Molecular Forms of Circulating Growth Hormone during Spontaneous Secretory Episodes and in the Basal State*

Baumann, Gerhard; Stolar, Mark W.; Amburn, Klaus

doi:10.1210/jcem-60-6-1216

Cited by 87 publications

(31 citation statements)

References 24 publications

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“…Preliminary data from these 20K-specific assays have confirmed earlier conclusions, from physico-chemical separation, about the proportion of 20K in the circulation [8, 9, 10, 11]. Both 20K and 22K GH appear to be co-secreted in a fixed proportion, and no stimuli favoring secretion of one form versus the other have been identified [8, 9, 10, 11]. …”

Section: Monomeric Human Gh Variantssupporting

confidence: 73%

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Growth Hormone Heterogeneity in Human Pituitary and Plasma

Baumann¹

1999

Horm Res Paediatr

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Several isoforms of growth hormone (GH) have been identified in humans. There are many reasons for this heterogeneity. At the genetic level, two genes encode GH: GH-N, expressed in the pituitary, and GH-V, expressed in the placenta. At the mRNA level, GH-N undergoes alternative splicing into 20K and 22K isoforms. Post-translationally, 22K GH undergoes modifications, such as acetylation at its amino terminus, deamidation, and oligomerization. The picture is complicated further in the circulation, where GH binds to two GH-binding proteins, each with different affinities for the GH isoforms. In addition, a highly heterogeneous mixture of GH fragments has been demonstrated. The implications of this heterogeneity relate to differences between GH immunoassays, such that assay results cannot be compared between laboratories. The reasons for GH heterogeneity and its practical and clinical implications are considered here.

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Section: Monomeric Human Gh Variantssupporting

confidence: 73%

“…Immunoreactive species that may represent GH fragments have been demonstrated in plasma [10]. This is a highly heterogeneous mixture that varies between plasma samples.…”

Section: Gh Fragments and Degradation Productsmentioning

confidence: 99%

Growth Hormone Heterogeneity in Human Pituitary and Plasma

Baumann¹

1999

Horm Res Paediatr

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“…CIRCULATING human growth hormone (hGH) consists of several molecular isoforms, in which 22 kilodalton hGH (22K-hGH) is the most abundant [1]. Twenty kilodalton human GH (20K-hGH), a naturally occurring isoform of 22K-hGH, arises from the same gene (hGH-N) as 22K-hGH by alternative splicing of mRNA [2].…”

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confidence: 99%

Serum Levels of 20 Kilodalton Human Growth Hormone (20K-hGH) in Patients with Acromegaly before and after Treatment with Octreotide and Transsphenoidal Surgery

et al. 2004

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Abstract. Circulating human GH (hGH) consists of several molecular isoforms. It was previously reported that the proportion of 20 kilodalton hGH (20K-hGH) was elevated in the serum of patients with active acromegaly. In this study, we investigated the effects of octreotide and transsphenoidal adenomectomy on the proportion of 20K-hGH in the serum of 7 acromegalic patients. To achieve an acute effect, octreotide (100 mg) was subcutaneously injected as a bolus. To observe the chronic effects of octreotide therapy and surgery, serum samples were obtained by repetitive blood sampling before and 3 to 8 weeks after treatment. Serum levels of 20K-hGH and 22 kilodalton hGH (22K-hGH) were determined by specific enzyme-linked immunosorbent assay. A bolus injection of octreotide elicited a parallel decrease in serum 22K-hGH and 20K-hGH, resulting in an unchanged proportion of 20K-hGH to total circulating hGH. The proportion of 20K-hGH was decreased in 4 of 4 patients 4 to 7 weeks after surgery and in 2 of 4 patients after chronic treatment with octreotide for 3 to 8 weeks. The proportion of serum 20K-hGH was positively related to mean serum 20K-hGH as well as serum total hGH levels, but not with serum IGF-I levels. These findings suggest that high serum levels of 20K-hGH or total hGH per se might elicit a chronic change in the clearance kinetics of 20K-hGH and increase the proportion of 20K-hGH in acromegalic patients.

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“…Recent by PAGE under nondenaturing conditions at pH 7.5 in a disconevidence has shown that in adult man, at least three monomeric tinuous TES-acetate-chloride-Bistris buffer system. Experimental species and several hGH oligomers circulate in blood (3)(4)(5)(6)(7). The details of these procedures have been reported previously (3,15).…”

Section: Page Polyacrylamide Gel Electrophoresismentioning

confidence: 99%

Circulating Molecular Variants of Growth Hormone in Childhood

1987

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ABSTRACT. Human growth hormone (hGH) is known to "bioinactive hGH" as a basis for growth failure (13,14). Recent consist of several molecular forms. We examined the mo-improvements in the sensitivity of analytical techniques have lecular nature of circulating hGH in 18 normal children made it possible to achieve that goal. and compared the resulting patterns to those previously obtained in adults. hGH secretion was stimulated with L-MATERIALS A N D METHODS dopa, the hormonal forms were extracted from plasma by hmunoadsorbent chromatography, and their molecular Subjects. Eighteen prepubertal children, aged 6-1 3 yr, particnature was analyzed by polyacrylamide gel electrophoresis. ipated in the study. Eleven were boys and seven were girls. All Circulating monomeric hGH consisted of 73% hGH22~, underwent a standard L-dopa test (500 mg/m2) and blood was 16% hGH20~, and 10% of an acidic hGH from (N,-acylated drawn at 30. 60, and 90 min after administration of the secretaor deamidated hGH). These relative proportions are indis-gogue. The tests were performed as part of the diagnostic procetinguishable from those found in the plasma of adults. No dures for short stature. All children had normal growth age or sex differences in the circulating hGH Pattern were velocity. Ethical considerations prompted us to perform pharfound. We conclude that the types and proportions of hGH macological testing and venipunctures only in children where a forms in the blood of normal children are the same as those medical indication existed. Following full diagnostic work-up, all previously established in adults. These data provide a children were found to have normal endocrine function and no framework against which children with postulated struc-identifiable disease. The subsequent clinical course over a 2-yr turally abnormal ("bioinactive") hGH can be compared. period confirmed this assessment. All children had peak hGH (Pediatr Res 22: 21 -22, 1987) responses exceeding 7 ng/ml (range 9.7-35.6 ng/ml) after Ldopa. Blood samples obtained at the time of spontaneous elevaAbbreviations tion of hGH in two children were also included. The procedures had been approved by the Institutional Review Boards for HuhGH, human growth hormone man Experimentation at both participating institutions. PAGE, polyacrylamide gel electrophoresisAnalysis. Plasma from one to three time points was pooled to SDS, sodium dodecyl sulfate yield a minimum quantity of hGH of 20 ng (range 20-108 ng). hGH and all its variants were then extracted from plasma by immunoadsorbent chromatography as described in detail previously (3). The extracted hGH was analyzed for molecular variants hGH consists of several distinct moIecuIar forms (1,2). Recent by PAGE under nondenaturing conditions at pH 7.5 in a disconevidence has shown that in adult man, at least three monomeric tinuous TES-acetate-chloride-Bistris buffer system. Experimental species and several hGH oligomers circulate in blood (3-7). The details of these procedures have been reported previously (3, 15). three ~G H m...

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Molecular Forms of Circulating Growth Hormone during Spontaneous Secretory Episodes and in the Basal State*

Cited by 87 publications

References 24 publications

Growth Hormone Heterogeneity in Human Pituitary and Plasma

Growth Hormone Heterogeneity in Human Pituitary and Plasma

Serum Levels of 20 Kilodalton Human Growth Hormone (20K-hGH) in Patients with Acromegaly before and after Treatment with Octreotide and Transsphenoidal Surgery

Circulating Molecular Variants of Growth Hormone in Childhood

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