Dissociation of the Disappearance of Bioactive and Radioimmunoreactive ACTH from Plasma in Man

Besser, Michael; Orth, David N.; Nicholson, Wendell E.; Byyny, Richard L.; Abe, Kaoru; Woodham, J.P.

doi:10.1210/jcem-32-5-595

Cited by 122 publications

(53 citation statements)

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“…The disappearance of ACTH from the circulation is rapid, with a circulating half-life dependent on assay methodology. By bioassay, this is 8-14 min, 5 but immunoassays suggest both shorter 6 or longer 7 clearance times.…”

Section: Bioactivity and Half-lifementioning

confidence: 99%

Analytical and clinical aspects of adrenocorticotrophin determination

Talbot¹,

Kane

White

2003

Ann Clin Biochem

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Adrenocorticotrophin (ACTH) is formed from the cleavage of pro-opiomelanocortin. Measurement of plasma ACTH is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders.Prior to the development of radioimmunoassay, the bioassays employed for the determination of ACTH were highly complex, time-consuming and costly in terms of number of animals used. Their sensitivity was such that the normal early morning peak of ACTH could not be determined. The introduction of immunoassay methodology enabled the measurement of low normal ACTH concentrations. Immunological recognition of ACTH by the antibodies employed offered improvements with regard to speci city. The development of two-site immunometric assays further improved speci city and the ability to measure low normal ACTH concentrations without the need to extract large volumes of plasma. The quanti cation of ACTH is now routinely performed in clinical laboratories, with nonradioisotopic methods becoming increasingly popular.ACTH measurement is of limited value in distinguishing between the causes of Cushing's syndrome, as there is considerable overlap in circulating ACTH concentrations in subjects with either a pituitary or an ectopic tumour. The role of ACTH precursor and related peptides in normal and pathological states and the clinical utility of their measurement remain to be fully elucidated. However, there is evidence that measurement of ACTH precursors can be a useful diagnostic tool in identifying the aetiology of Cushing's syndrome. This review will primarily address methodological aspects of ACTH measurement in the diagnosis of clinical conditions. Ann Clin Biochem 2003; 40: 453-471 Structure and nomenclature of ACTH and its related peptidesAdrenocorticotrophin (ACTH) and related peptides are derived by selective proteolytic cleavage of a common glycoprotein called pro-opiomelanocortin (POMC; MW 32 000) (see Fig. 1). Within human pituitary corticotrophs, POMC is cleaved by the enzyme prohormone convertase 1 (PC1) into an N-terminal terminal glycopeptide (N-POC, 76 aa), joining peptide (JP, 30 aa), ACTH (39 aa) and a C-terminal fragment called b-lipotrophin (bLPH, 89 aa). There is no further processing in the adult human pituitary and therefore the ACTH-related peptides in the circulation are N-POC, JP, ACTH and bLPH. However, in addition, the ACTH precursors POMC and pro-ACTH are present in the human circulation at concentrations of 5-40 pmol/L, which is ¢ve-fold greater than that of ACTH (54.1-51.4 ng/L, 50.9-11.3 pmol/L) (see Fig. 2). 1 ACTH concentrations are lower than those of N-POC (5.6-16.8 pmol/ L) and approximately equimolar with those of bLPH (2.5-6.7 pmol/L). However, b-endorphin concentrations (41.7 pmol/ L) are consistently lower than those of the other peptides. Further processing can occur in animals that have neurointermediate lobes in the pituitary. These cells contain prohormone convertase 2 (PC2), which can cleave ACTH to a-melanocyte-stimulating hormone (aMSH, 13 aa) and corticotrophin-like intermediat...

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Section: Bioactivity and Half-lifementioning

confidence: 99%

Analytical and clinical aspects of adrenocorticotrophin determination

Talbot¹,

Kane

White

2003

Ann Clin Biochem

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“…ACTH appears to be degraded both in circulating blood and in tissues by the action of proteolytic enzymes that cleave the molecule first in its N-terminal sequence, thus destroying its steroidogenic activity, and subsequently in its C-terminal portions (White & Gross, 1957;Imura et a/., 1967;Besser et al, 1971a). Therefore it might be expected that ACTH biological activity would disappear faster from blood than immunological reactivity, that bioactive ACTH levels in plasma would be lower than immunoreactive levels and that, in turn, N-terminally reactive ACTH levels would be lower than C-terminally reactive ACTH.…”

Section: Relationship Of Immunoassay Results To Bioactivitymentioning

confidence: 99%

“…This had led to some confusion since it has not always been fully explained in the published papers. An example of this is given in the assessment of the potency of the highly purified human ACTH of Lerner, Upton & Lande (preparation 8B), which was reported by Besser et al (1971a) as 101 5 19.0 (S.D.) units per mg, using the intravenous Lipscomb-Nelson assay.…”

Section: S T a N D A R D S F O R A C T H Assay Bioassaymentioning

confidence: 99%

Acth and MSH Assays and Their Clinical Application

Besser

1973

Clinical Endocrinology

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“…In more dynamic situations, in which the hormone levels rise rapidly and fall quickly, as in the insulin hypoglycaemia test in vivo, differences between radioimmunoassay and the cytochemical bioassay became apparent during the period when the levels were falling (Fleisher, Glass, Bitensky, Chayen & Daly, 1974). This would reflect the longer half-life of the hormone, as measured by the radioimmunoassay which was still detecting biologically inactive fragments (Besser et al, 1971).…”

Section: Validity Of the Cytochemical Bioassaysmentioning

confidence: 99%

“…For example, there was no point in raising an antibody to the a-subunit of FSH since that antibody would cross-react with all glyco¬ protein hormones which have the common subunit. Equally, it was inadvisable to use an antibody to the C-terminal amino acids of ACTH when the biological activity resided in the N-terminal part; the former could give erroneous values for biological activity (as discussed by Besser et al, 1971).…”

Section: Introductionmentioning

confidence: 99%

Cytochemical bioassays of polypeptide hormones

Bitensky¹

1977

Reproduction

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Dissociation of the Disappearance of Bioactive and Radioimmunoreactive ACTH from Plasma in Man

Cited by 122 publications

References 0 publications

Analytical and clinical aspects of adrenocorticotrophin determination

Analytical and clinical aspects of adrenocorticotrophin determination

Acth and MSH Assays and Their Clinical Application

Cytochemical bioassays of polypeptide hormones

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