Molecular Forms of Human Growth Hormone Secreted in Vivo: Nonspecificity of Secretory Stimuli*

Baumann, Gerhard; Stolar, Mark W.

doi:10.1210/jcem-62-4-789

Cited by 57 publications

(40 citation statements)

References 9 publications

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“…Confirming the results reported by others using SDS-PAGE [5,6,16] or the 22K GH exclusion assay [7], there was no significant difference in the ratio of 20K to 20K plus 22K hGH between before and after these provocative tests (Fig. 2), suggesting that secretion of both species of The ratio of 20K hGH to 20K plus 22K hGH was determined in active acromegaly (ACR; N=34), inactive acromegaly (IAC; N=10), untreated Graves' disease (GR; N=9), primary hypothyroidism (HT; N=10), anorexia nervosa (AN; N=8), idiopathic short stature (ISS; N=9), GH deficiency (GHD; N=31), chronic renal failure (CRF; N= 10), diabetes mellitus (DM; N=11), and prolactinoma (PRO; N=5).…”

Section: Resultssupporting

confidence: 88%

“…Despite these studies, little information is available on the proportion of 20K hGH isoform in circulation under different physiological and pathophysiological conditions because of the lack of a specific assay. Serum concentrations of 20K hGH or non-22K hGH have been determined by several methods [5][6][7][8]. However, these methods require several steps and are not suitable for determining serum concentrations of the 20K hGH in a large number of samples.…”

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confidence: 99%

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Serum Concentrations of 20K Human Growth Hormone in Normal Adults and Patients with Various Endocrine Disorders

et al. 2000

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Abstract.The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary.The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 ± 178 pg/mL (N = 282) in normal women, significantly higher than in normal men (64± 170 pg/mL, N=226).However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 ±2.6%, N= 176) and women (6.3±2.1 0, N=263).No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P<0.001) higher in patients with active acromegaly (9.2±2.2%, N = 33) and in patients with anorexia nervosa (9.0± 1.9, N = 8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH.The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH. THERE are several isoforms of human growth hormone (27K, 22K, 20K, and 19K hGH, and 5K hGH fragment) in both pituitary and serum [1] . The major species is 22K hGH, and the second most abundant isoform is 20K hGH, which lacks 32-46 residues of 22K hGH. The 20K hGH is produced by alternative splicing of 22K hGH mRNA [2],and this

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Section: Resultssupporting

confidence: 88%

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confidence: 99%

Serum Concentrations of 20K Human Growth Hormone in Normal Adults and Patients with Various Endocrine Disorders

et al. 2000

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“…A produção hipofisária de GH advém da expressão exclusiva do gene hGH-N, o qual origina uma proteína de peso molecular de 22 kDa, constituída por 191 aminoácidos e representa cerca de 90% do GH hipofisário (3,11). Aproximadamente 10% do GH presente na hipófise corresponde à variante molecular de 20 kDa, que é resultado da perda de 15 aminoácidos (splicing) presentes na forma 22 kDa.…”

Section: Hormônio Do Crescimentounclassified

“…Já a GHBP-2 apresenta baixa afinidade de ligação, mas grande capacidade, e não fica saturada com níveis séricos elevados de GH. Não se conhece o mecanismo exato pelo qual isso ocorre (10,11).…”

Section: Hormônio Do Crescimentounclassified

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Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

Casagrande

Czepielewski

2007

Arq Bras Endocrinol Metab

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RESUMOA dosagem do GH no soro é essencial para confirmar ou excluir o seu excesso. Na acromegalia, a ausência de critérios clínicos suficientemente sensíveis para monitorizar o sucesso do tratamento faz com que o GH sérico seja o procedimento de escolha e, para isso, é essencial que a sua dosagem seja realizada de forma confiável, capaz de permitir interpretações uniformes. Vários critérios hormonais têm sido propostos para caracterizar remissão da acromegalia, incluindo níveis séricos de GH randômico inferior a 2,5 µg/l, nadir de GH durante o teste de tolerância oral a glicose inferior a 1,0 µg/l e IGF-I normal para sexo e idade. A importância do tratamento adequado consiste na possibilidade de reverter a mortalidade prematura da acromegalia através da diminuição dos níveis de GH para valores menores que 2,5 µg/l. Com o surgimento de ensaios ultra-sensíveis para medida do GH, tornaram-se necessários critérios mais estritos para determinar cura ou remissão da doença. Nesta revisão, descreveremos aqui as modificações decorrentes da evolução dos ensaios, as conseqüências nos resultados de GH e os pontos de corte propostos na literatura para caracterização da atividade e remissão da acromegalia. ABSTRACT Growth Hormone (GH) and IGF-I Assays: Methodological Aspects and its Implications in Acromegaly Diagnosis and Follow-Up.Growth hormone quantification in serum is essential for confirming or ruling out its excess. The absence of clinical criteria sufficiently sensitive to evaluate the treatment success enables GH as the key diagnostic procedure and for that, its measurements must be done in a reliable way and must allow uniform interpretation. Several different biochemical criteria for remission have been suggested in the past, including a random GH measurement less than 2.5 µg/l, mean GH value from a day curve less than 2.5 µg/l, nadir GH value after an oral glucose tolerance test (OGGT) less than 1.0 µg/l and a normal age-related IGF-I level. The importance of adequate treatment is highlighted by data indicating that lowering GH levels to less than 2.5 µg/l reverses the premature mortality of acromegaly. With the advances of ultrasensitive assays for GH measurement, strictest remission criteria to determine remission or cure were necessary. In this review, we describe the changes of assay methodology and its consequences in serum GH results and cut off point values to define activity and remission of acromegaly.

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Development of a Bioassay System for Human Growth Hormone Determination with Close Correlation to Immunoassay

Maimaiti¹,

Tanahashi

Mohri

et al. 2012

Clinical Laboratory Analysis

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Serum growth hormone (GH) level is measured largely through immunoassays in clinical practice. However, a few cases with bioinactive and immunoreactive GH have also been reported. We describe here a new bioassay system for GH determination using the BaF/GM cell line, which proliferates in a dose-dependent manner on hGH addition; cell proliferation was blocked by anti-hGH antibody. This bioassay had the lowest detection limit (∼0.02 ng/ml) reported thus far and the highest specificity for GH. The bioassay results were compared with those of an immunoradiometric assay across 163 patient samples in various endocrine states. A close correlation (the ratio of bioactivity/immunoreactivity was 1.04 ± 0.33, mean ± SD) was observed between bioactivity and immunoreactivity in these samples. The newly developed system is a specific, sensitive, easy, and fast bioassay system for GH determination; we consider it useful for evaluating GH bioactivity in various endocrine states.

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Molecular Forms of Human Growth Hormone Secreted in Vivo: Nonspecificity of Secretory Stimuli*

Cited by 57 publications

References 9 publications

Serum Concentrations of 20K Human Growth Hormone in Normal Adults and Patients with Various Endocrine Disorders

Serum Concentrations of 20K Human Growth Hormone in Normal Adults and Patients with Various Endocrine Disorders

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

Development of a Bioassay System for Human Growth Hormone Determination with Close Correlation to Immunoassay

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