wan, Jian-Ping

    2006-03-01

    The aim of this study is to construct a lentiviral vector encoding human growth hormone, and to achieve the long, efficient and stable expression in murine skeletal myoblasts. Primary skeletal myoblasts were isolated from Sprague-Dawley rats and cultured by enzymatic digestion. We tested them by Desmin immunohistochemistry stains and found their viability was up to 94% by Trypan blue. Human growth hormone (hGH) cDNA was subcloned into expression vector pLenti6/V5-D-TOPO to construct recombinant pLenti6/V5-hGH. The pLenti6/V5-hGH and the contructed pLenti6/V5-EGFP were transfected into murine skeletal myoblasts by the Lipofectamin 2000. Through counting by the Confocal Laser Scanning Microscope, we identified the transfection efficency. We added the blasticidin to the 6-well plate with lids and obtained stable myoblasts expressing hGH. The concentration of human growth hormone (hGH) in cell culture medium was detected by Radioimmunoassay (RIA). Polymerase Chain Reaction (PCR) and DNA sequence showed hGH cDNA had been correctly inserted into pLenti6/V5-D-TOPO vector. Bright green fluorescence of the transfected cells could be observed under the Confocal Laser Scanning Microscope after 24 h transfection with pLenti6/V5-EGFP plasmids, and the transfection rate reached 40%. The difference was distinct (P < 0.01) between the pLenti6/V5- hGH groups and control groups in the secretive level of human growth hormone. After 8 weeks, the expression of human growth hormone was still stable. Then, we validated the biological characterization of the rhGH by the enzyme-link immunosorbent assay (ELISA) of the Insulin-like growth factor I (IGF-1). These results demonstrate we have successfully constructed the recombinant pLenti6/V5-hGH plasmids and accomplished rhGH long, efficient and stable expression ectopic in skeletal muscle myoblasts. PMID:16607951

  13. 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. PMID:17376444

  14. Growth control of prostatic carcinoma cells in serum-free media: interrelationship of hormone response, cell density, and nutrient media.

    PubMed Central

    Kaighn, M E; Kirk, D; Szalay, M; Lechner, J F

    1981-01-01

    Two established prostatic carcinoma cell lines have been grown in long-term culture in a defined medium (PFMR-4) free of serum, hormones, or growth factors. Growth of both lines in serum-free medium was population dependent. This cell-density requirement could be replaced by mitomycin C-inactivated feeder cells, homologous conditioned medium, or fetal bovine serum, but not by hormones or growth factors. The cells responded to these factors only at high density. The nature of this hormonal response was dependent on the kind of basal nutrient medium used. Growth in PFMR-4 with added insulin was more rapid than that in DME/F12 medium with any combination of hormones or growth factors and was substantially greater than growth in DME/F12 medium with insulin alone. The results demonstrate that whereas these two prostatic carcinoma lines (PC-3 and DU 145) do not require hormones for survival or growth, they do respond to certain hormones under appropriate conditions. These conditions include both the type of basal nutrient medium used and the population density. PMID:7029542

  15. Identification of the growth hormone-releasing hormone analogue [Pro1, Val14]-hGHRH with an incomplete C-term amidation in a confiscated product.

    PubMed

    Esposito, Simone; Deventer, Koen; Van Eenoo, Peter

    2014-01-01

    In this work, a modified version of the 44 amino acid human growth hormone-releasing hormone (hGHRH(1-44)) containing an N-terminal proline extension, a valine residue in position 14, and a C-terminus amidation (sequence: PYADAIFTNSYRKVVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 ) has been identified in a confiscated product by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Investigation of the product suggests also an incomplete C-term amidation. Similarly to other hGHRH analogues, available in black markets, this peptide can potentially be used as performance-enhancing drug due to its growth hormone releasing activity and therefore it should be considered as a prohibited substance in sport. Additionally, the presence of partially amidated molecule reveals the poor pharmaceutical quality of the preparation, an aspect which represents a big concern for public health as well. PMID:25283153

  16. A critical synopsis: Continuous growth of proximal tubular kidney epithelial cells in hormone-supplemented serum-free medium

    NASA Technical Reports Server (NTRS)

    Chuman, L. M.; FINE; COHEN; Saier, M. H.

    1985-01-01

    The kidney forms urine and reabsorbs electrolytes and water. Kidney cell lines and hormone supplemented serum free medium were used for growth. The hormones were insulin, transferrin, vasopressin, cholesterol, prostaglandins, hydrocortisone, and triidothyronine. Epithelial cell lines are polar and form hemicysts. The Madin-Darby canine kidney(MDCK) cell line used is distal tubulelike. LLC-PK sub 1 cells are derived from pig kidneys and have the properties of different kidney segments. The LLC-PK sub 1 cells with proximal tubule properties were maintained in hormone-supplemented serum free medium. Seven factors (the aforementioned homrones and selenium) were needed for growth. Hormone-defined medium supported LLC-PK sub 1 cell growth, allowed transport (as seen by hemicyst formation), and influenced cell morphology. Vasopressin (used for growth and morphology) could be partially replaced by isobutylmethylxanthine or dibutyryl cAMP. The defined medium was used to isolate rabbit proximal tubule kidney epithelial cells free of fibroblasts.

  17. Beneficial Effects of Long-Term Growth Hormone Treatment on Adaptive Functioning in Infants With Prader-Willi Syndrome.

    PubMed

    Lo, Sin T; Festen, Dederieke A M; Tummers-de Lind van Wijngaarden, Roderick F A; Collin, Philippe J L; Hokken-Koelega, Anita C S

    2015-07-01

    The aim of this study was to investigate the effect of growth hormone treatment on adaptive functioning in children with Prader-Willi syndrome. Vineland Adaptive Behavior Scale (VABS) was assessed during a randomized controlled trial (RCT) and after 7 years of growth hormone treatment. In the RCT, 75 children (42 infants and 33 prepubertal children) with Prader-Willi syndrome were included. Subsequently, 53 children were treated with long-term growth hormone. Our study demonstrates a marked delay in adaptive functioning in infants and children with Prader-Willi syndrome, which was associated with older age and lower intelligence. Results of the repeated measurements show that the earlier growth hormone treatment was started during infancy, the better the adaptive skills were on the long-term. PMID:26161469

  18. Rearing Mozambique tilapia in tidally-changing salinities: Effects on growth and the growth hormone/insulin-like growth factor I axis.

    PubMed

    Moorman, Benjamin P; Yamaguchi, Yoko; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2016-08-01

    The growth hormone (GH)/insulin-like growth factor (IGF) axis plays a central role in the regulation of growth in teleosts and has been shown to be affected by acclimation salinity. This study was aimed at characterizing the effects of rearing tilapia, Oreochromis mossambicus, in a tidally-changing salinity on the GH/IGF axis and growth. Tilapia were raised in fresh water (FW), seawater (SW), or in a tidally-changing environment, in which salinity is switched between FW (TF) and SW (TS) every 6h, for 4months. Growth was measured over all time points recorded and fish reared in a tidally-changing environment grew significantly faster than other groups. The levels of circulating growth hormone (GH), insulin-like growth factor I (IGF-I), pituitary GH mRNA, gene expression of IGF-I, IGF-II, and growth hormone receptor 2 (GHR) in the muscle and liver were also determined. Plasma IGF-I was higher in FW and TS than in SW and TF tilapia. Pituitary GH mRNA was higher in TF and TS than in FW and SW tilapia. Gene expression of IGF-I in the liver and of GHR in both the muscle and liver changed between TF and TS fish. Fish growth was positively correlated with GH mRNA expression in the pituitary, and GHR mRNA expression in muscle and liver tissues. Our study indicates that rearing fish under tidally-changing salinities elicits a distinct pattern of endocrine regulation from that observed in fish reared in steady-state conditions, and may provide a new approach to increase tilapia growth rate and study the regulation of growth in euryhaline fish. PMID:27032617

  19. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 1; Growth Hormone Regulation Synthesis and Secretion in Microgravity

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R.; Vale, W.; Sawchenko, P.; Ilyina-Kakueva, E. I.

    1994-01-01

    Changes in the musculoskeletal, immune, vascular, and endocrine system of the rat occur as a result of short-term spaceflight. Since pituitary gland growth hormone (GH) plays a role in the control of these systems, and since the results of an earlier spaceflight mission (Spacelab 3, 1985) showed that GH cell function was compromised in a number of post-flight tests, we repeated and extended the 1985 experiment in two subsequent spaceflights: the 12.5 day mission of Cosmos 1887 (in 1987) and the 14 day mission of Cosmos 2044 (in 1989). The results of these later two flight experiments are the subject of this report. They document repeatable and significant changes in the GH cell system of the spaceflown rat in several post-flight tests.

  20. Effects of recombinant human growth hormone on anorexic Nile crocodiles (Crocodylus niloticus).

    PubMed

    Kimwele, C N; Kanui, T I; Aulie, A

    1992-07-01

    1. Eleven-month-old Nile crocodiles with poor appetite and retarded growth were injected with 0.325 micrograms/g recombinant human growth hormone (hGH) twice a week for 4 weeks. 2. The treated animals had a mean intake per meal of 29.8 g/kg, while the controls ate only 2.8 g/kg. 3. The treated group gained 8.1% of their initial body weight, while the controls lost 6.3%. 4. During 4 weeks of treatment the body and head length increased by 3.93 and 1.29%, respectively, while no linear growth took place in the controls. 5. The treated group had higher contents of skeletal muscle protein and liver glycogen than the control group. 6. In conclusion, recombinant hGH induces appetite and growth in anorexic crocodiles. PMID:1359943

  1. Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom.

    PubMed Central

    Buchanan, C R; Preece, M A; Milner, R D

    1991-01-01

    OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review. PMID:2025705

  2. 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...

  3. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction

    PubMed Central

    Czikora, Istvan; Sridhar, Supriya; Gorshkov, Boris; Alieva, Irina B.; Kasa, Anita; Gonzales, Joyce; Potapenko, Olena; Umapathy, Nagavedi S.; Pillich, Helena; Rick, Ferenc G.; Block, Norman L.; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Schally, Andrew V.; Lucas, Rudolf

    2014-01-01

    Rationale: Antibiotic treatment of patients infected with G− or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion. Methods: Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting. Results: GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions: GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the

  4. Short term response of insulin, glucose, growth hormone and corticosterone to acute vibration in rats.

    NASA Technical Reports Server (NTRS)

    Dolkas, C. B.; Leon, H. A.; Chackerian, M.

    1971-01-01

    Study carried out to obtain some notion of the initial phasing and interactive effects among some hormones known to be responsive to vibration stress. Sprague-Dawley derived rats were exposed to the acute effects of confinement and confinement with lateral (plus or minus G sub y) vibration. The coincident monitoring of glucose, insulin, growth hormone, and corticosterone plasma levels, during and immediately subsequent to exposure to brief low level vibration, exhibits the effects of inhibition of insulin release by epinephrine. The ability of insulin (IRI) to return rapidly to basal levels, from appreciably depressed levels during vibration, in the face of elevated levels of glucose is also shown. Corticosterone responds with almost equal rapidity, but in opposite phase to the IRI. The immuno-assayable growth hormone (IGH) dropped from a basal level of 32 ng/ml to 7.3 ng/ml immediately subsequent to vibration and remained at essentially that level throughout the experiment (60 min). Whether these levels represent a real fall in the rat or whether they merely follow the immuno-logically deficient form is still in question.

  5. Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease

    PubMed Central

    Onori, Paolo; Mancinelli, Romina; Franchitto, Antonio; Carpino, Guido; Renzi, Anastasia; Brozzetti, Stefania; Venter, Julie; Francis, Heather; Glaser, Shannon; Jefferson, Douglas M.; Alpini, Gianfranco; Gaudio, Eugenio

    2014-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle-stimulating hormone (FSH) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation (BDL). Aims To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models. Methods Evaluation of FSH receptor (FSHR), FSH, phospho-extracellular-regulated kinase (pERK) and c-myc expression in liver fragments from normal patients and patients with ADPKD. In vitro, we studied proliferating cell nuclear antigen (PCNA) and cAMP levels in a human immortalized, non-malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD (LCDE) with or without transient silencing of the FSH gene. Results Follicle-stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p-ERK and c-myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway. Conclusion These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD. PMID:23617956

  6. Yolk hormones influence in ovo chemosensory learning, growth, and feeding behavior in domestic chicks.

    PubMed

    Bertin, Aline; Meurisse, Maryse; Arnould, Cécile; Leterrier, Christine; Constantin, Paul; Cornilleau, Fabien; Vaudin, Pascal; Burlot, Thierry; Delaveau, Joel; Rat, Christophe; Calandreau, Ludovic

    2016-03-01

    In this study, we assessed whether prenatal exposure to elevated yolk steroid hormones can influence in ovo chemosensory learning and the behavior of domestic chicks. We simulated a maternal environmental challenge by experimentally enhancing yolk progesterone, testosterone, and estradiol concentrations in hen eggs prior to incubation. The embryos from these hormones-treated eggs (HO) as well as sham embryos (O) that had received the vehicle-only were exposed to the odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group of control embryos (C) was not exposed to the odor. All chicks were tested following hatching for their feeding preferences between foods that were or were not odorized with the menhaden odor. In the 3-min choice tests, the behavior of O chicks differed significantly according to the type of food whereas C and HO chicks showed no preference between odorized and non-odorized food. Our result suggests weaker response in HO chicks. In addition, HO chicks showed impaired growth and reduced intake of an unfamiliar food on the 24-h time scale compared to controls. Our data suggest that embryonic exposure to increased yolk hormone levels can alter growth, chemosensory learning, and the development of feeding behaviors. PMID:26419601

  7. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    SciTech Connect

    Ramasharma, K.; Li, C.H.

    1987-05-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and ..cap alpha..-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin.

  8. Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

    PubMed

    Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

    2013-03-01

    Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in

  9. Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns.

    PubMed Central

    Herndon, D N; Hawkins, H K; Nguyen, T T; Pierre, E; Cox, R; Barrow, R E

    1995-01-01

    BACKGROUND: Human growth hormone is an anabolic agent that attenuates injury-induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up-regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering > 40% of total body surface area. OBJECTIVE: The authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. METHODS: Ten massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. RESULTS: Donor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. CONCLUSION: Results indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural

  10. Thyroxine modifies the effects of growth hormone in Ames dwarf mice.

    PubMed

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M

    2015-04-01

    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early-life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity. PMID:25935838

  11. PIF4 Integrates Multiple Environmental and Hormonal Signals for Plant Growth Regulation in Arabidopsis

    PubMed Central

    Choi, Hyunmo; Oh, Eunkyoo

    2016-01-01

    As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth. PMID:27432188

  12. PIF4 Integrates Multiple Environmental and Hormonal Signals for Plant Growth Regulation in Arabidopsis.

    PubMed

    Choi, Hyunmo; Oh, Eunkyoo

    2016-08-31

    As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth. PMID:27432188

  13. Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term.

    PubMed Central

    Spencer, J. A.; Chang, T. C.; Jones, J.; Robson, S. C.; Preece, M. A.

    1995-01-01

    Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical venous blood after delivery of 78 term newborn infants. Three groups of pregnancies were prospectively identified during the third trimester, according to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans. Fetal size was considered either appropriate for gestational age (AGA) or small for gestational age (SGA), according to whether the first ultrasound measurement of abdominal circumference was equal to or above, or below the tenth centile for gestational age, respectively. Subsequent fetal growth was quantified by the change in the standard deviation score of abdominal circumference measurements between the first and last scans before delivery. Fetal growth retardation (FGR) was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range 0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13 (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median 0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group with normal growth was also significantly lower than that of the AGA group with normal growth. There were no significant differences in IGFBP-1 or GH concentrations between the three groups. These observations indicate that umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate to both fetal size and fetal growth during the third trimester of pregnancies reaching term. PMID:7583612

  14. Influences of the environment on the endocrine and paracrine fish growth hormone-insulin-like growth factor-I system.

    PubMed

    Reinecke, M

    2010-04-01

    Insulin-like growth factor-I (IGF-I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF-I gene is mainly expressed in the liver that represents the principal source of endocrine IGF-I but also in numerous other organs where the hormone most probably acts in an autocrine-paracrine manner. The primary stimulus for synthesis and release of IGF-I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish 'GH-IGF-I axis'. The GH-IGF-I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF-I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF-I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH-IGF-I research are analysed and future focuses are suggested at the end of the sections. PMID:20537012

  15. Hypothalamic expression of human growth hormone induces post-pubertal hypergonadotrophism in male transgenic growth retarded rats.

    PubMed

    Davies, J S; Thompson, N M; Christian, H C; Pinilla, L; Ebling, F J P; Tena-Sempere, M; Wells, T

    2006-10-01

    Growth hormone (GH) is known to regulate peripheral components of the hypothalamo-pituitary gonadal (HPG) axis, but it remains unclear whether GH exerts a significant influence on the activity of the hypothalamo-pituitary components of the HPG axis. In this study, we investigated the development of HPG axis function in the male transgenic growth retarded (Tgr) rat, a model of moderate systemic GH deficiency caused by hypothalamic expression of human (h)GH. Impaired postnatal somatotroph expansion and moderate GH deficiency in male Tgr rats were accompanied by a two- to three-fold increase in pituitary gonadotrophin content, but without a significant change in the pituitary gonadotroph population. A three- to nine-fold elevation in basal circulating luteinising hormone concentration was seen in postpubertal Tgr rats, with a smaller increase in follicle-stimulating hormone. Despite this hypergonadotrophism, there was no corresponding increase in steroidogenic (circulating testosterone and seminal vesicle weights) or gametogenic (spermatozoa counts in seminiferous tubules) activity in the postpubertal Tgr testis. Following puberty, the plasma leptin concentration also became progressively elevated in Tgr males. Circulating gonadotrophin and leptin levels were normalised in Tgr rats by peripheral physiological replacement of rat GH, but plasma testosterone concentration was unaffected. These results confirm that hGH exerts a positive influence on the central control of gonadotrophin secretion in the Tgr rat, but the absence of a corresponding elevation in the steroidogenic or gametogenic function of the Tgr testis implies that the peripheral GH/insulin-like growth factor I axis may also exert a permissive influence on testicular function. The relative contribution of somatogenic and lactogenic mechanisms and the potential influence of elevated leptin and decreased sensitivity to androgen feedback to the development of postpubertal hypergonadotrophism in Tgr males

  16. Synthesis and biological evaluation of antagonists of growth hormone-releasing hormone with high and protracted in vivo activities

    PubMed Central

    Varga, József L.; Schally, Andrew V.; Csernus, Valér J.; Zarándi, Márta; Halmos, Gábor; Groot, Kate; Rékási, Zoltán

    1999-01-01

    Some antagonists of human growth hormone-releasing hormone (hGH-RH) synthesized previously were shown to inhibit in vivo proliferation of various human cancers in nude mice. However, the activity of these analogs requires an increase to assure clinical efficacy. In an attempt to prepare hGH-RH antagonists with a high and protracted activity, we synthesized and biologically tested 22 antagonistic analogs of hGH-RH(1–29)NH2. The ability of the antagonists to inhibit hGH-RH-induced GH release was evaluated in vitro in a superfused rat pituitary system, as well as in vivo after i.v. injection into rats. The binding affinity of the peptides to GH-RH receptors also was determined. All antagonistic analogs had the common core sequence [PhAc-Tyr1,d-Arg2, Phe(4-Cl)6 (para-chlorophenylalanine), Abu15 (α-aminobutyric acid),Nle27]hGH-RH(1–29)NH2 and contained Arg, d-Arg, homoarginine (Har), norleucine (Nle), and other substitutions. The following analogs were determined to have a high and/or protracted antagonistic activity: [PhAc-Tyr1,d-Arg2,Phe(4-Cl)6,Arg9,Abu15,Nle27,d-Arg29]hGH-RH(1–29)NH2 (JV-1–10), [PhAc-Tyr1,d-Arg2,Phe(4-Cl)6,Abu15,Nle27,d-Arg28,Har29]hGH-RH(1–29)NH2 (MZ-6–55), [PhAc-Tyr1,d-Arg2,Phe(4-Cl)6,Arg9,Abu15,Nle27,d-Arg28,Har29]hGH-RH(1–29)NH2 (JV-1–36), and [PhAc-Tyr1,d-Arg2,Phe(4-Cl)6,Har9,Tyr(Me)10,Abu15,Nle27,d-Arg28,Har29]hGH-RH(1–29)NH2 (JV-1–38). Among the peptides tested, analog JV-1–36 showed the highest GH-RH antagonistic activity in vitro and also induced a strong and prolonged inhibition of GH release in vivo for at least 30 min. The antagonist JV-1–38 was slightly less potent than JV-1–36 both in vitro and in vivo but proved to be very long-acting in vivo, suppressing the GH-RH-induced GH release even after 60 min. High and protracted in vivo activities of these antagonists indicate an improvement over earlier GH-RH analogs. Some of these hGH-RH antagonists could find clinical applications in the treatment of cancers

  17. Leucine Supplementation Improves Acquired Growth Hormone Resistance in Rats with Protein-Energy Malnutrition

    PubMed Central

    Wang, Xinying; Zhao, Jie; Wan, Xiao; Zhang, Li; Wu, Chao; Li, Ning; Li, Jieshou

    2015-01-01

    Background Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition. Methodology/Principal Findings Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in

  18. Growth Hormone and Reproduction: A Review of Endocrine and Autocrine/Paracrine Interactions

    PubMed Central

    Hull, Kerry L.; Harvey, Steve

    2014-01-01

    The somatotropic axis, consisting of growth hormone (GH), hepatic insulin-like growth factor I (IGF-I), and assorted releasing factors, regulates growth and body composition. Axiomatically, since optimal body composition enhances reproductive function, general somatic actions of GH modulate reproductive function. A growing body of evidence supports the hypothesis that GH also modulates reproduction directly, exerting both gonadotropin-dependent and gonadotropin-independent actions in both males and females. Moreover, recent studies indicate GH produced within reproductive tissues differs from pituitary GH in terms of secretion and action. Accordingly, GH is increasingly used as a fertility adjunct in males and females, both humans and nonhumans. This review reconsiders reproductive actions of GH in vertebrates in respect to these new conceptual developments. PMID:25580121

  19. 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

  20. 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

  1. Growth and changes of endogenous hormones of mulberry roots in a simulated rocky desertification area.

    PubMed

    Feng, Dalan; Huang, Xiaohui; Liu, Yun; Willison, J H Martin

    2016-06-01

    We studied the growth of roots of white mulberry (Morus alba) trees in response to different water and nutrient conditions in sets of three or five containers connected via small pipes and arranged so as to simulate the heterogeneous soil conditions associated with rocky desertification. The experiment was conducted to improve understanding of the adaptation of M. alba to this stressful environment. The trees were grown for a year under constant water and nutrient conditions in the soils within each container of any set of containers. Differences in root activity and endogenous hormones within root tips were measured at the end of the experiment. We compared four treatment groups: H (variable moisture among containers), F (variable nutrients among containers), HF (both moisture and nutrients varied among containers), and CK (non-varied control). Results showed the following: (1) Mulberry roots showed obvious hydrotropic and chemotropic growth patterns, but chemotropism did not occur in the condition of water shortage. (2) Measurement of growth indices (root surface area, total root length, number of root tips, root biomass) showed that growth status was best in group HF once the roots were able to access containers with sufficient water and nutrients, followed by group H. The indices were significantly poorer in groups F and CK. (3) The content of auxin, cytokinin, and gibberellins in roots under soil drought conditions were lower than under wetter soil conditions. In contrast, abscisic acid content and root activity were higher under soil drought conditions than under wetter soil conditions. The results indicated that water is the key factor restricting growth of white mulberry trees in areas of rocky desertification but that the trees adjust endogenous hormones in their roots to promote tropic growth and obtain sufficient moisture and nutrients over the long term. Moreover, under long-term drought stress conditions, mulberry trees retained high root activity

  2. Favorable Growth Hormone Treatment Response in a Young Boy with Achondroplasia

    PubMed Central

    Krstevska-Konstantinova, Marina; Stamatova, Ana; Gucev, Zoran

    2016-01-01

    Background: Achondroplasia is a skeletal dysplasia, the most common cause of rhizomelic dwarfism. Case presentation: This is a ten year old boy who was first diagnosed prenatally. He had a mutation c1138G>A in the gene FGFR3 in a heterozygotic constellation. His IGF1 and IGFBP3 levels were normal. Two stimulation tests for growth hormone were performed with values within the reference range. His psychomotor development was adequate for his age except for speech difficulty. He started with recombinant hGH (r-hGH) at the age of 3.4 years in a dose of 0.06 mg/kg. His mean Height SDS (HtSDS) was -2.2. Results: The growth increased to 10 cm/year in the first year of therapy (HtSDS -1.1). It decreased during the second year to 4 cm (HtSDS -1.7) and again increased during the third year to 8 cm/year (HtSDS–1.3). In the next years the growth was constant (6.5, 2.3, 3.5 cm / year). He is still growing in the 3rd percentile of the growth curve (HtSDS – 1.2) under GH treatment. The body disproportion remained the same. Conclusion: The growth response on GH treatment was satisfactory in the first 4 years of treatment, and the boy still continued to grow. The young age at the start of treatment was also of importance. Our other patients with achondroplasia who started treatment older had a poor response to growth hormone. PMID:27147792

  3. Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin.

    PubMed

    Carlsson, L; Nilsson, I; Oscarsson, J

    1998-06-01

    Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to

  4. Efficacy and safety of growth hormone treatment for children born small for gestational age

    PubMed Central

    2014-01-01

    Recombinant growth hormone (GH) is an effective treatment for short children who are born small for gestational age (SGA). Short children born SGA who fail to demonstrate catch-up growth by 2-4 years of age are candidates for GH treatment initiated to achieve catch-up growth to a normal height in early childhood, maintain a normal height gain throughout childhood, and achieve an adult height within the normal target range. GH treatment at a dose of 35-70 µg/kg/day should be considered for those with very marked growth retardation, as these patients require rapid catch-up growth. Factors associated with response to GH treatment during the initial 2-3 years of therapy include age and height standard deviation scores at the start of therapy, midparental height, and GH dose. Adverse events due to GH treatment are no more common in the SGA population than in other conditions treated with GH. Early surveillance in growth clinics is strongly recommended for children born SGA who have not caught up. Although high dose of up to 0.067 mg/kg/day are relatively safe for short children with growth failure, clinicians need to remain aware of long-term mortality and morbidity after GH treatment. PMID:25324863

  5. Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

    NASA Technical Reports Server (NTRS)

    Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

  6. Terminal Oxidases of Bacillus subtilis Strain 168: One Quinol Oxidase, Cytochrome aa3 or Cytochrome bd, Is Required for Aerobic Growth

    PubMed Central

    Winstedt, Lena; von Wachenfeldt, Claes

    2000-01-01

    The gram-positive endospore-forming bacterium Bacillus subtilis has, under aerobic conditions, a branched respiratory system comprising one quinol oxidase branch and one cytochrome oxidase branch. The system terminates in one of four alternative terminal oxidases. Cytochrome caa3 is a cytochrome c oxidase, whereas cytochrome bd and cytochrome aa3 are quinol oxidases. A fourth terminal oxidase, YthAB, is a putative quinol oxidase predicted from DNA sequence analysis. None of the terminal oxidases are, by themselves, essential for growth. However, one quinol oxidase (cytochrome aa3 or cytochrome bd) is required for aerobic growth of B. subtilis strain 168. Data indicating that cytochrome aa3 is the major oxidase used by exponentially growing cells in minimal and rich medium are presented. We show that one of the two heme-copper oxidases, cytochrome caa3 or cytochrome aa3, is required for efficient sporulation of B. subtilis strain 168 and that deletion of YthAB in a strain lacking cytochrome aa3 makes the strain sporulation deficient. PMID:11073895

  7. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Abnormal Placentation and Fetal Growth1

    PubMed Central

    Mainigi, Monica A.; Olalere, Devvora; Burd, Irina; Sapienza, Carmen; Bartolomei, Marisa; Coutifaris, Christos

    2013-01-01

    ABSTRACT Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatment-induced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism(s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes. PMID:24352558

  8. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence.

    PubMed

    Murray, P G; Dattani, M T; Clayton, P E

    2016-01-01

    Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended. PMID:26153506

  9. Effects of recombinant human growth hormone in patients with severe sepsis.

    PubMed Central

    Voerman, H J; van Schijndel, R J; Groeneveld, A B; de Boer, H; Nauta, J P; van der Veen, E A; Thijs, L G

    1992-01-01

    The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment. PMID:1466618

  10. Sex steroid and growth hormone supplementation to enhance performance in adolescent athletes.

    PubMed

    Rogol, A D

    2000-08-01

    Ergogenic aids are taken to enhance energy utilization by producing more, controlling its use, or increasing mechanical efficiency. Most athletes are looking toward enhancing performance by proper training modalities and methods; however, some look to the biochemical route for a "quick fix." Thus, the use of chemical agents is on the rise. Herein is provided information on the anabolic-androgenic agents androstenedione, dehydroepiandrosterone, and the "parent" compound, testosterone. The former two, at best, have equivocal activity, but testosterone is both anabolic and androgenic in doses that adolescents might receive. Growth hormone and insulin-like growth factor-1 are anabolic, nonandrogenic compounds with undoubted effects on the lean body mass compartment. Both are expensive, not readily available, and subject to the art of counterfeiting. Thus, very few data are available in non-growth hormone-deficient adolescents. The discussion of these agents ends with issues of fairness, ethics, and the message we attempt to project to our teenagers, whether athletes or not. PMID:10943821

  11. The mechanism by which an asymmetric distribution of plant growth hormone is attained

    NASA Astrophysics Data System (ADS)

    Bandurski, Robert S.; Schulze, Aga; Jensen, Philip; Desrosiers, Mark; Epel, Bernard; Kowalczyk, Stanley

    Zea mays (sweet corn) seedlings attain an asymmetric distribution of the growth hormone indole-3-acetic acid (IAA) within 3 minutes following a gravity stimulus. Both free and esterified IAA (that is total IAA) accumulate to a greater extent in the lower half of the mesocotyl cortex of a horizontally placed seedling than in the upper half. Thus, changes in the ratio of free IAA to ester IAA cannot account for the asymmetric distribution. Our studies demonstrate there is no de novo synthesis of IAA in young seedlings. We conclude that asymmetric IAA distribution is attained by a gravity-induced, potential-regulated gating of the movement of IAA from kernel to shoot and from stele to cortex. As a working theory, which we call the Potential Gating Theory, we propose that perturbation of the plant's bioelectric field, induced by gravity, causes opening and closing of transport channels in the plasmodesmata connecting the vascular stele to the surrounding cortical tissues. This results in asymmetric growth hormone distribution which results in the asymmetric growth characteristic of the gravitropic response.

  12. Traditional and novel aspects of the metabolic actions of growth hormone.

    PubMed

    Sperling, Mark A

    2016-06-01

    Growth hormone has been known to be diabetogenic for almost a century and it's diabetogenic properties fostered consideration of excessive and abnormal GH secretion as a cause of diabetes, as well as a role in the microvascular complications, especially retinopathy. However, besides inducing insulin resistance, GH also is lipolytic and a major anabolic hormone for nitrogen retention and protein synthesis. These actions are best illustrated at the extremes of GH secretion: Gigantism/acromegaly is characterized by excessive growth, CHO intolerance, hyperplasia of bone, little body fat and prominent muscle development, whereas total deficiency of GH secretion or action is associated with adiposity, poor growth, and poor muscle development. These actions also become apparent during puberty and pregnancy, times when GH secretion is increased and account for the characteristic changes in body composition and tendency to diabetes. More recently, tissue specific deletions of the GH receptor (GHR), have uncovered newer metabolic effects including it's essential role in triglyceride export from the liver when GHR is deleted in the liver, leading to hepatic steatosis and ultimately to hepatic adenoma formation, effects which may explain these findings in obesity, a state of diminished GH secretion and action. In addition deletion of GH action in muscle and fat is associated with specific patterns of disturbed phenotype and metabolic effects in CHO, fat, and protein metabolism affecting the specific tissue and whole body function. This chapter provides an overview of these classic and newer metabolic functions of GH, placing this hormone and its actions in a central role of body fuel economy in health and disease. PMID:26194064

  13. Effects of high selenium and fat supplementation on growth performance and thyroid hormones concentration of broilers.

    PubMed

    Chadio, Stella E; Pappas, Athanasios C; Papanastasatos, Anastasios; Pantelia, Dionysia; Dardamani, Aikaterini; Fegeros, Konstantinos; Zervas, George

    2015-01-01

    A total of 400, as hatched, broilers were used to investigate the effect of increase of selenium and energy intake on thyroid hormone metabolism, growth and liver fatty acid profile. There were 5 replicates of 4 dietary treatments namely, TA (0.289mg Se per kg diet and adequate energy content), TB (0.583mg Se per kg diet and adequate energy content), TC (0.267mg Se per kg diet and 9% increase of energy content) and TD (0.576mg Se per kg diet and 9% increase of energy content). Diets were isonitrogenous. Zinc L-selenomethionine complex was used to increase Se content and corn oil was used to increase the energy content. The experiment lasted 42 days. Broiler growth performance was not significantly affected by dietary treatments. Liver glutathione peroxidase (GPx) activity increased (P<0.05) in broilers fed high Se and energy diets compared to other ones. Whole blood GPx activity was higher in Se supplemented groups however, it was reduced by age. Thyroid hormone concentrations were unaffected by dietary treatments. A significant increase of linoleic and arachidonic acid concentration (P<0.001) was observed in the liver of broilers fed diets with moderately increased energy content and supplemented with Se compared to those fed diets with moderately increased energy content alone. In conclusion, zinc L-selenomethionine complex and moderate increase of energy content did not affect growth rate or thyroid hormone metabolism but led to increased liver fatty acid content and hepatic GPx activity. PMID:25447588

  14. Growth Hormone Regulates the Balance Between Bone Formation and Bone Marrow Adiposity

    PubMed Central

    Menagh, Philip J; Turner, Russell T; Jump, Donald B; Wong, Carmen P; Lowry, Malcolm B; Yakar, Shoshana; Rosen, Clifford J; Iwaniec, Urszula T

    2010-01-01

    Cancellous bone decreases and bone marrow fat content increases with age. Osteoblasts and adipocytes are derived from a common precursor, and growth hormone (GH), a key hormone in integration of energy metabolism, regulates the differentiation and function of both cell lineages. Since an age-related decline in GH is associated with bone loss, we investigated the relationship between GH and bone marrow adiposity in hypophysectomized (HYPOX) rats and in mice with defects in GH signaling. HYPOX dramatically reduced body weight gain, bone growth and mineralizing perimeter, serum insulin-like growth factor 1 (IGF-1) levels, and mRNA levels for IGF-1 in liver and bone. Despite reduced body mass and adipocyte precursor pool size, HYPOX resulted in a dramatic increase in bone lipid levels, as reflected by increased bone marrow adiposity and bone triglyceride and cholesterol content. GH replacement normalized bone marrow adiposity and precursor pool size, as well as mineralizing perimeter in HYPOX rats. In contrast, 17β -estradiol, IGF-1, thyroxine, and cortisone were ineffective. Parathyroid hormone (PTH) reversed the inhibitory effects of HYPOX on mineralizing perimeter but had no effect on adiposity. Finally, bone marrow adiposity was increased in mice deficient in GH and IGF-1 but not in mice deficient in serum IGF-1. Taken together, our findings indicate that the reciprocal changes in bone and fat mass in GH signaling-deficient rodents are not directly coupled with one another. Rather, GH enhances adipocyte as well as osteoblast precursor pool size. However, GH increases osteoblast differentiation while suppressing bone marrow lipid accumulation. © 2010 American Society for Bone and Mineral Research PMID:19821771

  15. Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

    PubMed Central

    Qiu, Wen-Cai; Wang, Zhi-Gang; Wang, Wei-Gang; Yan, Jun; Zheng, Qi

    2008-01-01

    AIM: To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system. PMID:18322959

  16. A STUDY OF SERUM PROLACTIN AND PLASMA HUMAN GROWTH HORMONE IN MALE ALCOHOLICS

    PubMed Central

    Sengupta, Somnath; Ray, Rajat; Desai, Nimesh; Shetty, K. Taranath

    1997-01-01

    Serum levels of prolactin (PRL) and Human Growth Hormone (HGH) were assayed in 38 male alcoholics and 24 male control subjects using radioimmunoassay (RIA) technique. Biochemical parameters of hepatic function and severity of withdrawal state were also assessed. Significantly elevated values of plasma HGH were found in alcoholics as a group. Nineteen percent and eight percent of the patient had elevated serum PRL and HGH levels respectively. Evidence of advanced liver disease was scant and withdrawal symptoms were by and large mild. The findings indicate a dysfunction in hypothalamic adenohypophyseal axis in a subgroup of alcoholics. PMID:21584040

  17. The human growth hormone gene is regulated by a multicomponent locus control region

    SciTech Connect

    Jones, B.; Cooke, N.E.; Liebhaber, S.A.; Monks, B.R.

    1995-12-01

    This article describes research involving the five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene cluster and its expression in the placenta. The results indicate that interactions among multiple elements are required to restrict hGH transcription to the pituitary and generate appropriate levels of expression in the mouse genome. In addition, the results suggest a role for shared and unique regulatory sequences in locus control region-mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the placenta. 67 refs., 9 figs.

  18. Prolactin and growth hormone responses to hypoglycemia in patients with systemic sclerosis and psoriatic arthritis.

    PubMed

    Rovensky, Jozef; Raffayova, Helena; Imrich, Richard; Radikova, Zofia; Penesova, Adela; Macho, Ladislav; Lukac, Jozef; Matucci-Cerinic, Marco; Vigas, Milan

    2006-06-01

    This study compared prolactin (PRL) and growth hormone (GH) responses to hypoglycemia in premenopausal females with systemic sclerosis (SSc) and psoriatic arthritis (PsA) with those in matched healthy controls. No differences were found in glucose and GH responses to hypoglycemia in both groups of patients compared to controls. SSc patients had lower PRL response (P < 0.05) to hypoglycemia compared to controls. PRL response tended to be lower also in PsA patients, however the difference did not reach level of statistical significance (P = 0.11). The present study showed decreased PRL response to hypoglycemia in premenopausal females with SSc. PMID:16855141

  19. Osteosarcoma Associated With Diamond-Blackfan Anaemia: A Case of a Child Receiving Growth Hormone Therapy

    PubMed Central

    Higgs, Deborah; Haddo, Omar; Pringle, Jean

    2004-01-01

    Purpose: Diamond–Blackfan anaemia (DBA) is a rare pure congenital red cell aplasia, usually presenting in infancy or early childhood. The literature suggests a predisposition to haemopoietic malignancy but in addition solid tumours have been reported, with five cases of osteosarcoma described. Patient: A sixth case of a 12-year-old girl with DBA who developed an osteosarcoma of the distal femur is presented. Results: She was treated with methotrexate followed by tumour excision and distal femoral replacement. The patient is currently alive with multiple pulmonary metastases. Discussion: We discuss the association between the administration of growth hormone and future development of malignancy in patients with DBA. PMID:18521394

  20. Experimental Modification of Rat Pituitary Growth Hormone Cell Function During and After Spaceflight

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Salada, T.; Nye, P.; Grossman, E. J.; Lane, P. K.; Grindeland, R. E.

    1996-01-01

    Space-flown rats show a number of flight-induced changes in the structure and function of pituitary Growth Hormone (GH) cells after in vitro postflight testing. To evaluate the possible effects of microgravity on GH cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- 1 micron HydroCortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density less than 1.071 g/sq cm (band 1), cells of density greater than 1.071 g/sq cm (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band I and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

  1. Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to growth hormone (GH) in young animals. The objective of this study was to determine the effect of administration of GH, insulin...

  2. Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects.

    PubMed

    Rollero, A; Murialdo, G; Fonzi, S; Garrone, S; Gianelli, M V; Gazzerro, E; Barreca, A; Polleri, A

    1998-01-01

    Basal growth hormone (GH) and insulin-like growth factor I (IGF-I) as well as GH responses to GH-releasing hormone (GHRH) were studied in 22 subjects (7 females, 15 males), aged between 65 and 86 years. The study was aimed at investigating the possible correlations between the age-dependent GH-IGF-I axis decline and the cognitive function - assessed by the Mini Mental State Examination (MMSE). The relationship between hormonal data, cognition and age, body weight, body mass index (BMI), some nutritional indices (triceps skinfolds, TSF, mid-arm circumference, MAC), and physical activity - quantified by the physical functioning index (PFI)--were also analyzed. GH basal levels were within the normal range, while GH responses to GHRH were blunted in most cases. GH peaks after GHRH were directly correlated with GH basal values. IGF-I serum levels were found to be in the lower part of the reference range for adult subjects or below it. GH responses to GHRH, but not GH and IGF-I basal levels, were inversely correlated with subject age. GH secretion areas after GHRH were inversely correlated with BMI, but no further correlations between GH data and clinical or nutritional parameters were found. MMSE values directly correlated with MAC and PFI values. IGF-I levels were directly correlated with MMSE scores, being lowered in patients with more advanced cognitive deterioration, and with MAC values--the decrease of which is thought to reflect protein caloric malnutrition--but not with body weight, BMI, TSF and PFI. MMSE-related protein caloric malnutrition and decreased physical activity possibly take part in affecting IGF- I function in subjects with mild cognitive impairment and, reciprocally, IGF-I decrement might affect neuronal function. PMID:9732206

  3. 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.

  4. Elongation growth of the leaf sheath base of Avena sativa seedlings: regulation by hormones and sucrose

    NASA Technical Reports Server (NTRS)

    Brock, T. G.; Kaufman, P. B.

    1991-01-01

    The leaf sheath base of the seedling of Avena sativa was characterized for growth response to hormones and sucrose. Six day old plants, raised under a 10:14 hr light:dark cycle, were excised at the coleoptilar node and 1 cm above the node for treatment. The growth of the leaf sheath base was promoted by gibberellic acid (GA3) and this response was dose dependent. The lag to response initiation was approximately 4 hr. Growth with or without GA3 (10 micromoles) was transient, diminishing appreciably after 48 hr. The addition of 10 mM sucrose greatly prolonged growth; the effect of GA3 and sucrose was additive. Neither indole-3-acetic acid (IAA) nor the cytokinin N6-benzyladenine (BA), alone or in combination, promoted the growth of leaf sheath bases. However, both significantly inhibited the action of GA3. The inhibitory effect of IAA was dose dependent and was not affected by the addition of BA or sucrose. These results indicate that the growth of leaf sheath bases of Avena sativa is promoted specifically by gibberellin, that this action depends on the availability of carbohydrates from outside of the leaf sheath base, and that the promotional effect of GA3 can be modified by either auxins or cytokinins.

  5. Divergent selection for shape of growth curve in Japanese quail. 4. Carcase composition and thyroid hormones.

    PubMed

    Hyánková, L; Novotná, B; Darras, V M

    2008-03-01

    1. Changes in the relative weights of carcase, abdominal fat, breast and leg muscles, and plasma thyroid hormone concentrations occurring during the first 6 weeks of postnatal growth were analysed in males of HG and LG lines divergently selected for high and low relative body weight (BW) gain between 11 and 28 d of age, respectively, and constant adult BW. 2. The second week of postnatal life was a critical age at which the HG males exhibited a relatively faster growth in comparison to their LG counterparts and permanently exceeded LG males in the percentage by weight of carcase, breast and leg muscle. A higher production of muscle tissues was associated with lower accumulation of abdominal fat before sexual maturity. 3. In general, the plasma T(3) level of HG quail exceeded that of LG quail. Nevertheless, significant differences were found only at 14, 21 and 28 d of age, that is, in the period during which the highest inter-line differences in relative growth rate were noted. Also the T(3)/T(4) ratio followed a similar trend while plasma T(4) level showed no clear and consistent inter-line differences. 4. The results suggest that the selection for the shape of the growth curve, like the selection for body fat, modifies the carcase quality owing to shortening/prolongation of the acceleration growth phase. Individuals with a short acceleration phase of the growth curve are characterised by low carcase quality during the fattening period. PMID:18409082

  6. 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

  7. Co-induction of hepatic IGF-I and progranulin mRNA by growth hormone in tilapia, Oreochromis mossambiccus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Like IGF-I, progranulin (pgrn) is a growth factor involved in tumorigenesis and wound healing. We report here the identification and characterization of pgrn cDNA in tilapia and the regulation of its expression by growth hormone(GH). The tilapia pgrn cDNA was cloned by RT-PCR ampliWcation, using g...

  8. Effects of short term growth hormone treatment on the rainbow trout (Oncorhynchus mykiss) liver and muscle transcriptomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous studies have established that recombinant bovine Somatotropin (rbST, aka bovine growth hormone) stimulates growth in the rainbow trout. However, the effects of rbST on target tissue gene expression are not well characterized. In the current study, we used Posilac® (Monsanto Co., St. Louis, ...

  9. Effect of feed deprivation and insulin-like growth hormone on indices of protein degradation in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin-like growth factor-I (IGF-I) is a hormone that promotes growth by both increasing protein synthesis and decreasing protein degradation. This study utilizes a comparative slaughter approach to determine the effect of feed deprivation and IGF-I treatment on weight loss and indices of protein ...

  10. 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

  11. Effects of inorganic iodide, epidermal growth factor and phorbol ester on hormone synthesis by porcine thyroid follicles cultured in suspension

    SciTech Connect

    Kasai, Kikuo; Ichimura, Kenichi; Banba, Nobuyuki; Emoto, Tatsushi; Hiraiwa, Masaki; Hishinuma, Akira; Hattori, Yoshiyuki; Shimoda, Shinichi ); Yamaguchi, Fumihiko; Hosoya, Toichiro )

    1992-01-01

    Porcine thyroid follicles cultured in suspension for 96 h synthesized and secreted thyroid hormones in the presence of thyrotropin (TSH). The secretion of newly synthesized hormones was assessed by determining in the contents of thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) in the media and by paperchromatographic analysis of {sup 125}I-labeled hormones in the media where the follicles were cultured in the presence and absence of inhibitors of hormone synthesis. The hormone synthesis and secretion was modified by exogenously added NaI. The maximal response was obtained at 1 {mu}M. Thyroid peroxidase (TPO) activity in the cultured follicles with TSH for 96 h was dose-dependently inhibited by NaI. One hundred {mu}M and NaI completely inhibited TSH-induced TPO activity. Moreover, both epidermal growth factor and phorbol 12-myristate 13-acetate inhibited de novo hormone synthesis. An induction of TPO activity by TSH was also inhibited by either agent. These data provide direct evidences that thyroid hormone synthesis is regulated by NaI as well as TSH at least in part via regulation of TPO activity and also that both EGF and PMA are inhibitory on thyroid hormone formation.

  12. Role of obestatin on growth hormone secretion: An in vitro approach

    SciTech Connect

    Pazos, Yolanda; Alvarez, Carlos J.P.; Camina, Jesus P.; Al-Massadi, Omar; Seoane, Luisa M.; Casanueva, Felipe F.

    2009-12-25

    Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of G{sub i}, PI3k, novel PKC{epsilon}, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30 min, being more acute at 15 min. At 1 h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on the capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.

  13. Expression of the gene encoding growth hormone in the human mammary gland

    SciTech Connect

    Mol, J.A.; Misdorp, W.; Rijnberk, A.

    1995-10-01

    Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer. 21 refs., 2 figs., 1 tab.

  14. Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth

    NASA Technical Reports Server (NTRS)

    Barth, Jacques D.; Jansen, Hans; Reiber, Johan H. C.; Birkenhager, Jan C.; Kromhout, Daan

    1987-01-01

    The relationships between the coronary lesion growth and the blood contents of lipoprotein fractions, thyroic hormones, and the lipoprotein lipase activity were investigated in male patients with severe coronary atherosclerosis, who participated in a lipid-lowering dietary intervention program. A quantitative computer-assisted image-processing technique was used to assess the severity of coronary obstructions at the beginning of the program and at its termination two years later. Based on absolute coronary scores, patients were divided into a no-lesion growth group (14 patients) and a progression group (21 paients). At the end of the trial, the very-low-density lipoprotein cholesterol and triglycerides were found to be significantly higher, while the high-density lipoprotein cholesterol and hepatic lipase (HL) were lower in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions.

  15. A chemiluminescent metalloimmunoassay based on copper-enhanced gold nanoparticles for quantification of human growth hormone.

    PubMed

    Hasanpour, Foroozan; Khayamian, Taghi; Ensafi, Ali A; Rahmani, Hamidreza; Rezaei, Behzad

    2013-01-01

    A chemiluminescence (CL) immunoassay was developed to determine human growth hormone (hGH) based on copper-enhanced gold nanoparticles. In this method, gold nanoparticles were deposited on polystyrene wells for adsorption of human growth antibodies as well as catalyst for reducing of copper ions from the copper enhancer solution. The reduction of copper ions was prevented where the gold nanoparticles were covered by the antibody-antigen immunocomplex. The deposited copper on Au nanoparticles was then dissolved in HNO3 solution and quantified using the CL method. The CL intensity response was logarithmically dependent on the hGH concentrations over the range 0.2-50 ng/mL, with a detection limit (3σ) of 0.036 ng/mL. PMID:23008231

  16. Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

    PubMed Central

    Martín-Rodríguez, Juan F.; Muñoz-Bravo, Jose L.; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M.; Castaño, Justo P.; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A.

    2015-01-01

    Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors. PMID:26549306

  17. Acceleration of puberty during growth hormone therapy in a child with septo-optic dysplasia.

    PubMed

    Catlı, Gönül; Altıncık, Ayça; Anık, Ahmet; Demir, Korcan; Güleryüz, Handan; Abacı, Ayhan; Böber, Ece

    2014-01-01

    Septo-optic dysplasia (SOD) is a heterogeneous disorder of the central nervous system characterized by various endocrinological and neurological findings. It is a complex disease caused by a combination of genetic and environmental factors. Herein, we report the case of a 5.5-year-old girl who presented with short stature and strabismus. Ophthalmological examination revealed bilateral optic nerve hypoplasia. Ectopic posterior pituitary and bilateral optic hypoplasia were detected on brain magnetic resonance imaging. The presence of bilateral optic nerve hypoplasia and hypopituitarism led to the diagnosis of SOD. An abated growth hormone (GH) response was found in the GH stimulation test and GH replacement therapy was initiated. At the end of the first year of clinical follow-up, secondary hypothyroidism was detected and L-thyroxine was added to the treatment. At the age of 8.25 years, thelarche was noted and 6 months later, the patient presented with menarche. At this time, the bone age was 12 years and the basal luteinizing hormone level was 7 mIU/mL. These findings indicated acceleration in the process of pubertal development. We report this case (i) to emphasize the need to investigate hypopituitarism in cases with bilateral optic nerve hypoplasia and (ii) to draw attention to the fact that during the follow-up of SOD cases receiving GH therapy, inappropriate acceleration of growth velocity and rapid improvement in bone age may be predictive of central precocious puberty development. PMID:24932606

  18. Growth hormone secretagogue receptor deficiency in mice protects against obesity‐induced hypertension

    PubMed Central

    Harris, Louise E.; Morgan, David G.; Balthasar, Nina

    2014-01-01

    Abstract Growth hormone secretagogue receptor (GHS‐R) signaling has been associated with growth hormone release, increases in food intake and pleiotropic cardiovascular effects. Recent data demonstrated that acute GHS‐R antagonism leads to increases in mean arterial pressure mediated by the sympathetic nervous system in rats; a highly undesirable effect if GHS‐R antagonism was to be used as a therapeutic approach to reducing food intake in an already obese, hypertensive patient population. However, our data in conscious, freely moving GHS‐R deficient mice demonstrate that chronic absence of GHS‐R signaling is protective against obesity‐induced hypertension. GHS‐R deficiency leads to reduced systolic blood pressure variability (SBPV); in response to acute high‐fat diet (HFD)‐feeding, increases in the sympathetic control of SBPV are suppressed in GHS‐R KO mice. Our data further suggest that GHS‐R signaling dampens the immediate HFD‐mediated increase in spontaneous baroreflex sensitivity. In diet‐induced obesity, absence of GHS‐R signaling leads to reductions in obesity‐mediated hypertension and tachycardia. Collectively, our findings thus suggest that chronic blockade of GHS‐R signaling may not result in adverse cardiovascular effects in obesity. PMID:24760503

  19. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  20. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury.

    PubMed

    Kreber, Lisa A; Griesbach, Grace S; Ashley, Mark J

    2016-09-01

    This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  1. Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation

    PubMed Central

    Devesa, Jesús; Lema, Hortensia; Zas, Eva; Munín, Borja; Taboada, Pilar; Devesa, Pablo

    2016-01-01

    Background—To describe the results obtained after treating a non growth hormone-deficient 10-year-old girl who suffered asphyxia during delivery, resulting in important cognitive deficits, with growth hormone (GH) and neurorehabilitation. Methods—GH was administered (mg/day) at doses of 0.5 over three months followed by 0.9, every two weeks over three months, and then alternating 1.2 three days/week and 0.3 two days/week. Neurorehabilitation consisted of daily sessions of neurostimulation, speech therapy, occupational therapy and auditive stimulation. Treatment lasted nine months. Results—Scores obtained in all the areas treated showed that, at discharge, the patient clearly increased her cognitive abilities, memory and language competence index; her intelligence quotient score increased from 51 to 80, and the index of functional independence measure reached a value of 120 over 126 (maximal value). Conclusions—This case suggests that GH administration may play a role in improving cognitive deficits during neurorehabilitation in children with brain damage suffered during delivery. This agrees with the known effects of GH on cognition. PMID:26821051

  2. Molecular genetic analysis of X-linked hypogammaglobulinemia and isolated growth hormone deficiency

    SciTech Connect

    Stewart, D.M.; Kurman, C.C.; Staudt, L.M.

    1995-09-01

    In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton`s X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton`s tyrosine kinase gene (BTK) are responsible for Bruton`s XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton`s XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome. 17 refs., 4 figs.

  3. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

    PubMed Central

    Griesbach, Grace S.; Ashley, Mark J.

    2016-01-01

    Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  4. Growth hormone protects human lymphocytes from irradiation-induced cell death

    PubMed Central

    Lempereur, Laurence; Brambilla, Daria; Maria Scoto, Giovanna; D'Alcamo, Maria; Goffin, Vincent; Crosta, Lucia; Palmucci, Tullio; Rampello, Liborio; Bernardini, Renato; Cantarella, Giuseppina

    2003-01-01

    Undesired effects of cancer radiotherapy mainly affect the hematopoietic system. Growth hormone (GH) participates in both hematopoiesis and modulation of the immune response. We report both r-hGH cell death prevention and restoration of secretory capacities of irradiated human peripheral blood lymphocytes (PBL) in vitro. r-hGH induced cell survival and increased proliferation of irradiated cells. Western blot analysis indicated that these effects of GH were paralleled by increased expression of the antiapoptotic protein Bcl-2. r-hGH restored mitogen-stimulated release of IL-2 by PBL. Preincubation of irradiated lymphocytes with the growth hormone receptor (GHR) antagonists B2036 and G120 K abrogated r-hGH-dependent IL-2 release. These results demonstrate that r-hGH protects irradiated PBL from death in a specific, receptor-mediated manner. Such effect of r-hGH on PBL involves activation of the antiapoptotic gene bcl-2 and prevention of cell death, associated with preserved functional cell capacity. Finally, potential use of GH as an immunopotentiating agent could be envisioned during radiation therapy of cancer. PMID:12721095

  5. A Mathematical Model of Prostate Tumor Growth Under Hormone Therapy with Mutation Inhibitor

    NASA Astrophysics Data System (ADS)

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2010-04-01

    This paper extends Jackson’s model describing the growth of a prostate tumor with hormone therapy to a new one with hypothetical mutation inhibitors. The new model not only considers the mutation by which androgen-dependent (AD) tumor cells mutate into androgen-independent (AI) ones but also introduces inhibition which is assumed to change the mutation rate. The tumor consists of two types of cells (AD and AI) whose proliferation and apoptosis rates are functions of androgen concentration. The mathematical model represents a free-boundary problem for a nonlinear system of parabolic equations, which describe the evolution of the populations of the above two types of tumor cells. The tumor surface is a free boundary, whose velocity is equal to the cell’s velocity there. Global existence and uniqueness of solutions of this model is proved. Furthermore, explicit formulae of tumor volume at any time t are found in androgen-deprived environment under the assumption of radial symmetry, and therefore the dynamics of tumor growth under androgen-deprived therapy could be predicted by these formulae. Qualitative analysis and numerical simulation show that controlling the mutation may improve the effect of hormone therapy or delay a tumor relapse.

  6. Issues and trends in pediatric growth hormone therapy--an update from the GHMonitor observational registry.

    PubMed

    Pitukcheewanont, Pisit; Desrosiers, Paul; Steelman, Joel; Rapaport, Robert; Fuqua, John S; Kreher, Nerissa C; Hamlett, Anthony

    2008-02-01

    The GHMonitor observational registry collates data on pediatric subjects receiving Saizen (recombinant human growth hormone (GH)) therapy. From January 2003 through August 2006, 1335 subjects were enrolled in the registry, approximately two-thirds of whom are male. The most common diagnosis in the registry is idiopathic growth hormone deficiency (58%). Most subjects in GHMonitor are receiving Saizen doses using a needle-free delivery device, the cool.click (73%). Mean height standard deviation scores show an improvement from -2.1 at screening to -1.1 following 3 years of Saizen therapy. To date, adverse events have been reported in 4% of subjects. Three serious adverse events were identified to be related to Saizen by the primary investigator: cellulitis at the injection site, behavioral problems/suicidal ideation, and enlargement of a craniopharyngioma. This article provides an update on data from the registry and briefly discusses topical and controversial issues in the treatment of pediatric patients requiring GH therapy. PMID:18317441

  7. Human growth hormone: new delivery systems, alternative routes of administration, and their pharmacological relevance.

    PubMed

    Cázares-Delgadillo, J; Ganem-Rondero, A; Kalia, Y N

    2011-06-01

    The availability of recombinant human growth hormone (GH) has broadened its range of clinical applications. Approved indications for GH therapy include treatment of growth hormone deficiency (in children and in adults), Turner syndrome, Prader-Willi syndrome, chronic renal insufficiency and more recently, idiopathic short stature in children, AIDS-related wasting and fat accumulation associated with lipodystrophy in adults. Therapy with GH usually begins at a low dose and is gradually titrated to obtain optimal efficacy while minimizing side effects. It is usually administered on a daily basis by subcutaneous injection, since this was considered to impact upon patient compliance, extended-release GH preparations were developed and new delivery platforms - e.g., auto-injectors and needle-free devices - were introduced in order to improve not only compliance and convenience but also dosing accuracy. In addition, alternative less invasive modes of administration such as the nasal, pulmonary and transdermal routes have also been investigated. Here, we provide an overview of the different technologies and routes of GH administration and discuss the principles, limitations and pharmacological profiles for each approach. PMID:21296662

  8. 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.

  9. Cytokine inhibition of JAK-STAT signaling: a new mechanism of growth hormone resistance.

    PubMed

    Lang, Charles H; Hong-Brown, Ly; Frost, Robert A

    2005-03-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-I are potent regulators of muscle mass in health and disease. This somatomedin axis is markedly deranged in various catabolic conditions in which circulating and tissue levels of inflammatory cytokines are elevated. The plasma concentration of IGF-I, which is primarily determined by hepatic synthesis and secretion of the peptide hormone, is dramatically decreased during catabolic and inflammatory conditions. Moreover, many of these conditions are also associated with an inability of GH to stimulate hepatic IGF-I synthesis. This defect results from an impaired phosphorylation and activation of the traditional JAK2/STAT5 signal transduction pathway. Numerous lines of evidence support the role of tumor necrosis factor (TNF)-alpha as a prominent but probably not the sole mediator of the sepsis-induced impairment in basal and GH-stimulated IGF-I synthesis in liver. Additionally, catabolic conditions produce comparable alterations in skeletal muscle. However, in contrast to liver, the GH resistance in muscle is not mediated by a defect in STAT5 phosphorylation. Muscle is now recognized to respond to infectious stimuli with the production of numerous inflammatory cytokines, including TNF-alpha. Furthermore, myocytes cultured with TNF-alpha are GH resistant and this defect appears mediated via a STAT5-independent but JNK-dependent mechanism. Collectively, these changes act to limit IGF-I availability in muscle, which disturbs protein balance and results in the loss of protein stores in catabolic and inflammatory conditions. PMID:15549417

  10. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH. PMID:26169108

  11. Quantification of insulin-like growth factor-1 in dried blood spots for detection of growth hormone abuse in sport.

    PubMed

    Cox, Holly D; Rampton, Jessica; Eichner, Daniel

    2013-02-01

    There is significant evidence that athletes are using recombinant human growth hormone (rhGH) to enhance performance, and its use is banned by the World Anti-Doping Agency and professional sports leagues. Insulin-like growth factor-1 (IGF-1) is the primary mediator of growth hormone action and is used as a biomarker for the detection of rhGH abuse. The current biomarker-based method requires collection and expedited shipment of venous blood which is costly and may decrease the number of tests performed. Measurement of GH biomarkers in dried blood spots (DBS) would considerably simplify sample collection and shipping methods to allow testing of a greater number of samples regardless of location. A method was developed to quantify intact IGF-1 protein in DBS by liquid chromatography-tandem mass spectrometry. A step-wise acid-acetonitrile extraction was optimized to achieve a sensitive assay with a lower limit of quantification of 50 ng/mL. IGF-1 remained stable at room temperature for up to 8 days, which would allow shipment of DBS cards at ambient temperature. In a comparison between plasma concentrations of IGF-1 and concentrations measured from venous and finger prick DBS, there was good correlation and agreement, r(2) of 0.8551 and accuracy of 86-113 % for venous DBS and r(2) of 0.9586 and accuracy of 89-122 % for finger prick DBS. The method is intended for use as a rapid screening method for IGF-1 to be used in the biomarker method of rhGH abuse detection. PMID:23263515

  12. 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

  13. Effects of growth hormone therapeutic supplementation on hematopoietic stem/progenitor cells in children with growth hormone deficiency: focus on proliferation and differentiation capabilities.

    PubMed

    Kawa, M P; Stecewicz, I; Piecyk, K; Pius-Sadowska, E; Paczkowska, E; Rogińska, D; Sobuś, A; Łuczkowska, K; Gawrych, E; Petriczko, E; Walczak, M; Machaliński, B

    2015-09-01

    We investigated the direct effects of growth hormone (GH) replacement therapy (GH-RT) on hematopoiesis in children with GH deficiency (GHD) with the special emphasis on proliferation and cell cycle regulation. Peripheral blood (PB) was collected from sixty control individuals and forty GHD children before GH-RT and in 3rd and 6th month of GH-RT to measure hematological parameters and isolate CD34(+)-enriched hematopoietic progenitor cells (HPCs). Selected parameters of PB were analyzed by hematological analyzer. Moreover, collected HPCs were used to analyze GH receptor (GHR) and IGF1 expression, clonogenicity, and cell cycle activity. Finally, global gene expression profile of collected HPCs was analyzed using genome-wide RNA microarrays. GHD resulted in a decrease in several hematological parameters related to RBCs and significantly diminished clonogenicity of erythroid progenies. In contrast, GH-RT stimulated increases in clonogenic growth of erythroid lineage and RBC counts as well as significant up-regulation of cell cycle-propagating genes, including MAP2K1, cyclins D1/E1, PCNA, and IGF1. Likewise, GH-RT significantly modified GHR expression in isolated HPCs and augmented systemic IGF1 levels. Global gene expression analysis revealed significantly higher expression of genes associated with cell cycle, proliferation, and differentiation in HPCs from GH-treated subjects. (i) GH-RT significantly augments cell cycle progression in HPCs and increases clonogenicity of erythroid progenitors; (ii) GHR expression in HPCs is modulated by GH status; (iii) molecular mechanisms by which GH influences hematopoiesis might provide a basis for designing therapeutic interventions for hematological complications related to GHD. PMID:25920498

  14. Differential effects of STAT proteins on growth hormone-mediated IGF-I gene expression.

    PubMed

    Varco-Merth, Ben; Rotwein, Peter

    2014-11-01

    Growth hormone (GH) plays a key role regulating somatic growth and in controlling metabolism and other physiological processes in humans and other animal species. GH acts by binding to the extracellular part of its transmembrane receptor, leading to induction of multiple intracellular signal transduction pathways that culminate in changes in gene and protein expression. A key agent in GH-stimulated growth is the latent transcription factor signal transducer and activator of transcription (STAT) 5B, one of four STAT proteins induced by the GH receptor in cultured cells and in vivo. As shown by genetic and biochemical studies, GH-activated STAT5B promotes transcription of the gene encoding the critical growth peptide, insulin-like growth factor-I (IGF-I), and natural null mutations of STAT5B in humans lead to growth failure accompanied by diminished IGF-I expression. Here we have examined the possibility that other GH-activated STATs can enhance IGF-I gene transcription, and thus potentially contribute to GH-regulated somatic growth. We find that human STAT5A is nearly identical to STAT5B in its biochemical and functional responses to GH but that STAT1 and STAT3 show a weaker profile of in vitro binding to STAT DNA elements from the IGF-I gene than STAT5B, and are less potent inducers of gene transcription through these elements. Taken together, our results offer a molecular explanation for why STAT5B is a key in vivo mediator of GH-activated IGF-I gene transcription and thus of GH-regulated somatic growth. PMID:25205818

  15. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    PubMed

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. PMID:26943480

  16. Somatic growth effects of intramuscular injection of growth hormone in androgen-treated juvenile Nile tilapia, Oreochromis niloticus (Perciformes: Cichlidae).

    PubMed

    Liñán-Cabello, Marco A; Robles-Basto, Cindy M; Mena-herrera, Alfredo

    2013-03-01

    Little is known about the effects of the interaction of growth hormone (GH) with 17 alpha-methyltestosterone (17-MT) during fish growth. We evaluated this in the present study to assess the effect on fish growth. Fish in two batches of juvenile tilapia (Oreochromis niloticus) (approximately 5.0cm in length) were randomly assigned in triplicate to three treatments and a control group, distributed among 12 fiberglass tanks of 1 000L capacity (50 fish per tank) in an experiment covering a period of six weeks. The experimental groups were: a) fish treated with 17-MT and GH in mineral oil (RGH); b) fish treated with 17-MT and mineral oil without the addition of GH (R); c) fish treated with GH in mineral oil but not 17-MT (NGH); and d) fish of the control group, which were treated with mineral oil but not 17-MT or GH (N). The GH was injected into the fish at a rate of 0.625mg/g body weight. Morphometric data were recorded at the beginning of the experiment (T0) and at 15, 30 and 45 days (T15, T30 and T45), and various indicators of growth were assessed: condition factor (K); survival percentage (S), feed conversion rate (FCR), percentage weight gain (WG) and (v) daily weight gain. The optimum dietary level was calculated assuming 5% food conversion to total weight in each group. During the experiment, the fish were provided with a commercial food containing 45% protein. The data showed that GH injection resulted in a greater weight gain in fish treated with 17-MT (the RGH treatment group), being particularly significant increase in weight during T15 and T30 (p<0.05). High values of K were found in the R and RGH treatments during the initial days of the experiment, which may have been a consequence of the better nutritional status affecting both weight gain and growth in body length, as a result of the additive effects of 17-MT and GH. The fish in groups not treated with 17-MT and treated with 17-MT and added GH showed greater increases in WG per day, higher K values and

  17. 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.

  18. 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.

  19. Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli.

    PubMed

    Chan, Chi-Bun; Cheng, Christopher H K

    2004-02-12

    Two cDNA transcripts, namely sbGHSR-1a and sbGHSR-1b, for growth hormone secretagogue receptor (GHSR), were identified from the seabream pituitary. When translated, the sbGHSR-1a encodes for a protein of 385 amino acids (aa) with seven putative transmembrane domains and the sbGHSR-1b contains 295 aa with five putative transmembrane domains. Tissue distribution studies indicated that the two receptors are mainly expressed in the central nervous system of the fish. The sbGHSR-1a transcript has the highest expression level in the pituitary. The sbGHSR-1b transcript, on the other hand, has the highest expression level in the telencephalon. Genomic Southern analysis indicated that there is a single gene for GHSR in the seabream genome. Comparison of the cDNA sequences of sbGHSR1a and sbGHSR1b with the seabream genomic sequence indicated that the presence of the two receptor transcripts is a result of alternative splicing of the single GHSR gene. The two receptor cDNAs were expressed in cultured eukaryotic cells for functional analyses. A variety of structurally diverse growth hormone secretogogues (GHS), including the peptide GHS (GHRP-6 and ghrelin), the benzolactam GHS (L692,585) and the spiropiperidine GHS (L163,255), were able to trigger an elevation of intracellular Ca(2+) ion concentration in HEK293 cells expressing sbGHSR-1a, but not in cells expressing sbGHSR-1b. Microphysiometry revealed that an increase in extracellular acidification rate (EAR) could be detected in CHO cells expressing the sbGHSR-1a receptor when stimulated with GHRP-6. On the contrary, CHO cells expressing the sbGHSR-1b receptor registered no detectable EAR changes. However, when sbGHSR-1b was co-expressed with sbGHSR-1a in HEK293 cells, the signal transduction capacity of sbGHSR-1a was attenuated. This is the first report on the identification of a GHSR-1b transcript from species other than mammals and the demonstration that receptor interaction might provide a possible explanation for the

  20. Should Patients with Trichorhinophalangeal Syndrome be Tested for Growth Hormone Deficiency?

    PubMed

    Marques, Jorge Sales; Maia, Catarina; Almeida, Raquel; Isidoro, Lara; Dias, Catarina

    2015-09-01

    Type 1 Trichorhinophalangeal syndrome (TRPS) is characterized by typical facial and skeletal abnormalities. These patients frequently exhibit short stature; however, only one case with growth hormone (GH) deficiency can be found in the literature. Our patient is a 10-year-old girl with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity: c. 1198C>T (p. Gln400X) and c.2086C>T (p. Arg696X). She has an additional GH deficiency. The patient is short in stature, with a growth velocity of 1.5 cm per year (SDS - 4.07), a bone age of 4.5 years, and she shows no response to the GH stimulation tests. According to a previous report of an identical case, catch-up growth will occur after beginning GH treatment. We believe that GH stimulation tests should be performed on patients with TRPS1 exhibiting a growth velocity below the normal range expected for their age and sex. If the result is subnormal, then GH therapy should be attempted. PMID:26540763

  1. Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice.

    PubMed Central

    Shanahan, C M; Rigby, N W; Murray, J D; Marshall, J T; Townrow, C A; Nancarrow, C D; Ward, K A

    1989-01-01

    Transgenic mice containing a sheep metallothionein 1a-sheep growth hormone fusion gene exhibited low, tissue-specific basal levels of transgene mRNA expression, resulting in slightly elevated levels of circulating growth hormone that did not lead to a detectable increase in growth. After zinc stimulation, high levels of transgene mRNA expression were induced in a number of tissues; these levels correlated with increased levels of circulating growth hormone, resulting in growth increases of up to 1.5 times the levels of controls and unstimulated transgenic mice. After removal of the zinc stimulus, transgene expression and circulating growth hormone concentrations returned to basal levels. Additional evidence from the pattern of developmental expression of the transgene suggests that zinc is the main regulator of this promoter in mice. The demonstrated regulation and low basal level of expression of the sheep metallothionein 1a promoter make it a candidate for use in other mouse transgenic studies and for use in transgenic livestock, in which regulation of expression is essential. Images PMID:2479830

  2. Expression of IGF-I and Protein Degradation Markers During Hindlimb Unloading and Growth Hormone Administration in Rats

    NASA Astrophysics Data System (ADS)

    Leinsoo, T. A.; Turtikova, O. V.; Shenkman, B. S.

    2013-02-01

    It is known that hindlimb unloading or spaceflight produce atrophy and a number of phenotypic alterations in skeletal muscles. Many of these processes are triggered by the axis growth hormone/insulin-like growth factor I. However growth hormone (GH) and insulin-like growth factor I (IGF-I) expression relationship in rodent models of gravitational unloading is weakly investigated. We supposed the IGF-I is involved in regulation of protein turnover. In this study we examined the IGF-I expression by RT-PCR assay in the rat soleus, tibialis anterior and liver after 3 day of hindlimb suspension with growth hormone administration. Simultaneously were studied expression levels of MuRF-1 and MAFbx/atrogin as a key markers of intracellular proteolysis. We demonstrated that GH administration did not prevent IGF-I expression decreasing under the conditions of simulated weightlessness. It was concluded there are separate mechanisms of action of GH and IGF-I on protein metabolism in skeletal muscles. Gravitational unloading activate proteolysis independently of growth hormone activity.

  3. Impaired growth hormone secretion in neonatal hypothyroid rats: hypothalamic versus pituitary component.

    PubMed

    De Gennaro, V; Cella, S G; Bassetti, M; Rizzi, R; Cocchi, D; Muller, E E

    1988-01-01

    In 10-day-old rats made hypothyroid by giving dams propylthiouracil (PTU) in the drinking water since the day of parturition, simultaneous radioimmunoassay (RIA) determinations of basal and stimulated growth hormone (GH) secretion, hypothalamic GH-releasing hormone (GHRH)-like immunoreactivity (LI) content, immunocytochemical localization of somatotrophs, and hypothalamic GHRH-LI-positive structures were performed. The frequency of somatotrophs was also determined. One-day-old hypothyroid rats, whose mothers had been given PTU since the 14th day of pregnancy, were also used for comparison. In 10-day-old hypothyroid rats, pituitary and plasma GH levels and the number of somatotrophs were considerably lower and plasma TSH levels were significantly higher than those in age-matched control rats; however, GHRH-LI titers in the mediobasal hypothalamus and the morphology of GHRH-LI-positive structures were unaltered. In 1-day-old rats the only alteration present, in addition to elevated plasma TSH levels, was a clear-cut decrease in plasma GH levels. An acute challenge with GHRH (20 ng/100 g body wt, sc) or clonidine (15 micrograms/100 g body wt, sc) induced a clear-cut rise in plasma GH levels 15 min postinjection in 10-day-old control rats but failed to do so in age-matched hypothyroid rats. Both compounds failed to rise plasma GH in both hypothyroid and control 1-day-old rats. Taken together these data indicate that in neonatal and infant rats deprivation of thyroid hormones acts primarily to depress pituitary somatotroph function and that possible changes in GHRH-secreting structures represent a later postnatal event. PMID:3124121

  4. Growth hormone in vascular pathology: neovascularization and expression of receptors is associated with cellular proliferation.

    PubMed

    Lincoln, D T; Singal, P K; Al-Banaw, A

    2007-01-01

    Vascular tumours are common lesions of the skin and subcutaneous tissue, but also occur in many other tissues and internal organs. The well-differentiated tumours consist of irregular anastomosing, blood-filled vascular channels that are lined by variably atypical endothelial cells. The less differentiated tumours may show solid strands and sheets, resembling carcinoma or lymphoma. Several growth factors, including basic fibroblast growth factor, transforming growth factors and vascular endothelial growth factor, play a role in tumour angiogenesis. Growth hormone (GH) is mitogenic for a variety of vascular tissue cells, including smooth muscle cells, fibroblasts and endothelial cells and exerts its regulatory functions in controlling metabolism, balanced growth and differentiated cell expression by acting on specific membrane-bound receptors, which trigger a phosphorylation cascade resulting in the modulation of numerous signalling pathways and of gene expression. Essential to the initiation of a cellular response to GH, the presence of receptors for this hormone may predict the adaptation of tumour cells resulting from GH exposure. To address the site/mode of action through which GH exerts its effects, a well characterized monoclonal antibody, obtained by hybridoma technology from Balb/c mice immunized with purified rabbit and rat liver GH-receptor (GHR) and directed against the hormone binding site of the receptor, was applied, using the ABC technique to determine GHR expression in a panel of vascular tumours. The GHR was cloned from a rabbit liver cDNA library with the aid of an oligonucleotide probe based on a 19 residue tryptic peptide sequence derived from 5900 fold purified rabbit liver receptor. A total of 64 benign and malignant vascular tumours were obtained from different human organ sites, including the chest wall, skin, axillary contents, duodenum, female breast, abdomen, stomach, colon, lymph node, bladder, body flank and neck regions. The tumours

  5. Growth hormone enhances amino acid uptake by the human small intestine.

    PubMed Central

    Inoue, Y; Copeland, E M; Souba, W W

    1994-01-01

    OBJECTIVE: The effects of growth hormone (GH) on the luminal transport of amino acids and glucose by the human small intestine were investigated. SUMMARY BACKGROUND DATA: The anabolic effect of growth hormone administration is associated with nitrogen retention and an increase muscle strength, but the impact of growth hormone on nutrient uptake from the gut lumen has not been examined. METHODS: Twelve healthy patients received a daily subcutaneous dose of low-dose GH (0.1 mg/kg), high-dose GH (0.2 mg/kg), or no treatment (controls) for 3 days before surgery. At operation, ileum (8 patients) or jejunum (4 patients) was resected, and brush border membrane vesicles (BBMVs) were prepared by differential centrifugation. Vesicle purity was confirmed by a 16-fold enrichment of marker enzymes. The carrier-mediated transport of glutamine (System B), leucine (System L), alanine (System B), arginine (System y+), MeAIB (methyl alpha-aminoisobutyric acid [System A]), and glucose (Na(+)-dependent glucose transporter) by BBMVs was measured by a rapid mixing/filtration technique. RESULTS: Treatment with low-dose GH resulted in a statistically insignificant increase in amino acid transport rates in jejunal and ileal BBMVs. High-dose GH resulted in a generalized 20%-to 70%-stimulation of amino acid transport, whereas glucose transport was not affected. The effects of GH were similar in ileum and jejunum. Kinetic analysis of the transport of glutamine (the most abundant amino acid in the body and the principal gut fuel) and the essential amino acid leucine revealed that the increase in transport was caused by a 50% increase in carrier Vmax, consistent with an increase in the number of functional carriers in the brush border membrane. Pooled analysis of transport velocities demonstrated that total rates of amino acid uptake from the gut lumen were increased significantly by 35% in GH-treated patients. CONCLUSIONS: The ability of GH to enhance amino acid uptake from the gut lumen

  6. Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells

    PubMed Central

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-01-01

    Summary Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development. PMID:24936466

  7. Prospective study of the development of growth hormone deficiency in children given cranial irradiation, and its relation to statural growth

    SciTech Connect

    Brauner, R.; Rappaport, R.; Prevot, C.; Czernichow, P.; Zucker, J.M.; Bataini, P.; Lemerle, J.; Sarrazin, D.; Guyda, H.J.

    1989-02-01

    Although GH deficiency (GHD) is the most frequent hormonal abnormality that occurs after cranial radiation, the natural course of this complication and its relationship to growth in children are not known. Therefore, we undertook a 2-yr prospective study of 16 children, aged 1.7-15 yr at the time of treatment, who received cranial (31-42 Gy (1 Gy = 100 rads)) and spinal radiation for medulloblastoma or ependymoma (group I). Their growth was compared to that of 11 children given similar doses of cranial radiation only (group II). The mean plasma GH response to arginine-insulin test (AITT) was 9.1 +/- 1.5 (+/- SE) micrograms/L in group I and 8.5 +/- 1.8 micrograms/L in group II (P = NS). After 2 yr, 16 of the 27 children had a peak plasma GH value below 8 micrograms/L after AITT, and 10 children had a peak response less than 5 micrograms/L. In addition, in group I, AITT and sleep-related GH secretion were compared; at the 2 yr follow-up only 3 of 13 children had discrepant results. At the 2 yr follow-up children treated by cranial and spinal radiation had a mean height of -1.46 +/- 0.40 SD below the normal mean. In contrast, the children given only cranial radiation had a mean height of -0.15 +/- 0.18 SD; P less than 0.02. Therefore, most of the growth retardation appeared to be due to lack of spinal growth. GHD is thus an early complication of cranial radiation in these children, and no significant growth retardation can be attributed to GHD during the first 2 yr. These data contribute to the organization of follow-up in irradiated children in order to decide when human GH treatment is necessary.

  8. Differential effects of insufflated, subcutaneous, and intravenous growth hormone on bone growth, cognitive function, and NMDA receptor subunit expression.

    PubMed

    Park, Sung Won; Shin, Sooyoung; Kim, Chi Hwa; Ko, Ah-ra; Kwak, Min Jung; Nam, Mi Hyun; Park, So Young; Kim, Su Jin; Sohn, Young Bae; Galinsky, Raymond E; Kim, Hojoong; Yeo, Yoon; Jin, Dong-Kyu

    2010-09-01

    The objective of this study was to characterize the effect of inhalable growth hormone (GH) delivered by an insufflator to the lungs of hypophysectomized Sprague Dawley rats. In the first cohort, the safety and efficacy of the insufflated GH were evaluated. Three experimental groups (n = 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 microg/kg (SC200). Two other groups received GH by insufflation daily: 200 microg/kg (INS 200) and 600 microg/kg (INS 600). In the second set of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n=10) for 5 d, and escape latency and N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity as SC200 in growth promotion, tibial growth, as well as escape latency on the 12th day of treatment. Insufflated GH was well tolerated without significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampus measured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with the improvement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, and its bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properly to human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpression of NMDA receptors. PMID:20610568

  9. Interaction of growth hormone-releasing hormone with the insulin-like growth-factors during prenatal development in the rat.

    PubMed

    Spatola, E; Pescovitz, O H; Marsh, K; Johnson, N B; Berry, S A; Gelato, M C

    1991-09-01

    The placenta is a chimeric organ that produces all the components of the hypothalamic-pituitary GH axis. We propose that placental GH-releasing hormone (GHRH) stimulates placental GH-like hormones which in turn stimulate production of the insulin-like growth factors (IGFs), IGF-I and IGF-II, and these placental IGFs are important for growth and development of the placenta as well as the fetus. To test this hypothesis, pregnant rats were given either GHRH antisera or preimmune sera ip from days 7-19 of gestation. Fetuses were killed on day 19, and IGF-I and IGF-II tissue and serum concentrations in the mother and fetus were measured by RIA. IGF-II receptor content was measured by Western analysis. IGF-I and IGF-II messenger (m) RNA levels were measured in the placentas as well as in the fetal livers. The GHRH antibody titer was highest at day 19 of gestation but continued to be present through day 20 of postnatal development. Although placental weights did not differ, antibody-treated animals had higher placental IGF-I and IGF-II levels (I, 108 +/- 6 (SD); II, 126 +/- 5 ng/g, respectively) vs. control animals (I, 88 +/- 2.5 (SD); II, 48 +/- 11 ng/g) in pooled specimens. The IGF-II receptor was also up-regulated in placentas from antibody-treated mothers. The fetuses of antibody-treated (A) mothers were larger than the controls (C) (A, 2.615 g; C, 2.49 g, P less than 0.05). Levels of both IGFs were significantly increased in livers of antibody treated fetuses (IGF-I: A, 15 +/- 1 (SD); C, 12 +/- 0.8 ng/g; and IGF-II: A, 295 +/- 10 (SD); C, 233 +/- 10 (SD) ng/g). In addition, the concentration of the IGF-II receptor in liver of antibody-treated fetuses was also increased. Further, pooled fetal sera from antibody-treated fetuses had higher levels of IGF-II than controls (A, 950 ng/ml; C, 700 ng/ml), and the circulating IGF-II receptor was increased as measured by Western analysis. In the liver, IGF-II mRNA levels of antibody-treated fetuses were increased to 117% of

  10. Positive nitrogen balance with human growth hormone and hypocaloric intravenous feeding.

    PubMed

    Manson, J M; Wilmore, D W

    1986-08-01

    Nitrogen equilibrium cannot be achieved in surgical patients without adequate nitrogen and calorie intake, frequently requiring central venous feedings. To investigate the hormonal environment under which nitrogen retention might be achieved during hypocaloric feedings, we administered peripheral vein nutrition with growth hormone (GH) to four healthy male patients. The intravenous diets provided 50% of estimated energy requirements (mean 566 kcal/m2/day) and adequate nitrogen (6 gm/m2/day). Each subject was studied for two 7-day periods; 10 mg of GH was given daily during one period and placebo during the other. Administration of GH decreased weight loss, caused retention of nitrogen, potassium, and phosphorus in amounts closely matching their proportions in skeletal muscle, and stimulated insulin production. GH also raised serum levels of free fatty acids and glycerol, increased urinary excretion of ketones, and favored fat oxidation in the postabsorptive state. Hyperinsulinemia and increased lipolysis and ketogenesis may augment the primary effects of GH. Further studies at adequate and approximately 30% of adequate calorie intake confirmed these findings. Maintenance of body protein with GH may allow improved nutritional care of catabolic patients that was previously unrecognized. PMID:3090723

  11. Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules.

    PubMed

    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

  12. 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

  13. 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.

  14. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    NASA Technical Reports Server (NTRS)

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

    1998-01-01

    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  15. Preparation, characterization and molecular modeling of PEGylated human growth hormone with agonist activity.

    PubMed

    Khameneh, Bahman; Jaafari, Mahmoud Reza; Hassanzadeh-Khayyat, Mohammad; Varasteh, AbdolReza; Chamani, JamshidKhan; Iranshahi, Mehrdad; Mohammadpanah, Hamid; Abnous, Khalil; Saberi, Mohammad Reza

    2015-09-01

    In this study, site-specific PEGylated human growth hormone (hGH) was prepared by microbial transglutaminase, modeled and characterized. To this end, the effects of different reaction parameters including reaction media, PEG:protein ratios, reaction time and pH value were investigated. PEG-hGH was purified by size exclusion chromatography method and analyzed by SDS-PAGE, BCA, peptide mapping, ESI and MALDI-TOF-TOF mass spectroscopy methods. Biophysical and biological properties of PEG-hGH were evaluated. Molecular simulation was utilized to provide molecular insight into the protein-receptor interaction. The optimum conditions that were obtained for PEGylation were phosphate buffer with pH of 7.4, 48 h of stirring and PEG:protein ratio of 40:1. By this method, mono-PEG-hGH with high reaction yield was obtained and PEGylation site was at Gln-40 residue. The circular dichroism and fluorescence spectrum indicated that PEGylation did not change the secondary structure while tertiary structure was altered. Upon enzymatic PEGylation, agonistic activity of hGH was preserved; however, Somavert(®), which is prepared by chemical PEGylation, is an antagonist form of protein. These data were confirmed by the total energy of affinity obtained by computational protein-receptor interaction. In conclusion, PEGylation of hGH was led to prepare a novel form of hormone with an agonist activity which merits further investigations. PMID:26116386

  16. 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.

  17. Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications.

    PubMed

    Müller, E E; Rolla, M; Ghigo, E; Belliti, D; Arvat, E; Andreoni, A; Torsello, A; Locatelli, V; Camanni, F

    1995-11-01

    Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications. PMID:8586028

  18. Thyroid Hormone Regulates Hepatic Expression of Fibroblast Growth Factor 21 in a PPARα-dependent Manner*

    PubMed Central

    Adams, Andrew C.; Astapova, Inna; Fisher, ffolliott M.; Badman, Michael K.; Kurgansky, Katherine E.; Flier, Jeffrey S.; Hollenberg, Anthony N.; Maratos-Flier, Eleftheria

    2010-01-01

    Thyroid hormone has profound and diverse effects on liver metabolism. Here we show that tri-iodothyronine (T3) treatment in mice acutely and specifically induces hepatic expression of the metabolic regulator fibroblast growth factor 21 (FGF21). Mice treated with T3 showed a dose-dependent increase in hepatic FGF21 expression with significant induction at doses as low as 100 μg/kg. Time course studies determined that induction is seen as early as 4 h after treatment with a further increase in expression at 6 h after injection. As FGF21 expression is downstream of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα), we treated PPARα knock-out mice with T3 and found no increase in expression, indicating that hepatic regulation of FGF21 by T3 in liver is via a PPARα-dependent mechanism. In contrast, in white adipose tissue, FGF21 expression was suppressed by T3 treatment, with other T3 targets unaffected. In cell culture studies with an FGF21 reporter construct, we determined that three transcription factors are required for induction of FGF21 expression: thyroid hormone receptor β (TRβ), retinoid X receptor (RXR), and PPARα. These findings indicate a novel regulatory pathway whereby T3 positively regulates hepatic FGF21 expression, presenting a novel therapeutic target for diseases such as non-alcoholic fatty liver disease. PMID:20236931

  19. The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

    PubMed

    Rovenský, J; Blazícková, S; Rauová, L; Jezová, D; Koska, J; Lukác, J; Vigas, M

    1998-01-01

    It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects. PMID:9736325

  20. Hormonal regulation of epidermal growth factor and protease in the submandibular gland of the adult mouse.

    PubMed

    Gresik, E W; Schenkein, I; van der Noen, H; Barka, T

    1981-09-01

    The structure of the granular convoluted tubules of the mouse submandibular gland is influenced by androgens, adrenal steroids, and thyroid hormones. We wished to investigate the effects of variations in hormonal status on the quantitative and qualitative distribution of two secretory products of these tubules, epidermal growth factor (EGF) and protease. The effects of the thyroid and adrenal glands on EGF content and protease activity of the submandibular glands of adult female mice were studied by RIAs (EGF), enzyme assays (protease), and immunocytochemical methods. In animals rendered chronically hypothyroid by propylthiouracil (4 months) or in animals which were adrenalectomized and ovariectomized (3 weeks), protease activity and EGF levels were reduced by 81-97%. The administration of testosterone induced these polypeptides even in hypothyroid animals. Daily administration of L-T4 (T4; 1 micrograms/g BW) for 7 days increased EGF and protease activity 3.6-fold in intact mice and reversed the effect of hypothyroidism. EGF and protease were also induced by T4 in adrenalectomized and ovariectomized mice, although to a lesser degree than in intact animals. Immunocytochemical stainings of submandibular glands indicated that the number of granular convoluted tubule cells immunoreactive for EGF correlated with the levels of EGF determined by RIAs. With respect to immunostaining for protease, such a correlation was not observed. The data indicate multihormonal regulation of EGF and protease in the mouse submandibular gland. PMID:7021131

  1. Activation of a cryptic splice site in the growth hormone receptor associated with growth hormone insensitivity syndrome in a genetic isolate of Laron Syndrome

    SciTech Connect

    Schiavi, A.; Bartlett, R.; Brown, M.

    1994-09-01

    Laron syndrome (LS) is a rare, autosomal recessive disease found worldwide. Despite various ethnic differences, all patients with LS described display classic dysmorphic features and extreme short stature due to defects in the growth hormone receptor (GHR). The vast majority of these patients are sporadic occurrences resulting from consanguineous matings; however, an Ecuadorian genetic isolate of LS has been reported. Our investigations have identified a genetic isolate of LS of Anglo Saxon origin. Seven individuals, by all clinical and biochemical criteria, have LS. As a result of extensive review of family and medical histories we have constructed a pedigree tracing the lineage of our affected patients through the 17th century. No GHR gross deletions were detected using an exon-specific PCR assay developed in our laboratory. Previous molecular analyses have identified mutations in exons 2-7 in numerous patients with classical LS. Single strand conformational polymorphism (SSCP) analysis was performed on GHR exons 2-7, and a marked conformational shift was noted in exon 7. Cycle sequencing of exon 7 from three affected individuals, and from four first-degree relatives, revealed a C{r_arrow}T transition at position 766 of the cDNA, and a heterozygous C{r_arrow}T transition at the identical position in the obligate carriers studied. This mutation is predicted to activate a cryptic donor splice site 63 base pairs upstream from the 3{prime} end of exon 7, effectively truncating the GHR cDNA without changing the reading frame. The resultant GHR protein is shortened by a proposed 21 amino acids. The identification and conformation of this mutation not only identifies a novel mutation in the GHR, and the first to be described in LS patients of English descent, but also allows for comparisons between genotypes and phenotypes in an inbred population.

  2. Pathology, Pathogenesis and Therapy of Growth Hormone (GH)-producing Pituitary Adenomas: Technical Advances in Histochemistry and Their Contribution

    PubMed Central

    Osamura, Robert Y.; Egashira, Noboru; Kajiya, Hanako; Takei, Mao; Tobita, Maya; Miyakoshi, Takashi; Inomoto, Chie; Takekoshi, Susumu; Teramoto, Akira

    2009-01-01

    Growth hormone (GH)-producing adenomas (GHomas) are one of the most frequently-occurring pituitary adenomas. Differentiation of hormone-producing cells in the pituitary gland is regulated by transcription factors and co-factors. The transcription factors include Pit-1, Prop-1, NeuroD1, Tpit, GATA-2, SF-1. Aberrant expression of transcription factors such as Pit-1 results in translineage expression of GH in adrenocorticotropic hormone-producing adenomas (ACTHomas). This situation has been substantiated by GFP-Pit-1 transfection expression in the AtT20 cell line. Experimentally, GHomas have been induced in GH-releasing hormone (GHRH) or Prop-1 transgenic animals. Immunohistochemical detection of somatostatin receptor (SSTR2a) has recently emphasized their role in the response of GHomas to somatostatin analogue therapy. In this review, the advances in technology and their contribution to cell biology and medical practice are discussed. PMID:19759870

  3. Increased Metabolic Flexibility and Complexity in a Long-Lived Growth Hormone Insensitive Mouse Model

    PubMed Central

    2014-01-01

    The goal of this study was to test whether the “loss of the complexity” hypothesis can be applied to compare the metabolic patterns of mouse models with known differences in metabolic and endocrine function as well as life span. Here, we compare the complexity of locomotor activity and metabolic patterns (energy expenditure, VO2, and respiratory quotient) of the long-lived growth hormone receptor gene deleted mice (GHR− /−) and their wild-type littermates. Using approximate entropy as a measure of complexity, we observed greater metabolic complexity, as indicated by greater irregularity in the physiological fluctuations of the GHR− /− mice. Further analysis of the data also revealed lower energy costs of locomotor activity and a stronger relationship between locomotor activity and respiratory quotient in the GHR− /− mice relative to controls. These findings suggest underlying differences in metabolic modulation in the GHR− /− mice revealed especially through measures of complexity of their time-dependent fluctuations. PMID:23788654

  4. Cloning and sequencing of the growth hormone gene of large yellow croaker and its phylogenetic significance.

    PubMed

    Chen, Yun; Wang, Yaping; He, Shunping; Zhu, Zuoyan

    2004-10-01

    Using conserved primers and the PCR reaction, the growth hormone (GH) gene and the 3'-UTR of the large yellow croaker (Pseudosciaena crocea) were amplified and sequenced. The gene structure was analyzed and compared to the GH genes of 5 other percoid fish downloaded from Genbank. Also the GH gene of the large yellow croaker and the genes from 14 Percoidei and 2 Labroidei species were aligned using Clustal X. A matrix of 564 bp was used to construct the phylogenetic tree using maximum parsimony and neighbor-joining methods. Phylogenetic trees by the two methods are identical in most of the clades with high bootstrap support. The results are also identical to those from morphological data. In general, this analysis does not support the monophyll of the families Centropomidae and Carangidae. But our GH gene tree indicates that the representative species of the families Sparidae and Sciaenidae are a monophyletic group. PMID:15524313

  5. Receptor domains involved in signal transduction of prolactin and growth hormone

    SciTech Connect

    Kelly, P.A.; Edery, M.; Finidori, J.

    1994-12-31

    Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily that include receptors for a number of cytokines. GH and its receptor form an unusual homodimer consisting of one molecule of GH and two molecules of receptor. A similar homodimer of the PRL receptor is probably required for biological effects to be seen. Using specific assays to measure the functional activity of PRL and GH receptors, a 25 amino acid juxtamembrane region has been identified as essential but not sufficient for normal action. More detailed studies have limited the region to eight amino acids, rich in prolines, that is highly conserved in many members of the receptor superfamily. Finally, GH and PRL have been shown to induce the rapid tyrosine phosphorylation of an associated kinase, Janus kinase 2, and of the receptor itself. 28 refs., 1 fig.

  6. Changes in pituitary growth hormone cells prepared from rats flown on Spacelab 3

    NASA Technical Reports Server (NTRS)

    Grindeland, R.; Hymer, W. C.; Farrington, M.; Fast, T.; Hayes, C.; Motter, K.; Patil, L.; Vasques, M.

    1987-01-01

    The effect of exposure to microgravity on pituitary gland was investigated by examining cells isolated from anterior pituitaries of rats flown on the 7-day Spacelab 3 mission and, subsequently, cultured for 6 days. Compared with ground controls, flight cells contained more intracellular growth hormone (GH); however, the flight cells released less GH over the 6-day culture period and after implantation into hypophysectomized rats than did the control cells. Compared with control rats, glands from large rats (400 g) contained more somatotrophs (44 percent compared with 37 percent in control rats); small rats (200 g) showed no difference. No major differences were found in the somatotroph ultrastructure (by TEM) or in the pattern of the immunoactive GH variants. However, high-performance liquid chromatography fractionation of culture media indicated that flight cells released much less of a biologically active high-molecular weight GH variant, suggesting that space flight may lead to secretory dysfunction.

  7. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism.

    PubMed

    Ilias, Chatziioannidis; Evgenia, Babatseva; Aikaterini, Patsatsi; Asimina, Galli-Tsinopoulou; Constantina, Sarri; Maria, Lithoxopoulou; George, Mitsiakos; Paraskevi, Karagianni; Christos, Tsakalidis; Zissis, Mamuris; Nikolaos, Nikolaidis

    2015-01-01

    Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH) deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications. PMID:26229701

  8. Growth hormone therapy for Prader-Willi and Down syndromes: a post-modern medical dilemma.

    PubMed

    Lantos, J D

    2000-04-01

    Post-modernism means the end of traditional certainties. In this paper, growth hormone (GH) is conceptualized as a post-modern medical therapy. It is used in the treatment of conditions that are not traditional diseases, for indications that are not precisely defined. Down syndrome and Prader-Willi syndrome represent two clinical conditions in which GH can possibly be used. It is argued that the difference between the two syndromes instructs us as to the principles that might guide appropriate use of GH in the future. In particular, for children, the more GH treatment can be shown to produce benefits other than increased height, the more justifiable its use will be. PMID:10984261

  9. Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications.

    PubMed

    Kopchick, John J; List, Edward O; Kelder, Bruce; Gosney, Elahu S; Berryman, Darlene E

    2014-04-01

    The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer. PMID:24035867

  10. 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

  11. Usefulness of urinary growth hormone (GH) measurement for evaluating endogenous GH secretion in acromegaly.

    PubMed

    Mauri, M; Picó, A M; Alfayate, R; Dominguez, J R; Cámara, R; Miralles, C

    1993-01-01

    We investigated the relationship between urinary growth hormone (u-GH) and spontaneous 24-hour plasma GH secretion in 15 acromegalic patients. To measure u-GH, we have developed a method based on concentrating the sample by centrifugal ultrafiltration and then performing an immunoradiometric assay using commercially available reagents. u-GH correlated well with the integrated concentration of plasma GH (r = 0.66, p < 0.02). Additionally, u-GH excretion in acromegalic patients was significantly higher than in the control group (190 +/- 100 vs. 3.89 +/- 0.56 pg/min, mean +/- SEM, p < 0.001). Immunoreactive u-GH showed the same elution pattern in Sephadex G-75 as standard or labeled hGH, proving that the substance measured in urine is authentic GH. In conclusion, u-GH appears to be a simple, noninvasive and inexpensive test for evaluating GH secretion in active acromegaly. PMID:8406334

  12. Comorbid Medical Conditions in Friedreich Ataxia: Association With Inflammatory Bowel Disease and Growth Hormone Deficiency.

    PubMed

    Shinnick, Julianna E; Schadt, Kimberly; Strawser, Cassandra; Wilcox, Nicholas; Perlman, Susan L; Wilmot, George R; Gomez, Christopher M; Mathews, Katherine D; Yoon, Grace; Zesiewicz, Theresa; Hoyle, Chad; Subramony, S H; Yiu, Eppie M; Delatycki, Martin B; Brocht, Alicia F; Farmer, Jennifer M; Lynch, David R

    2016-08-01

    Friedreich ataxia is a progressive degenerative disease with neurologic and cardiac involvement. This study characterizes comorbid medical conditions in a large cohort of patients with Friedreich ataxia. Patient diagnoses were collected in a large natural history study of 641 subjects. Prevalence of diagnoses in the cohort with Friedreich ataxia was compared with prevalence in the population without Friedreich ataxia. Ten patients (1.6%) had inflammatory bowel disease, 3.5 times more common in this cohort of individuals with Friedreich ataxia than in the general population. Four subjects were growth hormone deficient, reflecting a prevalence in Friedreich ataxia that is 28 times greater than the general population. The present study identifies specific diagnoses not traditionally associated with Friedreich ataxia that are found at higher frequency in this disease. These associations could represent coincidence, shared genetic background, or potentially interactive disease mechanisms with Friedreich ataxia. PMID:27071470

  13. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism

    PubMed Central

    Ilias, Chatziioannidis; Evgenia, Babatseva; Aikaterini, Patsatsi; Asimina, Galli-Tsinopoulou; Constantina, Sarri; Maria, Lithoxopoulou; George, Mitsiakos; Paraskevi, Karagianni; Christos, Tsakalidis; Zissis, Mamuris; Nikolaos, Nikolaidis

    2015-01-01

    Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH) deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications. PMID:26229701

  14. Familial X-linked mental retardation and isolated growth hormone deficiency: Clinical and molecular findings

    SciTech Connect

    Hamel, B.C.J.; Smits, A.P.T.; Helm, B. van den

    1996-07-12

    We report on several members of a family with varying degrees of X-linked mental retardation (XLMR), isolated growth hormone deficiency (IGHD), and infantile behavior but without other consistent phenotypic abnormalities. Male patients continued to grow until well into their twenties and reached a height ranging from 135 to 159 cm. Except one, all female carriers were mentally normal; their adult height ranged from 159 to 168 cm. By linkage studies we have assigned the underlying genetic defect to the Xq24-q27.3 region, with a maximum lod score of Z = 3.26 at {theta} = 0.0 for the DXS294 locus. The XLMR-IGHD phenotype in these patients may be due to pleiotropic effects of a single gene or it may represent a contiguous gene syndrome. 18 refs., 6 figs., 3 tabs.

  15. Heavy metal interference with growth hormone signalling in trout hepatoma cells RTH-149.

    PubMed

    Marchi, Barbara; Burlando, Bruno; Panfoli, Isabella; Dondero, Francesco; Viarengo, Aldo; Gallo, Gabriella

    2005-04-01

    We have studied the effects of heavy metals (Hg2+, Cu2+, Cd2+) on growth hormone (GH) activation of tyrosine kinase and Ca2+ signaling in the trout (Oncorhynchus mykiss) hepatoma cell line RTH-149. Molecular cloning techniques using primer designed on Oncorhynchus spp. growth hormone receptor (GHR) genes allowed to isolate a highly homologous cDNA fragment from RTH-149 mRNA. Thereafter, cells were analysed by Western blotting or, alternatively, with Ca2+ imaging using fura-2/AM. Exposure of cells to ovine GH alone produced a stimulation of the JAK2/STAT5 pathway and intracellular free Ca2+ variations similar to what has been observed in mammalian models. Cell pre-exposure to Cu2+, Hg2+ or Cd2+ affected cell response to GH by enhancing (Cu2+) or inhibiting (Cd2+) the phosphorylation of JAK2 and STAT5. Heavy metals induced the activation of the MAP kinase p38, and pre-exposure to Hg2+ or Cu2+ followed by GH enhanced the effect of metal alone. Image analysis of fura2-loaded cells indicated that pre-treatment with Hg2+ prior to GH produced a considerable increase of the [Ca2+]i variation produced by either element, while using Cu2+ or Cd2+ the result was similar but much weaker. Data suggest that heavy metals interfere with GH as follows: Hg2+ is nearly ineffective on JAK/STAT and strongly synergistic on Ca2+ signaling; Cu2+ is activatory on JAK/STAT and slightly activatory on Ca2+; Cd2+ is strongly inhibitory on JAK/STAT and slightly activatory on Ca2+; heavy metals could partially activate STAT via p38 independently from GH interaction. PMID:15954744

  16. Effect of supplemental light on growth, prolactin, progesterone and luteinizing hormone in water buffalo ( Bubalus bubalis)

    NASA Astrophysics Data System (ADS)

    Perera, K. S.; Gwazdauskas, F. C.; Akers, R. M.; McGilliard, M. L.

    1989-06-01

    Fifty non-pregnant Surti buffalo heifers aged between 17 and 42 months ( n=24, <24 months; n=26, >24 months) were randomly assigned to groups subject to either natural daylight +4h supplemental light ( n=25) or natural day light ( n=25), to study changes in growth, serum prolactin (Prl), progesterone (P4) and luteinizing hormone (LH) to supplemental lighting. Ambient temperatures (T) and relative humidity (RH) generally were >27° C and <70% during the day-time, respectively. Light-supplemented heifers had 16.2 kg net body weight (BW) gain at 9 weeks compared to 20.8 kg for controls, but higher mean Prl after 6.5 weeks ( P<0.01), and higher P4 (0.41 vs 0.19 ng/ml; P<0.06) than control heifers. Older heifers had 39.7% greater BW ( P<0.01), but a net 4.3% BW gain compared to a 10.1% gain for younger heifers at 10 weeks. Older, light-supplemented heifers had higher mean P4 (0.63 vs 0.19 ng/ml; P<0.07) than the other groups. These weight and hormonal changes suggest that 4 h supplemental light can alter growth and endocrine function in buffaloes under similar planes of nutrition. While light supplementation did not have a positive effect on body wieght during the 10 week study, body weight and endocrine changes due to supplemental light may be important factors for initiation of reproductive cyclicity.

  17. Effects of Hypergravity Rearing on Growth Hormone (GH) Secretion In Preweanling Rats

    NASA Technical Reports Server (NTRS)

    Baer, L. A.; Chowdhury, J. H.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    We previously reported that rat pups reared at 1.5-g, 1.75 or 2.0-g hypergravity weigh 6-15% less than 1.0-g controls. To account for these findings. we measured the lactational hormones, prolaction (Prl) and oxytocin (OT), in the pups' mothers. Gravity related differences in Prl were not observed whereas OT of lactating dams was significantly reduced relative to controls. Milk transfer from dam to pup was not impaired in hypergravity-reared litters tested at 1-g. Together, these findings suggest that impaired lactation and milk transfer do not account for reduced body masses of postnatal rats reared in hypergravity. In the present study, we analyzed growth hormone (GH) secretion and maternal licking in pups reared in hypergravity and in 1.0-g controls. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on GH and insulin-like growth factors (IGFs). Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were exposed to either 1.5-g, 1.75-g or 2.0-g. On Postnatal day (P)10, we measured plasma GH using enzyme immunoassay (EIA). Contrary to our hypothesis, GH was significantly elevated in pups reared at 2.0-g relative to 1.0-g controls. Pup-oriented behaviors of the hypergravity dams were also changed, possibly accounting for the increase in pup GH. GH alone does not appear to play a role in reduced body weights of hypergravity-reared pups.

  18. In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells.

    PubMed

    Cuny, Thomas; Zeiller, Caroline; Bidlingmaier, Martin; Défilles, Céline; Roche, Catherine; Blanchard, Marie-Pierre; Theodoropoulou, Marily; Graillon, Thomas; Pertuit, Morgane; Figarella-Branger, Dominique; Enjalbert, Alain; Brue, Thierry; Barlier, Anne

    2016-07-01

    Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs (SSAs) and/or uncontrolled by transsphenoidal surgery. The residual GH-secreting tumor is therefore exposed to the action of circulating PEG. However, the biological effect of PEG at the pituitary level remains unknown. To assess the impact of PEG in vitro on the hormonal secretion (GH and prolactin (PRL)), proliferation and cellular viability of eight human GH-secreting tumors in primary cultures and of the rat somatolactotroph cell line GH4C1. We found that the mRNA expression levels of GHR were characterized in 31 human GH-secreting adenomas (0.086 copy/copy β-Gus) and the GHR was identified by immunocytochemistry staining. In 5/8 adenomas, a dose-dependent inhibition of GH secretion was observed under PEG with a maximum of 38.2±17% at 1μg/mL (P<0.0001 vs control). A dose-dependent inhibition of PRL secretion occurred in three mixed GH/PRL adenomas under PEG with a maximum of 52.8±11.5% at 10μg/mL (P<0.0001 vs control). No impact on proliferation of either human primary tumors or GH4C1 cell line was observed. We conclude that PEG inhibits the secretion of GH and PRL in primary cultures of human GH(/PRL)-secreting pituitary adenomas without effect on cell viability or cell proliferation. PMID:27267119

  19. Growth hormone therapy and risk of recurrence/progression in intracranial tumors: a meta-analysis.

    PubMed

    Shen, Liang; Sun, Chun Ming; Li, Xue Tao; Liu, Chuan Jin; Zhou, You Xin

    2015-10-01

    Growth hormone deficiency is common in intracranial tumors, which is usually treated with surgery and radiotherapy. A number of previous studies have investigated the relationship between the growth hormone replacement therapy (GHRT) and risk of tumor recurrence/progression; however, the evidence remains controversial. We conducted a meta-analysis of published studies to estimate the potential relation between GHRT and intracranial tumors recurrence/progression. Three comprehensive databases, PUBMED, EMBASE, and Cochrane Library, were researched with no limitations, covering all published studies till the end of July, 2014. Reference lists from identified studies were also screened for additional database. The summary relative risks (RR) and 95% confidence intervals (CI) were calculated by fixed-effects models for estimation. Fifteen eligible studies, involving more than 2232 cases and 3606 controls, were included in our meta-analysis. The results indicated that intracranial tumors recurrence/progression was not associated with GHRT (RR 0.48, 95% CI 0.39-0.56), and for children, the pooled RR was 0.44 and 95% CI was 0.34-0.54. In subgroup analysis, risks of recurrence/progression were decreased for craniopharyngioma, medulloblastoma, astrocytoma, glioma, but not for pituitary adenomas, and non-functioning pituitary adenoma (NFPA), ependymoma. Results from our analysis indicate that GHRT decreases the risk of recurrence/progression in children with intracranial tumors, craniopharyngioma, medulloblastoma, astrocytoma, or glioma. However, GHRT for pituitary adenomas, NFPA, and ependymoma was not associated with the recurrence/progression of the tumors. GH replacement seems safe from the aspect of risk of tumor progression. PMID:26048536

  20. [A pathologic study of adenohypophyseal growth hormone cells in the rabbit after severe burn].

    PubMed

    Wu, J

    1989-06-01

    The growth hormone(GH), produced by the growth hormone cell in pars distalis of the adenohypophysis, acts on the sugar, protein and fat metabolism in various degrees. After trauma, the GH has relations with the energy supply, the maintenance of nitrogen balance, the tissue repair and the body resistance. However, pathological study on the GH cell after burn injury is rare in the literature so far. The purpose of the present investigation is to take a dynamic observation on the ultrastructural changes of the rabbit GH cell after napalm burn within one week. 46 male rabbits were used and divided into two groups, napalm burn group (N = 36) and control group (N = 10). The former is inflicted with 3rd degree burn covering 30% TBSA. The animals of former group were sacrificed at 3, 6, 12, 24, 48, 72, 96, 120, 168 hours postburn respectively. Using the light and electron microscopy and stereological method, the results revealed that: (1) the synthesis activity in GH cell was enhanced, the process of secretion was rapid, and the rate of granule maturation was increased; (2) the nude GH granules were found both in the sinusoids and the endothelial cells; (3) the newly formed mitochondria may be originated from the Golgi complex, and the newly formed Golgi complex from the reutilization of the plasma membrane components; (4) some endothelial cells manifested degeneration, and the others showed in active condition; (5) under the light microscopy, the distribution of the lower tint-phil GH cells had its regional-characteristics. PMID:2509038

  1. Acid denaturation of recombinant porcine growth hormone: formation and self-association of folding intermediates.

    PubMed

    Parkinson, E J; Morris, M B; Bastiras, S

    2000-10-10

    We have investigated the conformational changes incurred during the acid-induced unfolding and self-association of recombinant porcine growth hormone (pGH). Acidification (pH 8 to pH 2) of pGH resulted in intrinsic fluorescence, UV absorbance, and near-UV CD transitions centered at pH 4.10. At pH 2.0, a red shift in the fluorescence emission maximum of approximately 3 nm and a 15% loss of the far-UV CD signal at 222 nm imply that the protein did not become extensively unfolded. Acidification in the presence of 4 M urea resulted in similar pH-dependent transitions. However, these occurred at a higher pH (approximately 5.2). At pH 2.0 + 4 M urea, an 8 nm red shift in the fluorescence emission maximum suggests that unfolding was greater than in the absence of urea. The presence of a prominent peak centered at 298 nm in the near-UV CD spectrum, which is absent without urea, signifies further differences in the intermediates generated at pH 2. Sedimentation equilibrium experiments in the analytical ultracentrifuge showed that native pGH and the partially unfolded intermediates reversibly self-associate. Self-association was strongly promoted at pH 2 while urea reduced self-association at both pH 8 and pH 2. These results demonstrate that acidification of pGH in the absence or presence of 4 M urea induced the formation of molten globule-like states with measurable differences in conformation. Similarities and differences in these structural conformations with respect to other growth hormones are discussed. PMID:11015214

  2. Biosynthetic growth hormone increases the collagen deposition rate in rat aorta and heart.

    PubMed

    Brüel, A; Oxlund, H

    1995-02-01

    Disorders of the cardiovascular system often are associated with alterations in the metabolism of the collagens of these tissues. A method for in vivo determination of collagen deposition rate in small tissue samples is delineated and used for assessment of the effect of biosynthetic growth hormone (GH) injections on the collagen deposition rate in rat aorta and cardiac musculature. Rats were injected with GH, and the controls with saline, twice daily for 7 days. The in vivo collagen deposition rate was measured by injecting iv a large dose of [3H]-proline with a flooding dose of "cold" proline, followed by determination of the production of [3H]-hydroxyproline during a 4-h labelling period. Extractable collagens that were not bound in the tissue and therefore do not contribute mechanical strength to it were removed from the samples. 3H-Labelled- and "cold" amino acids were assessed by reversed-phase HPLC combined with simultaneous flow scintillation detection on the same sample. In the control group the deposition per hour was 0.13 +/- 0.02% (mean +/- SEM) in aortic intima media and 0.72 +/- 0.09% in cardiac left ventricular musculature. Growth hormone induced a threefold increase (p < 0.001 and p < 0.01, respectively) in the collagen deposition rate: 0.45 +/- 0.06% in aortic intima media and 2.43 +/- 0.45% in cardiac left ventricular musculature. The method described enables a rapid and sensitive determination of collagen deposition per hour in small tissue samples from experimental animals. The collagen deposition rate of cardiac musculature is fivefold higher compared with that of aortic intima media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7858738

  3. Surface plasmon resonance biosensor for direct detection of antibodies against human growth hormone.

    PubMed

    Kausaite-Minkstimiene, Asta; Ramanaviciene, Almira; Ramanavicius, Arunas

    2009-10-01

    A direct, label-free detection method of antibodies against the human growth hormone (anti-HGH) using a surface plasmon resonance (SPR) biosensor is reported. The sensing surface of the surface plasmon resonance biosensor chip (SPR-chip) was modified by covalent coupling of the human growth hormone (HGH) to the self-assembled monolayer of 11-mercaptoundecanoic acid (MUA). HGH was immobilized via primary amine groups after activation of the MUA carboxyl groups with a mixture of N-hydroxysuccinimide (NHS), and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). The specific binding of monoclonal anti-HGH antibody on the HGH-modified surface was examined in the concentration range from 0.25 nM to 10 microM. The experimentally observed detection minimum for anti-HGH was 2.47 nM. A single immunoassay cycle could be done within 30 min including the HGH and anti-HGH association, HGH/anti-HGH complex dissociation and surface regeneration steps. The SPR biosensor response for repeatable detections of anti-HGH was highly reproducible and very stable. On the SPR-chip the formed HGH and anti-HGH complex (HGH/anti-HGH) could be gently dissociated and the sensing surface might be regenerated by 50 mM NaOH and 0.5% sodium dodecylsulfate (SDS) solution. Any changes in the original baseline level were detected during the 40 detection-regeneration cycles. This means that damage of the immobilized HGH-based sensitive layer during regeneration was minimal. It was demonstrated that the developed SPR-chip could be stored for at least 21 days before use without considerable loss of sensitivity towards anti-HGH. PMID:19768212

  4. Reduction of lung distensibility in acromegaly after suppression of growth hormone hypersecretion.

    PubMed

    García-Río, F; Pino, J M; Díez, J J; Ruíz, A; Villasante, C; Villamor, J

    2001-09-01

    Whether the growth of the lungs in acromegaly is due to alveolar hypertrophy or alveolar hyperplasia is a subject of debate. To discriminate these hypotheses, we compared pulmonary distensibility and diffusing capacity among 11 patients with active acromegaly and 11 matched control subjects, evaluating the response of pulmonary distensibility and diffusing capacity to suppression of growth hormone (GH) hypersecretion. We performed lineal and exponential analyses of quasistatic pressure-volume curves. Patients with active acromegaly had a greater TLC, lung compliance, and shape constant, K, than did normal subjects. We found no significant differences between the study groups in carbon monoxide diffusing capacity or diffusing capacity per unit of alveolar volume. After treatment, patients with inactive acromegaly showed a reduced TLC (6.95 +/- 1.40 [mean +/- SD] L versus 6.35 +/- 1.23 L), reduced lung compliance (3.61 +/- 0.90 L/kPa versus 2.36 +/- 0.79 L/ kPa), reduced K coefficient (2.62 +/- 0.65 kPa(-)(1) versus 1.35 +/- 0.40 kPa(-)(1)), and increased maximal recoil pressure (1.74 +/- 0.38 kPa versus 2.28 +/- 0.25 kPa). We conclude that the increased lung distensibility with normal diffusion capacity demonstrated in patients with active acromegaly, which was partly reversible after suppression of GH hypersecretion, suggests that lung growth in acromegaly may result from an increase in alveolar size. PMID:11549545

  5. 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.

  6. Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary.

    PubMed

    Durlinger, Alexandra L L; Gruijters, Maria J G; Kramer, Piet; Karels, Bas; Ingraham, Holly A; Nachtigal, Mark W; Uilenbroek, Jan Th J; Grootegoed, J Anton; Themmen, Axel P N

    2002-03-01

    Recruitment of primordial follicles is essential for female fertility; however, the exact mechanisms regulating this process are largely unknown. Earlier studies using anti-Müllerian hormone (AMH)-deficient mice suggested that AMH is involved in the regulation of primordial follicle recruitment. We tested this hypothesis in a neonatal ovary culture system, in which ovaries from 2-d-old C57Bl/6J mice were cultured for 2 or 4 d in the absence or presence of AMH. Ovaries from 2-d-old mice contain multiple primordial follicles, some naked oocytes, and no follicles at later stages of development. We observed that in the cultured ovaries, either nontreated or AMH-treated, follicular development progressed to the same extent as in in vivo ovaries of comparable age, confirming the validity of our culture system. However, in the presence of AMH, cultured ovaries contained 40% fewer growing follicles compared with control ovaries. A similar reduction was found after 4 d of culture. Consistent with these findings, we noted lower inhibin alpha-subunit expression in AMH-treated ovaries compared with untreated ovaries. In contrast, expression of AMH ligand type II receptor and the expression of oocyte markers growth and differentiation factor 9 and zona pellucida protein 3 were not influenced by AMH. Based on the results, we suggest that AMH inhibits initiation of primordial follicle growth and therefore functions as an inhibitory growth factor in the ovary during these early stages of folliculogenesis. PMID:11861535

  7. 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.

  8. 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

  9. The inhibitory effects of interleukin-1 on growth hormone action during catabolic illness.

    PubMed

    Cooney, Robert N; Shumate, Margaret

    2006-01-01

    Growth hormone (GH) induces the expression of the anabolic genes responsible for growth, metabolism, and differentiation. Normally, GH stimulates the synthesis of circulating insulin-like growth factor-I (IGF-I) by liver, which upregulates protein synthesis in many tissues. The development of GH resistance during catabolic illness or inflammation contributes to loss of body protein, resulting in multiple complications that prolong recovery and cause death. In septic patients, increased levels of proinflammatory cytokines and GH resistance are commonly observed together. Numerous studies have provided evidence that the inhibitory effects of cytokines on skeletal muscle protein synthesis during sepsis and inflammation are mediated indirectly by changes in the GH/IGF-I system. Interleukin (IL)-1, a member of the family of proinflammatory cytokines, interacts with most cell types and is an important mediator of the inflammatory response. Infusion of a specific IL-1 receptor antagonist (IL-1Ra) ameliorates protein catabolism and GH resistance during systemic infection. This suggests that IL-1 is an important mediator of GH resistance during systemic infection or inflammation. Consequently, a better understanding of the interaction between GH, IL-1, and the regulation of protein metabolism is of great importance for the care of the patient. PMID:17027521

  10. LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice

    PubMed Central

    Touvier, Thierry; Conte-Auriol, Françoise; Briand, Olivier; Cudejko, Céline; Paumelle, Réjane; Caron, Sandrine; Baugé, Eric; Rouillé, Yves; Salles, Jean-Pierre; Staels, Bart; Bailleul, Bernard

    2009-01-01

    Growth hormone (GH) is a major metabolic regulator that functions by stimulating lipolysis, preventing protein catabolism, and decreasing insulin-dependent glucose disposal. Modulation of hepatic sensitivity to GH and the downstream effects on the GH/IGF1 axis are important events in the regulation of metabolism in response to variations in food availability. For example, during periods of reduced nutrient availability, the liver becomes resistant to GH actions. However, the mechanisms controlling hepatic GH resistance are currently unknown. Here, we investigated the role of 2 tetraspanning membrane proteins, leptin receptor overlapping transcript (LEPROT; also known as OB-RGRP) and LEPROT-like 1 (LEPROTL1), in controlling GH sensitivity. Transgenic mice expressing either human LEPROT or human LEPROTL1 displayed growth retardation, reduced plasma IGF1 levels, and impaired hepatic sensitivity to GH, as measured by STAT5 phosphorylation and Socs2 mRNA expression. These phenotypes were accentuated in transgenic mice expressing both proteins. Moreover, gene silencing of either endogenous Leprot or Leprotl1 in H4IIE hepatocytes increased GH signaling and enhanced cell-surface GH receptor. Importantly, we found that both LEPROT and LEPROTL1 expression were regulated in the mouse liver by physiologic and pathologic changes in glucose homeostasis. Together, these data provide evidence that LEPROT and LEPROTL1 influence liver GH signaling and that regulation of the genes encoding these proteins may constitute a molecular link between nutritional signals and GH actions on body growth and metabolism. PMID:19907080

  11. LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice.

    PubMed

    Touvier, Thierry; Conte-Auriol, Françoise; Briand, Olivier; Cudejko, Céline; Paumelle, Réjane; Caron, Sandrine; Baugé, Eric; Rouillé, Yves; Salles, Jean-Pierre; Staels, Bart; Bailleul, Bernard

    2009-12-01

    Growth hormone (GH) is a major metabolic regulator that functions by stimulating lipolysis, preventing protein catabolism, and decreasing insulin-dependent glucose disposal. Modulation of hepatic sensitivity to GH and the downstream effects on the GH/IGF1 axis are important events in the regulation of metabolism in response to variations in food availability. For example, during periods of reduced nutrient availability, the liver becomes resistant to GH actions. However, the mechanisms controlling hepatic GH resistance are currently unknown. Here, we investigated the role of 2 tetraspanning membrane proteins, leptin receptor overlapping transcript (LEPROT; also known as OB-RGRP) and LEPROT-like 1 (LEPROTL1), in controlling GH sensitivity. Transgenic mice expressing either human LEPROT or human LEPROTL1 displayed growth retardation, reduced plasma IGF1 levels, and impaired hepatic sensitivity to GH, as measured by STAT5 phosphorylation and Socs2 mRNA expression. These phenotypes were accentuated in transgenic mice expressing both proteins. Moreover, gene silencing of either endogenous Leprot or Leprotl1 in H4IIE hepatocytes increased GH signaling and enhanced cell-surface GH receptor. Importantly, we found that both LEPROT and LEPROTL1 expression were regulated in the mouse liver by physiologic and pathologic changes in glucose homeostasis. Together, these data provide evidence that LEPROT and LEPROTL1 influence liver GH signaling and that regulation of the genes encoding these proteins may constitute a molecular link between nutritional signals and GH actions on body growth and metabolism. PMID:19907080

  12. Antagonistic actions of analogs related to growth hormone-releasing hormone (GHRH) on receptors for GHRH and vasoactive intestinal peptide on rat pituitary and pineal cells in vitro

    PubMed Central

    Rekasi, Zoltan; Varga, Jozsef L.; Schally, Andrew V.; Halmos, Gabor; Groot, Kate; Czompoly, Tamas

    2000-01-01

    Peptide analogs of growth hormone-releasing hormone (GHRH) can potentially interact with vasoactive intestinal peptide (VIP) receptors (VPAC1-R and VPAC2-R) because of the structural similarities of these two hormones and their receptors. We synthesized four new analogs related to GHRH (JV-1–50, JV-1–51, JV-1–52, and JV-1–53) with decreased GHRH antagonistic activity and increased VIP antagonistic potency. To characterize various peptide analogs for their antagonistic activity on receptors for GHRH and VIP, we developed assay systems based on superfusion of rat pituitary and pineal cells. Receptor-binding affinities of peptides to the membranes of these cells were also evaluated by radioligand competition assays. Previously reported GHRH antagonists JV-1–36, JV-1–38, and JV-1–42 proved to be selective for GHRH receptors, because they did not influence VIP-stimulated VPAC2 receptor-dependent prolactin release from pituitary cells or VPAC1 receptor-dependent cAMP efflux from pinealocytes but strongly inhibited GHRH-stimulated growth hormone (GH) release. Analogs JV-1–50, JV-1–51, and JV-1–52 showed various degrees of VPAC1-R and VPAC2-R antagonistic potency, although also preserving a substantial GHRH antagonistic effect. Analog JV-1–53 proved to be a highly potent VPAC1 and VPAC2 receptor antagonist, devoid of inhibitory effects on GHRH-evoked GH release. The antagonistic activity of these peptide analogs on processes mediated by receptors for GHRH and VIP was consistent with the binding affinity. The analogs with antagonistic effects on different types of receptors expressed on tumor cells could be utilized for the development of new approaches to treatment of various human cancers. PMID:10655511

  13. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    PubMed

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. PMID:26976217

  14. Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland.

    PubMed Central

    Newman, C B; Cosby, H; Friesen, H G; Feldman, M; Cooper, P; De Crescito, V; Pilon, M; Kleinberg, D L

    1987-01-01

    To determine whether the human pituitary contains a previously unidentified, nonprolactin (non-hPRL), non-growth-hormone (non-hGH) factor capable of stimulating mammary development, we tested the effects of whole human pituitary extract (hPE) and pituitary extracts depleted of hPRL and hGH ("stripped hPE") in hypophysectomized, castrated estradiol (E2)-treated male rats and rhesus monkeys. Both whole and stripped hPE significantly stimulated rat mammary development (mean scores = 3.3 and 2.0, respectively, on a scale ranging from 0 to 4) in comparison with controls (mean score = 1.0). Mammary development was not due to minute concentrations of hGH or hPRL remaining in stripped hPE because 30- to 100-fold higher concentrations of hGH (Genentech) and 1000-fold higher concentrations of hPRL were required to stimulate significant mammary development. Non-pituitary extracts of human ovary, muscle, and serum, and bovine serum albumin did not stimulate rat mammary gland growth. Trypsin destroyed the mammary mitogenic activity of whole hPE, indicating that the unidentified factor is likely a protein. Mammary growth and development were also stimulated in hypophysectomized, E2-treated monkeys by stripped hPE (mean histological score = 3.25 vs. 1.35 in control animals). Monkeys receiving stripped hPE had undetectable levels of hGH and hPRL in serum sampled over a 24-hr period. These findings suggest that the human pituitary contains a non-hPRL, non-hGH factor that stimulates mammary growth and may be important in normal mammary growth and development and perhaps in breast cancer. Images PMID:3479780

  15. Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature

    PubMed Central

    Kim, Ho-Seong; Yang, Sei Won; Yoo, Han-Wook; Suh, Byung Kyu; Ko, Cheol Woo; Chung, Woo Yeong; Lee, Kee Hyoung; Hwang, Jin Soon; Ji, Hyi-Jeong; Ahn, Hyunji

    2014-01-01

    Purpose It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin®) effect on growth promotion and safety after short-term GH treatment. Materials and Methods This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment. Results After 26 weeks of GH treatment, the height velocity significantly increased by 6.36±3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57±0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed. Conclusion This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile. PMID:24339287

  16. Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid.

    PubMed

    Ortoft, G; Oxlund, H

    1996-06-01

    A serious side effect of glucocorticoid treatment is the development of osteoporosis. We have earlier shown that long-term glucocorticoid administration results in a decrease in longitudinal bone growth, cortical bone mass, and biomechanical strength, while growth hormone administration increases these parameters. The result of biomechanical testing also indicates that glucocorticoid administration reduces the quality of bone. The glucocorticoid-induced osteopenia could not be inhibited by concomitant administration of large doses of growth hormone. The aim of the present study was to evaluate why glucocorticoid administration decreases the quality of cortical bone and why growth hormone administration had no beneficial effect on glucocorticoid-induced osteopenia. Five groups of female rats (3 1/2 months old) were treated for 80 days as follows: (1) glucocorticoid (prednisolone: Delcortol 5 mg/kg/day); (2) glucocorticoid and growth hormone; (3) saline; (4) growth hormone (recombinant human growth hormone 5 mg/kg/day); (5) Food restriction (consisting of restricted access to food to reduce their weight gain to match with that of the glucocorticoid injected rats). The animals were injected with tetracycline (15 mg/kg), 18 and 3 days before sacrifice, respectively. Furthermore, a baseline group (3 1/2-month-old female rats) was examined in order to enable us to differentiate between age-related changes and changes due to the hormone administration. Cortical mid-diaphysial cross sections of the femora were prepared and used for histological examination including determination of bone porosity, bone formation rate, and determination of the area of endosteal cavities as an indication of bone resorption. Furthermore, a cortical bone cylinder was cut from the mid-diaphysis and used for examinations of wet weight, dry weight, ash weight, volume, collagen content, and apparent density. Glucocorticoid administration resulted in an almost complete arrest of bone formation as

  17. Aspartame and its constituent amino acids: effects on prolactin, cortisol, growth hormone, insulin, and glucose in normal humans.

    PubMed

    Carlson, H E; Shah, J H

    1989-03-01

    Because large doses of phenylalanine stimulate prolactin secretion in man, we studied the acute effects of oral doses of aspartame (0.534 g, equivalent to the amount of aspartame in approximately 1 L beverage), aspartic acid (0.242 g), and phenylalanine (0.3 and 1.0 g) on serum prolactin and other hormones in normal humans. Prolactin was not stimulated by any of the aspartame meals, aspartic acid, or 0.3 g phenylalanine; a small rise in serum prolactin, similar to that produced by a high-protein mixed meal, followed ingestion of 1.0 g phenylalanine. Serum growth hormone showed no statistically significant changes in response to any of the experimental meals whereas cortisol and insulin fell slightly and glucose rose slightly during each of the meals. We conclude that these doses of aspartame do not alter secretion of prolactin, cortisol, growth hormone, or insulin in normal individuals. PMID:2923074

  18. Growth Hormone Induces Transforming Growth Factor-Beta-Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria.

    PubMed

    Chitra, P Swathi; Swathi, T; Sahay, Rakesh; Reddy, G Bhanuprakash; Menon, Ram K; Kumar, P Anil

    2015-09-01

    The glomerular podocytes form a major size selective barrier for the filtration of serum proteins and reduced podocyte number is a critical event in the pathogenesis of proteinuria during diabetic nephropathy (DN). An elevated level of growth hormone (GH) is implicated as a causative factor in the development of nephropathy in patients with type 1 diabetes mellitus. We have previously shown that podocytes express GH receptor and are a target for GH action. To elucidate the molecular basis for the effects of GH on podocyte depletion, we conducted PCR-array analyses for extracellular matrix and adhesion molecules in podocytes. Our studies reveal that GH increases expression of a gene that encodes transforming growth factor-beta-induced protein (TGFBIp) expression. Similarly, microarray data retrieved from the Nephromine database revealed elevation of TGFBIp in patients with DN. Treatment with GH results in increased secretion of extracellular TGFBIp by podocytes. Both GH and TGFBIp induced apoptosis and epithelial mesenchymal transition (EMT) of podocytes. Exposure of podocytes to GH and TGFBIp resulted in increased migration of cells and altered podocyte permeability to albumin across podocyte monolayer. Administration of GH to rats induced EMT and apoptosis in the glomerular fraction of the kidney. Therefore, we conclude that the GH-dependent increase in TGFBIp in the podocyte is one of the mechanisms responsible for podocyte depletion in DN. PMID:25740786

  19. Cognitive, Emotional, Physical and Social Effects of Growth Hormone Treatment in Adults with Prader-Willi Syndrome

    ERIC Educational Resources Information Center

    Hoybye, C; Thoren, M.; Bohm, B.

    2005-01-01

    Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of…

  20. Effect of maternal stress on the stress hormone and growth response of pigs to a lipopolysaccharide (LPS) challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study assessed the effect of maternal stress on the stress hormone and growth response of the progeny following an endotoxin challenge. Sows were assigned to one of two treatments (n = 10 per treatment) and subjected to either a daily 5-min restraint stress (stressed; S) from d 84 to d 112 of g...