Expression of Melanocortin-5 Receptor in Secretory Epithelia Supports a Functional Role in Exocrine and Endocrine Glands

Kraan, M. van der

doi:10.1210/en.139.5.2348

Cited by 86 publications

(75 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 ± 5 Five melanocortin receptor (MC-R) subtypes have been cloned, and reveal different functions based on localization. 6 MC1-R and MC2-R are the classical melanocytic and adrenocortical receptors in the skin and adrenal cortex respectively. 7,8 MC3-R is principally present in the brain, with low levels of expression in the gut.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II

et al. 2000

View full text Add to dashboard Cite

We review our experience with Melanotan II, a non-selective melanocortin receptor agonist, in human subjects with erectile dysfunction (ED). Melanotan II was administered to 20 men with psychogenic and organic ED using a double-blind placebo-controlled crossover design. Penile rigidity was monitored for 6 h using RigiScan. Level of sexual desire and side effects were reported with a questionnaire.In the absence of sexual stimulation, Melanotan II led to penile erection in 17 of 20 men. Subjects experienced a mean of 41 min Rigiscan tip rigidity b 80%. Increased sexual desire was reported after 13a19 (68%) doses of Melanotan II vs 4a21 (19%) of placebo (P`0.01). Nausea and yawning were frequently reported side effects due to Melanotan II; at a dose of 0.025 mgakg, 12.9% of subjects had severe nausea.We conclude that Melanotan II is a potent initiator of penile erection in men with erectile dysfunction. Our ®ndings warrant further investigation of melanocortin agonists and antagonists on penile erection.

show abstract

Section: Introductionmentioning

confidence: 99%

“…5 MC5-R has been localized in exocrine and endocrine glands including the reproductive tract of the rat. 6,7 Melanocortins in¯uence important homeostatic behaviors mediated by the hypothalamus. Melanocortinergic neurons exert a tonic inhibition of feeding behavior.…”

Section: Introductionmentioning

confidence: 99%

Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The function of MC5R is poorly understood despite its extensive distribution in the periphery (Bednarek et al 2007). MC5R has been identified in exocrine gland tissue and are involved in glandular secretion (van der Kraan et al 1998). Besides the expression in 3T3-L1 cells, MC5R has also been identified in human adipose tissue and associated with obesity phenotypes (Chagnon et al 1997).…”

mentioning

confidence: 99%

Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

Møller

Raun

Jacobsen

et al. 2011

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

The melanocortin receptors (MCRs) belong to the G-protein coupled receptors (family A). So far, 5 different subtypes have been described (MC1R-MC5R) and of these MC2R and MC5R have been proposed to act directly in adipocytes and regulate lipolysis in rodents. Using ACTH and -melanocyte stimulating hormone (-MSH) generated from proopiomelanocortin (POMC), as well as synthetic MSH-analogues to stimulate lipolysis in murine 3T3-L1 adipocytes it is shown that MC2R and MC5R are lipolytic mediators in differentiated 3T3-L1 adipocytes. Involvement of cAMP, phosphorylated extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (PKB), adenosine 5' monophosphateactivated protein kinase (AMPK) and Jun-amino-terminal kinase (JNK) in MCR mediated lipolysis were studied. Interestingly, results obtained in 3T3-L1 cells suggest that lipolysis stimulated by -MSH, NDP--MSH, MT-II, SHU9119and PG-901 is mediated through MC5R in a cAMP independent manner. Finally, we identify essential differences in MCR mediated lipolysis when using 3T3-L1 cells compared to primary adipocytes. INTRODUCTIONThe melanocortin system acts through multiple pathways relevant for the prevention of obesity and obesity-related complications (Cone 1999;Marks et al. 2002;Spiegelman & Flier 2001). The system is acknowledged to have an important function in regulation of satiety and energy expenditure (Yaswen et al. 1999;Spiegelman & Flier 2001;Cheung et al. 1997;Azzara et al. 2002). MC4R knockout mice exhibit a well-described phenotype defined by increased lean body mass and fat mass, hyperphagia and disturbances in the metabolic response to overnutrition (Mountjoy et al. 1994;Huszar et al. 1997;Tschop & Heiman 2001). Furthermore, loss of MC4R function is the most frequent monogenetic alteration in severely obese humans (Krude et al. 1998) and in severe, early onset childhood obesity the frequency of mutations in the MC4R locus is 4-6% (Farooqi et al. 2003). Besides the effect on satiety and energy expenditure, the melanocortin system is believed to influence insulin release and insulin sensitivity (Fan et al. 2000;Huo et al. 2009). The melanocortin peptides and their receptors are also suspected to have a direct lipolytic effect on adipose tissues in rodents (Cho et al. 2005;Boston 1999;Spirovski et al. 1975). However this effect is controversial in humans (Hoch et al. 2007). The effect of melanocortins on adipocytes have by some researchers been explained by neuronal regulation of lipolysis (Brito et al. 2007), since MC4R mRNA has been identified in sympathetic neurons connected to white adipose tissue (WAT), indicating that central MC4R might stimulate lipid mobilization in the periphery (Song et al. 2005). However, studies in differentiated murine 3T3-L1 adipocytes suggest a direct lipolytic effect stimulated by melanocortin peptides ACTH and -MSH (Bradley et al. 2005;Cho et al. 2005), Page 3 of 24 A c c e p t e d M a n u s c r i p t 3 which supports the earlier identification of MC2R and MC5R mRNA in this cell line (Boston & Cone 1996). MC1R...

show abstract

“…O receptor da melanocortina 3 (MC3R) é expresso principalmente no SNC, mas também na placenta, intestino, timo e adipócitos (42). Estudos com camundongos com knock out do gene da POMC (chubby mice) e com camundongos ob/ob sugerem que o MC3R expresso em adipócitos seja importante no aumento do gasto energético e na lipólise mediados pelo α-MSH (43,44).…”

Section: Controle Neuroendócrino Do Pesounclassified

“…O MC5R parece ser importante para a secreção das glândulas exócrinas, para a produção de aldosterona na zona glomerulosa das adrenais e para a modulação imunológica (42).…”

Section: Controle Neuroendócrino Do Pesounclassified

Controle neuroendócrino do peso corporal: implicações na gênese da obesidade

Rodrigues

Suplicy

Radominski

2003

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Arq Bras Endocrinol Metab vol 47 nº 4 Agosto 2003 398 RESUMOO peso corporal é regulado por uma interação complexa entre hormônios e neuropeptídeos, sob o controle principal de núcleos hipotalâmicos. Mutações nos genes de hormônios e neuropeptídeos, de seus receptores ou de elementos regulatórios, têm sido descritas na espécie humana, mas são tidas como raras, não explicando as formas mais comuns de obesidade. No entanto, o estudo destas mutações tem propiciado um grande avanço nos conhecimentos sobre a base genéti-ca e a fisiopatologia da obesidade, possibilitando o estudo e abrindo perspectivas para o desenvolvimento de novas modalidades terapêuti-cas. Recentemente, demonstrou-se que mutações no receptor 4 da melanocortina podiam ser encontradas em até 5% dos casos de obesidade severa, representando até o presente momento a forma mais prevalente de obesidade monogênica na espécie humana. Nesta revisão, são discutidas as diversas mutações descritas nos seres humanos de elementos da rede neuroendócrina de controle do peso corporal, bem como as implicações dos mesmos na gênese da obesidade. A complex hypothalamic network of hormones and neuropeptides regulates body weight. Mutations in these hormones/peptides, their receptors or regulatory elements, have been described in humans, but they are rare and could not explain the commonest forms of obesity. Nevertheless, the study of these mutations has favored a great progress in the knowledge of genetic basis and physiopathology of obesity, opening new perspectives on the therapeutic approach of this prevalent disease. Recently, mutations in the melanocortin 4 receptor have been found in up to 5% of severe obese subjects, being thus far the most prevalent monogenic form of obesity in humans. In this revision, we discuss the mutations described in some elements of the body weight regulation system in humans, and their implications for the genesis of obesity. no aumento global da prevalência da obesidade, há muitas evidências de que a genética contribui substancialmente para a regulação do peso corporal. Estudos de correlação do índice de massa corporal (IMC) em gêmeos monozigóticos, gêmeos dizigóticos, irmãos biológicos e adotivos sugerem que a herança da obesidade é de 50-90% (1). Acredita-se que a revisão Controle Neuroendócrino do Peso Corporal: Implicações na Gênese da Obesidade

show abstract

Expression of Melanocortin-5 Receptor in Secretory Epithelia Supports a Functional Role in Exocrine and Endocrine Glands

Cited by 86 publications

References 0 publications

Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II

Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II

Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

Controle neuroendócrino do peso corporal: implicações na gênese da obesidade

Contact Info

Product

Resources

About