Regional Distribution of Pro-Opiomelanocortin-Derived Peptides in the Human Brain

Emson, P.C.; Corder, Roger; Sj, Ratter; Tomlin, Susan; Lowry, P. J.; Lh, Ress; Arregui, Alberto; Mn, Rosser

doi:10.1159/000123864

Cited by 29 publications

(5 citation statements)

References 31 publications

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“…Pro-opiomelanocortin (POMC) is the precursor peptide for ACTH, p-endorphin, 8and y-lipotrophins, and a-, pand y-melanocyte-stimulating hormones. These peptide products have been demonstrated immunohistochemically in several extrapituitary, non-tumorous tissues (Tanaka et al, 1982;Nicholson et al, 1987;Bruni et al, 1979;Emson et al, 1984;Liotta et al, 1977;Texier et al, 1991). Various POMC transcript sizes have been identified at the RNA level.…”

Section: Discussionmentioning

confidence: 99%

Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

O’Brien

Young

Davlla³

et al. 1992

Clinical Endocrinology

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We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.

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Section: Discussionmentioning

confidence: 99%

Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

O’Brien

Young

Davlla³

et al. 1992

Clinical Endocrinology

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“…The dried sample is then reconstituted in 0.01 M HCl and diluted in appropriate assay bu¡er. 62 Alternatively, the lyophilized supernatant is resuspended in tri£uoroacetic acid (0.1%) and further puri¢ed on C18 Sep-Pak cartridges (Waters Associates, Millford, MA, USA). 61 …”

Section: Specimen Requirements Sample Timing and Handlingmentioning

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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“…Its distribution is similar to that of the rat and other mammals (23,24) and, like the rat, most of the immunoreactive R-endorphin in human brain is localized within neuronal processes which arise from cell bodies in the medial basal hypothalamus (25).…”

Section: The Regulation Of B-endorphin Processing In Rat Brainmentioning

confidence: 61%

The Regulation of a Post-Translational Peptide Acetyltransferase: Strategies for Selectively Modifying the Biological Activity of Neural and Endocrine Peptides

Millington¹

1991

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Regional Distribution of Pro-Opiomelanocortin-Derived Peptides in the Human Brain

Cited by 29 publications

References 31 publications

Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

Cushing's syndrome associated with ectopic production of corticotrophin‐releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

Analytical and clinical aspects of adrenocorticotrophin determination

The Regulation of a Post-Translational Peptide Acetyltransferase: Strategies for Selectively Modifying the Biological Activity of Neural and Endocrine Peptides

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