Plasma “Big” and “Big-Big” Growth Hormone (GH) in Man: An Oligomeric Series Composed of Structurally Diverse GH Monomers*

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

doi:10.1210/jcem-59-2-212

Cited by 89 publications

(34 citation statements)

References 24 publications

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“…A weak negative linear correlation (r = -0.526) was observed between GH binding and GH content of these sera (Fig. 6) (7,8,18). In our studies, a mini-gel filtration system ald not be ac-(Ultrogel AcA44, 0.6 X 22 cm) has been used to achieve an ,erum (<2 ng/ appropriately rapid, simple, quantitative, and discriminatory ).005) in three separation.…”

Section: Resultsmentioning

confidence: 59%

“…The possibilities considered were that they represented hGH precursors, hGH aggregates (either random or formal polymers, including disulfide-linked forms), hGH bound to one or more serum proteins or immunoassay artifacts. The most widely held view has been that they are hGH aggregates and this was recently supported by a detailed investigation by Stolar et al (18) who deduced that big GH was an hGH dimer and big-big GH was a mixture of tri-, tetra-, and pentamers. Although it appeared that unlabeled hGH, when incubated with plasma (1 h, 22°C) did not appreciably change its molecular size (as determined by radioimmunoassay of fractions from Sephadex G-100 gel filtration), close inspection of their data indicates that one cannot rule out the possibility that GH binding to one or more plasma proteins, as opposed to simple aggregation, would be a sufficient and satisfactory explanation for the size heterogeneity.…”

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

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

Herington¹,

Ymer²,

Stevenson³

1986

J. Clin. Invest.

327

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Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 94%

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

Herington¹,

Ymer²,

Stevenson³

1986

J. Clin. Invest.

327

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“…20,21 It is currently known that the GH receptor antibodies are most likely so called "Big-Big" GH. But, in that case, the patient must have an active GH secreting tumour, even though the serum GH levels may be normal.…”

Section: Discussionmentioning

confidence: 99%

Acromegaly with Normal Basal Growth Hormone Levels

Mohr

Chen²,

Schweitzer

1997

Can. j. neurol. sci.

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Background: The most common cause of acromegaly is excess of growth hormone (GH) secretion. Methods: We report a 42-year-old male patient, who had become acromegalic over the past 5 years. There were no visual changes or change in sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and extending into and totally filling up the sphenoid sinus with diffusely invasive features. Results: Basal serum GH level was within normal range, but insulin-like growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and impaired GH secretory regulation as well. A pituitary adenoma was partially removed through transsphenoidal microsurgery. Pathology confirmed a mammo-somatotrophic adenoma but immunocytochemistry study of the tumour showed only positivity for PRL but not GH. Conclusions: When acromegaly occurs without GH level elevation, one should pay attention that: 1) IGF-1 might be the cause of the clinical feature of acromegaly; 2) The tumour might undergo morphological transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could also be the cause of the acromegalic appearance. RESUME: Acromegalic avec niveau normal d'hormone de croissance: a propos d'un cas. Introduction: La cause la plus commune de l'acromfigalie est l'exces de secretion d'hormone de croissance (GH). Methodes: Nous rapportons le cas d'un patient de 42 ans qui etait devenu acromegale depuis les cinq dernieres ann6es. II n'y avait aucune modification de la vision ni des fonctions sexuelles, aucune gyn£comastie ni galactorrhea. La tomodensitometrie et l'imagerie par resonnance magnetique (IRM) ont montre une volumineuse masse a caracteres invasifs diffus, mesurant 2.5 x 2.5 x 3.5 cm, prenant origine au niveau de la selle turcique et remplissant completement le sinus sphenoidal. Resultats: Le niveau serique basal de GH etait normal, mais le niveau du factor de croissance 1 de genre insulinique (IGF-1) 6tait Sieve avec une legere elevation de la prolactine (PRL) et une alteration dans la regulation de la secretion de GH. Un ad6nome hypophysaire fut partiellement reseque par microchirurgie transspheWidale. L'examen anatomopathologique a confirme qu'il s'agiasait d'un adenome mammo-somatotrophe mais l'examen immunohistochimique de la tumeur n'a montre de positivit6 que pour la PRL, mais non pour la GH. Conclusions: Lorsqu'il y a symptomes d'acromegalie sans elevation de GH, on devrait se demander si: 1) l'IGF-1 peut etre la cause des signes d'acrom6galie; 2) la tumeur pourrait subir une transformation morphologique; et 3) une hyperinsulinemie ou la formation d'anticorps diriges contre le r6cepteur GH pourraient etre la cause des signes d'acromegalie.Can. J. Neurol. Sci. 1997; 24: 250-253 Acromegaly was first recognized as a distinct clinical syndrome by Marie in 1886.' The pituitary source of the disorder was confirmed in 1909 by Cushing.2 Now, it has been generally recognized as the result of an unrestra...

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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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Plasma “Big” and “Big-Big” Growth Hormone (GH) in Man: An Oligomeric Series Composed of Structurally Diverse GH Monomers*

Cited by 89 publications

References 24 publications

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

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

Acromegaly with Normal Basal Growth Hormone Levels

Circulating Molecular Variants of Growth Hormone in Childhood

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