Exocrine Gland Dysfunction in MC5-R-Deficient Mice: Evidence for Coordinated Regulation of Exocrine Gland Function by Melanocortin Peptides

Chen, Wenbiao; Kelly, Michele A.; Opitz-Araya, Ximena; Thomas, Ruth E.; Low, Malcolm J.; Cone, Roger D.

doi:10.1016/s0092-8674(00)80467-5

Cited by 449 publications

(378 citation statements)

References 56 publications

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“…28 Disruption of the murine MC5R (melanocortin 5 receptor) gene was shown to result in animals with defective exocrine gland function. 29 GNAL (guanine nucleotide-binding protein) appears to be involved in olfaction. 23 Future efforts will be directed at identifying and investigating candidate genes for HHS in the 18p11.31-p11.23 region.…”

Section: Alopecia In Cases With Chromosomal Abnormalities Affecting 18pmentioning

confidence: 99%

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

et al. 2000

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We report on a three-generation Italian family with dominant transmission of a form of hereditary hypotrichosis simplex (HHS). The nine affected adults presented with sparse, thin and short hair. Somewhat less sparse and longer hair was observed in the two affected young children in the third generation. Reduced hair growth affected the scalp and body, although normal eyelashes, eyebrows and growth of men's beards were observed. No associated abnormality was detected and the overall psychomotor development of the affected individuals was normal. A phenotypic variation was observed amongst the family members and is suggestive of a reduced penetrance of the trait or the effect of a modifying factor. After exclusion, in our family, of linkage to loci previously described in other forms of atrichia or hypotrichosis, we performed a genome-wide linkage analysis, which resulted in a positive lod score at 18p11.32-p11.23. We defined a critical region of about 35 cM flanked by markers D18S853 and D18S40. The highest two-point lod score was obtained with the microsatellite markers D18S1376, D18S53 and D18S453 (lod score of 3.31 at θ = 0.00). The 18p11.32-p11.23 locus represents the first chromosome region shown to be associated with hereditary hypotrichosis simplex.

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Section: Alopecia In Cases With Chromosomal Abnormalities Affecting 18pmentioning

confidence: 99%

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

et al. 2000

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“…The physiological role of MC5R is still a matter of debate, but targeted deletion of the receptor resulted in sebaceous gland deficient secretion (Chen et al, 1997). MC5R function also seems to be related with stress response.…”

Section: Introductionmentioning

confidence: 99%

Melanocortin 5 receptor activates ERK1/2 through a PI3K-regulated signaling mechanism

Rodrigues

Pignatelli

Almeida

et al. 2009

Molecular and Cellular Endocrinology

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receptor activates ERK1/2 through a PI3K-regulated signaling mechanism. Molecular and Cellular Endocrinology, Elsevier, 2009, 303 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t SummaryMelanocortin 5 receptor (MC5R) is a G-protein coupled receptor (GPCR) with high affinity for α-MSH. To unravel some of the downstream cell-signaling pathways activated by this receptor, HEK293 cells were transiently and stably transfected with a vector encoding green fluorescent protein (GFP)-tagged MC5R. In these cells the receptor was correctly addressed to the cell surface and was functional, as shown by the MC5R-induced formation of intracellular cAMP. In fact, the MC5R agonist α-MSH induced a 10 or 16 fold increase (transient or stable cells, respectively) above the cAMP levels found in unstimulated cells. Moreover, in cells stably expressing MC5R-GFP, α-MSH promoted ERK1/2 phosphorylation in a dose-dependent manner (EC50=7.3nM) with the maximal effect occurring after 5min of agonist incubation. The signaling pathway conveyed through ERK1/2 is not linked to cAMP, since the phosphorylation of these kinases is unchanged by the inhibition of adenylyl cyclase. Also, ERK1/2 activation is not significantly affected by PKA, PKC and Akt/PKB specific inhibitors. However, α-MSH-induced ERK1/2 activation is abolished by the PI3K inhibitors wortmannin and LY294002. Altogether, these findings demonstrate that MC5R signals through a PI3K-regulated Akt-independent pathway leading to downstream activation of ERK1/2. The involvement of these MAPK suggests that MC5R could be implicated in cellular proliferation or differentiation mechanisms.

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“…Furthermore, the MC4R has been implicated in feeding behaviors and weight homeostasis [9,11,43]. Targeted deletion of the MC5R gene has implicated that this MCR subtype is involved in the coordination of exocrine gland function [6]. In addition, although not assigned to a single MCR, melanocortins have also been implicated in adipocyte lipolysis, thermal control, immunomodulation, sexual function, and cognition, among other functions [9,43].…”

Section: Introductionmentioning

confidence: 99%

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

et al. 2006

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Exocrine Gland Dysfunction in MC5-R-Deficient Mice: Evidence for Coordinated Regulation of Exocrine Gland Function by Melanocortin Peptides

Cited by 449 publications

References 56 publications

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

An autosomal dominant form of hereditary hypotrichosis simplex maps to 18p11.32–p11.23 in an Italian family

Melanocortin 5 receptor activates ERK1/2 through a PI3K-regulated signaling mechanism

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

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