Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension.

Griffing, George T.; Berelowitz, Brian A.; Hudson, Margo; Salzman, Robert T.; Manson, Jo Ann E.; Aurrechia, S.; Melby, James C.; Pedersen, Robert C.; Brownie, Alexander C.

doi:10.1172/jci111941

Cited by 30 publications

(13 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells can be identified in the human pituitary, however, with histochemical and immunocytochemical characteristics of melanotrophs (39,(43)(44)(45), and γ-MSH-like immunoreactivity has been identified in human plasma, although not fully characterized (46,47). Some years ago, Griffing and colleagues proposed that this peptide may be involved in the pathogenesis of some forms of idiopathic hyperaldosteronism (46). Mineralocorticoidinduced hypertension, however, does not seem to account for the salt sensitivity of PC2 -/-mice, since plasma aldosterone concentration was suppressed by the HSD in the knockouts to the same extent as in the wild-type mice.…”

Section: Discussionmentioning

confidence: 99%

Genetic disruption of γ-melanocyte–stimulating hormone signaling leads to salt-sensitive hypertension in the mouse

Ni¹,

Pearce²,

Butler³

et al. 2003

J. Clin. Invest.

View full text Add to dashboard Cite

IntroductionNumerous neural and humoral systems interact to control total body sodium content, body fluid volumes, and blood pressure through the regulation of urinary sodium excretion (U Na V). These include antinatriuretic pathways such as the renin-angiotensin system, aldosterone and sympathetic nerve activity to the kidneys, and natriuretic pathways such as the natriuretic peptide system (1, 2). Recent evidence has indicated that other natriuretic systems are involved in regulating U Na V, including dopaminergic activity, the kallikrein-kinin system, and other peptide hormonal pathways (2-4). Among these, evidence has been presented that the natriuretic peptide γ-melanocyte-stimulating hormone (γ-MSH) participates in the integrated response to a high intake of dietary sodium: rats ingesting a high-sodium diet (HSD) for 1 week or longer have a marked increase in plasma γ-MSH concentration as well as an increase in the content of γ-MSH in the neurointermediate lobe (NIL) of the The γ-melanocyte-stimulating hormone (γ-MSH) is a natriuretic peptide derived from the N-terminal region of proopiomelanocortin (POMC). Evidence suggests that it may be part of the coordinated response to a low-sodium diet (LSD). We tested the effect of the HSD (8% NaCl) compared with LSD (0.07%) on mean arterial pressure (MAP) in mice with targeted disruption of the PC2 gene (PC2 -/-), necessary for processing of POMC into γ-MSH, or the melanocortin receptor 3 gene (Mc3r -/-; the receptor for MSH). In wild-type mice, HSD for 1 week did not alter MAP versus LSD mice, but plasma γ-MSH immunoreactivity was more than double the LSD value. In contrast, in PC2 -/-mice, MAP on the LSD was not greater than in wild-type mice, but plasma γ-MSH was reduced to one-seventh the wild-type value. On the HSD, MAP rose to a markedly hypertensive level while plasma γ-MSH concentration remained severely depressed. Intravenous infusion of γ-MSH (0.2 pmol/min) for 30 min to PC2 -/-mice after 1 week of HSD lowered MAP from hypertensive levels to normal; infusion of α-MSH at the same rate had no effect. Injection of 60 fmol of γ-MSH into the lateral cerebral ventricle of hypertensive mice also lowered MAP to normal. Administration of a stable analogue of γ-MSH intra-abdominally by microosmotic pump to PC2 -/-mice prevented the development of hypertension when ingesting the HSD. In mice with targeted disruption of the Mc3r gene, the HSD also led to marked hypertension accompanied by elevated plasma levels of γ-MSH; infusion of exogenous γ-MSH to these mice had no effect on MAP. These results strongly suggest that PC2-dependent processing of POMC into γ-MSH is necessary for the normal response to the HSD. γ-MSH deficiency results in marked salt-sensitive hypertension that is rapidly improved with exogenous γ-MSH through a central site of action. α-MSH infused at the same rate had no effect on MAP, indicating that the hypertension is a specific consequence of impaired POMC processing into γ-MSH. Absence of Mc3r produces γ-MSH resistance and hypertension on the H...

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic disruption of γ-melanocyte–stimulating hormone signaling leads to salt-sensitive hypertension in the mouse

Ni¹,

Pearce²,

Butler³

et al. 2003

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Nevertheless, cells with histochemical and immunocytochemical features of melanotrophs can be identified in the human pituitary, 3,[33][34][35] and immunoreactive ␥-MSH-like material has been identified in human plasma. 36,37 In addition, components of this system are found in a variety of extrapituitary tissues. 12 The possibility that the peptide could cause some forms of idiopathic hyperaldosteronism was raised several years ago.…”

Section: Discussionmentioning

confidence: 99%

Suppression of γ-Melanocyte–Stimulating Hormone Secretion Is Accompanied by Salt-Sensitive Hypertension in the Rat

Mayan

Ni²,

Almog³

et al. 2003

Hypertension

View full text Add to dashboard Cite

Abstract-␥-Melanocyte-stimulating hormone (␥-MSH) is a natriuretic peptide derived from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL); its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl) compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated through dopaminergic pathways, we asked whether dopaminergic stimulation with bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5 mg/kg IP for 1 week) alters the ␥-MSH response to a HSD. In vehicle-treated rats, plasma ␥-MSH and NIL ␥-MSH content on the HSD were both markedly elevated over values in rats on the LSD (PϽ0.001); no difference in mean arterial pressure (MAP) occurred. In haloperidol-treated rats on the LSD, both plasma ␥-MSH and NIL ␥-MSH content were greater than in vehicle-treated rats (PϽ0.05) and did not increase further on the HSD; MAP was also no different. In bromocriptine-treated rats, neither plasma ␥-MSH nor NIL ␥-MSH content increased on the HSD versus LSD, and MAP was markedly elevated on the HSD ( Key Words: natriuretic peptides Ⅲ pituitary Ⅲ hypertension, sodium-dependent Ⅲ dopamine M elanocyte-stimulating hormones (MSHs) are peptides of ␣, ␤, and ␥ primary structure, which are derived from the ACTH/␤-endorphin precursor proopiomelanocortin (POMC). Identified initially from the property of ␣-and ␤-MSH to induce melanin dispersion in melanocytes of fish and amphibians, they are highly conserved in mammalian species, where their pigmentary function is minor. This has suggested that they may serve other important biological functions, and roles in inflammation, temperature regulation, satiety, and cardiovascular control have all been indicated. [1][2][3][4] Each of the MSH peptides is also natriuretic, 5-8 and the plasma concentration and pituitary content of ␥-MSH immunoreactivity increase in rats fed a high sodium diet (HSD). 9,10 Additional support for a role in sodium homeostasis comes from the observations that an HSD increases the mRNA abundance of POMC and of the prohormone convertase enzymes PC1 and PC2 involved in its processing into ␥-MSH in the neurointermediate (NIL) of rat pituitary but not the anterior lobe (AL). 9,10 We have recently observed that genetic deficiency of circulating ␥-MSH caused by disruption of the PC2 gene is accompanied by marked salt-sensitive hypertension, 11 further suggesting an important role of this peptide in sodium metabolism and blood pressure control.POMC synthesis and processing in the NIL are under tonic dopaminergic suppression through the dopamine D 2 receptor 12,13 ; the dopamine agonist bromocriptine suppresses the synthesis of POMC and the processing enzymes PC1 and PC2, whereas the dopamine receptor antagonist haloperidol does the opposite. 14, 15 We asked if dopaminergic manipulation modified in any way the action of a diet high in sodium content to stimulate the abundance of NIL ␥-MSH content and the plasma concentration of ␥-MSH, and, if so, what effect this would have on blood pressure and s...

show abstract

“…Leenders et al (1990) demonstrated that this experimental copious drinking causes a rapid increase in POMC synthesis in melanotrophs, whereas dehydration has the opposite effect. Studies have demonstrated that aldosterone secretion is stimulated by POMC-derived peptides such as α-MSH (Vinson et al, 1984), β-MSH (Yamakado et al, 1980) and γ-MSH (Griffing et al, 1985). These results suggest that the pars intermedia may be involved in regulating plasma aldosterone levels under severe conditions of low plasma sodium conditions, and hydro-mineral metabolism in mammals.…”

Section: Physiological Functions Of Pomc-derived Peptides (Fig 6) (1mentioning

confidence: 98%

The Mammalian Pars Intermedia —Structure and Function—

Takeuchi¹

2001

Zoological Science

View full text Add to dashboard Cite

Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension.

Cited by 30 publications

References 60 publications

Genetic disruption of γ-melanocyte–stimulating hormone signaling leads to salt-sensitive hypertension in the mouse

Genetic disruption of γ-melanocyte–stimulating hormone signaling leads to salt-sensitive hypertension in the mouse

Suppression of γ-Melanocyte–Stimulating Hormone Secretion Is Accompanied by Salt-Sensitive Hypertension in the Rat

The Mammalian Pars Intermedia —Structure and Function—

Contact Info

Product

Resources

About