Regulation of Human Growth Hormone Secretion and Its Disorders.

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

doi:10.2169/internalmedicine.41.7

Cited by 73 publications

(55 citation statements)

References 53 publications

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“…Acidophile-derived hormones include GH and PRL. GH synthesis and secretion is tightly regulated by a number of feedback systems; several reviews [32][33][34] expound upon specific control mechanisms of endocrine GH synthesis and regulation. In short, neurons from the hypothalamus project to the pituitary where GH releasing hormone (GHRH) secretion stimulates GH gene expression and GH secretion while somatostatin (SRIF) secretion from another subset of hypothalamic neurons inhibits GH release.…”

Section: The Pituitary and Hypothalamusmentioning

confidence: 99%

GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

Gosney¹,

Jara²,

Basu

et al. 2012

TOEJ

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Various central nervous system (CNS) tissues express both growth hormone (GH) and its receptor (GHR), including those involved in memory and cognition. Studies show the presence of GHR in the pituitary, choroid plexus, hypothalamus, hippocampus, pituitary and the spinal cord during development and, to a lesser extent, in adults. This expression implies a role of GH signaling in growth, development and functionality of the CNS. While data on the function of GH in the CNS is sparse, several studies have been conducted using the GHR knockout (-/-) mouse in order to better understand this role. Abnormal growth hormone signaling in humans is the cause of various diseases that include Laron syndrome, GH deficiency and acromegaly. This article will review the research conducted using the GHR-/-mouse on the role of GH signaling in the CNS. Where possible, we will attempt to contextualize the animal data with respect to human disease.

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Section: The Pituitary and Hypothalamusmentioning

confidence: 99%

GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

Gosney¹,

Jara²,

Basu

et al. 2012

TOEJ

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“…Like all other variants, the 22 kDa-GH is produced, by proteolytic cleavage of the somatotropin precursor under the regulation by the growth hormone releasing hormone (GHRH), somatostatin, and ghrelin [17,18]. A 22 kDa-GH deficiency in humans results in dwarfism, while excess is associated with the syndrome of acromegaly [19][20][21].…”

Section: Somatotropinmentioning

confidence: 99%

Phosphoproteomic analysis of the human pituitary

et al. 2006

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The pituitary is the central endocrine gland that regulates the functions of various target organs in the human body. Because of the pivotal regulatory role of the pituitary, it is essential to define on a global scale the components of the pituitary protein machinery, including a comprehensive characterization of the post-translational modifications of the pituitary proteins. Of particular interest is the examination of the phosphorylation status of the pituitary in health and disease. Towards the goal of global profiling of pituitary protein phosphorylation, we report here the application of the in-gel IEF-LC-MS/MS approach to the study of the pituitary phosphoproteome. The analytical strategy combined isoelectric focusing in immobilized pH gradient strips with immobilized metal ion affinity chromatography and mass spectrometry. With this method, a total of 50 phosphorylation sites were characterized in 26 proteins. Because the investigation involved primary tissue, the findings provide a direct glimpse into the phosphoprotein machinery operating within the human pituitary tissue microenvironment.

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“…In corroboration, clinical studies have shown that newborns have an exaggerated response to GHRH and a delayed and blunted response to somatostatin (Delitala et al 1978, Shimano et al 1985. Postnatally, these elevated hGH levels would cause high serum levels of IGF-I and IGFBP-3, resulting in gigantism in a prepubertal child and acromegaly in an adult (Kato et al 2002). However, in the fetus, serum IGF-I and IGFBP-3 levels are very low or undetectable until late in the third trimester (Butler & Le Roith 2001, Gohlke et al 2004.…”

Section: Discussionmentioning

confidence: 93%

“…This is likely due to the greater sensitivity of the human fetal pituitary somatotrope to its hypothalamic stimulatory factor, GHreleasing hormone (GHRH), than its inhibitory factor, somatostatin, throughout in utero development (Delitala et al 1978, Goodyer et al 1993a. Similar hGH levels postnatally cause highly elevated serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3), resulting in gigantism in the prepubertal child and acromegaly in the adult (Kato et al 2002). However, circulating levels of IGF-I and IGFBP-3 in the fetus are low, reaching significant levels only late in the third trimester (Butler & Le Roith 2001, Gohlke et al 2004, suggesting a blunted responsiveness of fetal tissues to hGH during earlier stages in development, at either the hGH receptor or the signaling level.…”

Section: Introductionmentioning

confidence: 99%

Developmental changes in the human GH receptor and its signal transduction pathways

Kenth

Mergelas²,

Goodyer

2008

Journal of Endocrinology

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We previously reported the presence of functional human GH receptors (hGHRs) in the human fetal hepatocyte (FH) as early as the first trimester. Interestingly, fetal serum levels of hGH are in the acromegalic range, yet certain hGH-dependent factors are expressed at very low levels (IGF-I, IGF-binding protein-3), suggesting that fetal liver has limited responsiveness to hGH. To determine whether this is due to the fetal tissue levels of hGHR or factors in the hGH/hGHR axis that might influence hGHR function, we compared hGHR isoforms and downstream signaling proteins in FH versus human adult liver (HAL). Immunoprecipitation/immunoblotting (IB) analyses found similar precursor and mature hGHR forms while RT-PCR assays of truncated (T) hGHR 1-279 , dominant negative for the full-length (FL) receptor, showed similar T/FL mRNA ratios in FH and HAL. IB demonstrated that Janus kinase (JAK) 2, signal transducers and activators of transcription (STAT(1, 3, 5A/B)), and suppressors of cytokine signaling (SOCS(1, 2, 3, cytokineinducible SH2-containing protein (CIS))) proteins were detectable in all FH and HAL tested (12 weeks of fetal age to 60 years); the levels were similar (STAT5B) or lower (JAK2/STAT1/STAT3/STAT5A: 38-53%, SOCS/CIS: 58-76%) in FH compared with HAL. Our studies to date demonstrate that, during hepatocyte development, hGHR levels are lower in the fetal cells but the hGHR isoforms, including the relative amount of truncated versus FL, remain unchanged. The JAK2/STAT/SOCS signaling molecules are present in the FH as early as the first trimester. However, they are generally at !50% level in postnatal liver. These data suggest that low expression of both hGHR and major hGHR signaling components may explain the limited responsiveness of the fetal cells to the high circulating levels of hGH.

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Regulation of Human Growth Hormone Secretion and Its Disorders.

Cited by 73 publications

References 53 publications

GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

Phosphoproteomic analysis of the human pituitary

Developmental changes in the human GH receptor and its signal transduction pathways

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