Circulating human pituitary pro-γ-melanotropin enhances the adrenal response to ACTH

Al-Dujaili, Emad A S; Hope, J.; Estivariz, Fernando E.; Lowry, P. J.; Edwards, C. R. W.

doi:10.1038/291156a0

Cited by 144 publications

(34 citation statements)

References 13 publications

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“…The modulatory effects of pro-opiomelanocortin (POMC) products other than ACTH, particularly with reference to the N-terminal region, have been investigated by a number of workers, but with conflicting results. Although N-POMC has been shown to have a mild to moderate potentiating effect by some workers , Al-Dujaili et al 1981, such actions have not been confirmed by other studies (Pham-Huu-Trung et al 1982, Cathiard et al 1985.…”

Section: Introductionmentioning

confidence: 72%

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

Jenkins¹,

Cross²,

Perry³

et al. 1999

Journal of Endocrinology

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Early descriptions of in vitro ACTH bioassays all emphasised the need to use extracted plasma samples due to interference by an unidentified component. The aim of these studies was to elucidate the effects of whole plasma on ACTH steroidogenic activity in vitro and to identify the responsible factor. A sensitive in vitro dispersed bovine adrenocortical cell bioassay was established. The addition of 10% ACTH-depleted human pooled plasma to the incubation media resulted in basal steroidogenesis equivalent to that achieved with 10 9 M ACTH 1-24 and potentiated the steroidogenic activity of 10 9 M ACTH 1-24 by 7·8-fold. This potentiation was dependent on the concentration of both ACTH and plasma in the media, but did not result from the mitogenic effect of plasma. A pituitary source was excluded and the potentiating activity was not extractable by Vycor glass. Column chromatography demonstrated two peaks of activity corresponding to molecular weights of 650 and 220 10 3 Da. These peaks did not correspond to the plasma binding of 125 I-ACTH which resulted from non-specific binding to albumin. Lipoprotein-deficient serum had no effect on either basal or ACTH-stimulated steroidogenesis, but both were restored by the addition of purified lipoproteins. However, novel findings demonstrated a differential effect of low (LDL) and high (HDL) density lipoproteins on basal and ACTH-stimulated steroid production; thus, LDL exerted a greater effect on the former, whilst HDL potentiated the steroidogenic activity of added ACTH more than LDL. The addition of the lipoproteins to lipoprotein-deficient serum restored its basal and ACTH potentiating effects, the cholesterol concentrations of the chromatographic fractions exactly paralleling their ACTH potentiating effect. These findings suggest that not only are lipoproteins the plasma factor(s) which potentiates ACTH steroidogenic activity in in vitro bioassays, but also that they exert differential effects on basal and ACTH-stimulated steroid production.

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Section: Introductionmentioning

confidence: 72%

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

Jenkins¹,

Cross²,

Perry³

et al. 1999

Journal of Endocrinology

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“…When added alone to adrenal cells in vitro, it did not cause steroidogenesis but did promote RNA synthesis (Al Dujaili et al 1982). It also potentiated the steroidogenic activity of ACTH several-fold in perfused rat adrenal cells in vitro (Al Dujaili et al 1981). This potentiation was completely abolished in the presence of actinomycin D, indicating that the increase in RNA synthesis was linked to the potentiating activity of pro-γ-MSH (Al Dujaili et al 1982).…”

Section: Isolation and Characterisation Of Human Pro-γ-mshmentioning

confidence: 86%

60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins

Lowry

2016

Journal of Molecular Endocrinology

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The remarkable conservation of the primary structures and anatomical location of dogfish α-melanocyte-stimulating hormone (MSH), corticotrophin-like intermediate lobe peptide (CLIP) and adrenocorticotrophic hormone (ACTH) compared with mammals reinforced the tissue-specific processing hypothesis of ACTH peptides in the pituitary gland. The cloning of dogfish pro-opiomelanocortin (POMC) led to the identification of δ-MSH and simultaneously revealed the high conservation of the γ-MSH sequence during evolution. These studies have also shown that β-MSH is much less conserved during evolution and in some species is not even processed from β-LPH. Human pro-γ-MSH potentiates the corticosteroidogenic activity of ACTH and peptides generated from its N-terminal, in particular big-γ-MSH, appear to have adrenal mitogenic activity. Human big-γ-MSH (from the zona intermedia) may also cause the adrenache. The review finishes with a cautionary note with regard to the misdiagnosis of the ectopic ACTH syndrome in which partial processing of ACTH can result in large concentrations of α-MSH and CLIP, which can interfere in the performance of two-site immunoassays, and the problem of the correct disulphide bridge arrangement in synthetic N-POMC peptides is also discussed.

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“…The first reports for a role for these peptides appeared in the early 1980s (for a review see Harmer and Bicknell, 2005) when it was demonstrated that Lys-γ3-MSH and pro-γ-MSH, although not directly steroidogenic, have the ability both in vitro and in vivo to potentiate the steroidogenic response of the rat adrenal to ACTH (Figure 2) , Al-Dujaili et al 1981. This effect appears to correlate with the ability of both peptides to increase the activity of the enzyme Hormone Sensitive Lipase (HSL) .…”

Section: The Biological Role Of Gamma-mshmentioning

confidence: 99%

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

Bicknell

Harmer²,

Yiangson³

et al. 2009

Molecular and Cellular Endocrinology

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Circulating human pituitary pro-γ-melanotropin enhances the adrenal response to ACTH

Cited by 144 publications

References 13 publications

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

The influence of plasma on basal and ACTH-stimulated in vitro adrenocortical steroidogenesis

60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins

Lys-gamma3-MSH: A global regulator of hormone sensitive lipase activity?

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