A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids

Eisinger, Magdalena; Li, Wen‐Hwa; Anthonavage, Michael; Pappas, Apostolos; Zhang, Li; Rossetti, Dianne; Huang, Qiuling; Seiberg, Miri

doi:10.1016/j.jdermsci.2011.04.001

Cited by 29 publications

(21 citation statements)

References 51 publications

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“…The function of its MC5R receptor is diverse, ranging from stimulation of sebaceous glands (Eisinger et al, 2011) to immunoregulation (Taherzadeh et al, 1999; Taylor and Namba, 2001), to behavioral effects that include modulation of aggression (Morgan et al, 2004). Because MC5R 's association with schizophrenia was identified against the genetic background of a risk allele for the immunomodulatory kynurenine pathway enzyme TDO2 (Miller et al, 2009), it is most likely that the key action in this case would be the reported inhibition of IFN γ expression by MC5R (Taylor and Namba, 2001).…”

Section: Discussionmentioning

confidence: 99%

Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia

Miller¹

2013

Front. Behav. Neurosci.

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Numerous environmental factors have been identified as influential in the development of schizophrenia. Some are byproducts of modern life, yet others were present in our evolutionary past and persist to a lesser degree in the current era. The present study brings together published epidemiological data for schizophrenia and data on variables related to photic input for places of residence across geographical regions, using rainfall as an inverse, proxy measure for light levels. Data were gathered from the literature for two countries, the former Yugoslavia and Ireland, during a time in the early 20th century when mobility was relatively limited. The data for Yugoslavia showed a strong correlation between hospital census rates for schizophrenia (by place of birth) and annual rain (r = 0.96, p = 0.008). In Ireland, the hospital census rates and first admissions for schizophrenia (by place of permanent residence) showed a trend for correlation with annual rain, reaching significance for 1st admissions when the rainfall data was weighted by the underlying population distribution (r = 0.71, p = 0.047). In addition, across the years 1921–1945, birth-year variations in a spring quarter season-of-birth effect for schizophrenia in Ireland showed a trend for correlation with January-March rainfall (r = 0.80, p ≤ 0.10). The data are discussed in terms of the effect of photoperiod on the gestation and behavior of offspring in animals, and the premise is put forth that vestigial phenotypic plasticity for such photic cues still exists in humans. Moreover, genetic polymorphisms of risk identified for psychotic disorders include genes modulated by photoperiod and sunlight intensity. Such a relationship between phenotypic plasticity in response to a particular environmental regime and subsequent natural selection for fixed changes in the environmentally responsive genes, has been well studied in animals and should not be discounted when considering human disease.

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Section: Discussionmentioning

confidence: 99%

Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia

Miller¹

2013

Front. Behav. Neurosci.

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“…In support of the model of direct action of ACTH and α‐MSH on sebocytes, the melanocortin receptors MC1R (Böhm et al ., ; Zhang et al ., , ; Eisinger et al ., ; Whang et al ., ), MC2R (Hong‐Wei et al ., ) and MC5R (Zhang et al ., , , ; Eisinger et al ., ) are expressed in human SGs (Table ). MC5R is also present in murine SGs (Chen et al ., ; Thiboutot et al ., ).…”

Section: The Hypothalamic–pituitary–adrenal Axis and Melanocortin Systemmentioning

confidence: 99%

“…Importantly, both human and mouse SGs have been shown to express several key ligands and receptors of both the HPA axis and melanocortin system (see Section IV.3; Table ) (Kono et al ., ; Zhang et al ., ; Ganceviciene et al ., ; Eisinger et al ., ), suggesting that not only is the SG competent to respond to the output of these central neuroendocrine axes, but that peripheral equivalents in skin may act as autocrine regulators of SG function.…”

Section: The Hypothalamic–pituitary–adrenal Axis and Melanocortin Systemmentioning

confidence: 99%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

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“…triacylglycerides [TAGs], diacylglycerides [DAGs], and monoacylglycerides [MAGs]), free fatty acids (FFAs), sterols, wax esters (WEs), sterol esters (SEs), and squalene (Drake et al 2008). Sebum contributes to the innate immune system (Georgel et al 2005; Napolitano and Juarez, 1997), pheromone release (Kligman, 1963; Brooke and Decker, 1996; Nassar et al 2008; Muñoz-Romo et al 2012), water repellency (Porter, 2001; Eiseinger et al 2011), hydration and organization of the stratum corneum (Pilgram et al 2001; Smith and Thiboutot, 2008), compound adsorption (Tsai et al 2012), bat communication (Safi and Kerth, 2003), and ultraviolet protection (Picardo, et al 2009; Camera et al 2010) among others (Haffner, 2000). Sebaceous secretions may play a role in the pathogenesis of Psuedogymnoascus destructans , a fungus that causes cutaneous infections in bats (white nose syndrome) and mass mortalities of North American cave species (Blehert et al 2009; Gargas et al 2009; Lorch et al 2011; Minnis and Lindner 2013).…”

Section: Introductionmentioning

confidence: 99%

Glycerophospholipid Analysis of Eastern Red Bat (Lasiurus Borealis) Hair by Electrospray Ionization Tandem Mass Spectrometry

et al. 2014

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Pilosebaceous units found in the mammalian integument are composed of a hair follicle, the proximal portion of the hair shaft, a sebaceous gland, and the erector pili muscle. Pilosebaceous units release protective oils, or sebum, by holocrine secretion onto skin and hair through rupturing of sebocytes. Sebum is largely composed of polar and neutral lipids including glycerolipids, free fatty acids, sterols, wax esters, sterol esters, and squalene. In addition to these lipid classes, there is a small proportion of ionic/anionic glycerophospholipids (GPs). Composition of GPs on hair is rarely addressed despite their broad biological activities as signaling molecules and membrane stability. Furthermore, knowledge on GP composition in bats is lacking. Bat GP composition is important to document due to GP roles ranging from decreasing drag during migration to interaction with the integumentary microbiome. In this study, we analyzed GP molecular composition with liquid chromatography electrospray ionization tandem mass spectrometry and compared GP content to previous literature. A total of 152 GPs were detected. Broad GP classes identified include lysophosphatidylcholine, phosphatidylcholine (PC), lysophosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and phosphatidylglycerol, with PC being the most abundant class. The acyl components were consistent with fatty acid methyl esters and triacylglyceride moieties found in Eastern red bat sebum. GP proportions of the hair surface were different from a previous study on bat lung surfactants. This study determined the broad class and molecular species of bat sebum GPs that may be used in future ecological studies in vespertilionid bats.

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A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids

Cited by 29 publications

References 51 publications

Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia

Evidence for phenotypic plasticity in response to photic cues and the connection with genes of risk in schizophrenia

Neuroendocrinology and neurobiology of sebaceous glands

Glycerophospholipid Analysis of Eastern Red Bat (Lasiurus Borealis) Hair by Electrospray Ionization Tandem Mass Spectrometry

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