Aging-Related Changes in Cutaneous Corticotropin-Releasing Hormone System Reflect a Defective Neuroendocrine-Stress Response in Aging

Elewa, Rana; Abdallah, Marwa; Youssef, Nagwa; Zouboulis, Christos C.

doi:10.1089/rej.2011.1294

Cited by 21 publications

(8 citation statements)

References 20 publications

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“…Furthermore, human SGs and SZ95 sebocytes express the receptors for CRH (CRH‐R1 and CRH‐R2), as well as CRH and CRH‐binding protein (CRH‐BP) as indicated in Table (Kono et al ., ; Zouboulis et al ., ; Kim et al ., ; Ganceviciene et al ., ; Elewa et al ., ). Peri‐follicular nerve fibres reportedly also synthesise CRH (Roloff et al ., ; Slominski et al ., ).…”

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

confidence: 97%

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

confidence: 97%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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“…Notably, the SG activity is decreased in aged skin with the reduction of sebum; however, the decline is correlated to sex. 9 Although it has been known that SG differentiation and SG progenitor cells are affected by aging, 10, 11, 12, 13 it remains to be elucidated how aging depletes SG progenitor cells. Interestingly, the mouse with the disruption of stearoyl-CoA desaturase (SCD)1, which is the critical enzyme for fatty acid synthesis, displayed atrophy of SG.…”

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confidence: 99%

p53 induces skin aging by depleting Blimp1+ sebaceous gland cells

Nakasaki

Todorova

et al. 2014

Cell Death Dis

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p53 is an important inducer of organismal aging. However, its roles in the aging of skin remain unclear. Here we show that mice with chronic activation of p53 develop an aging phenotype in the skin associated with a reduction of subcutaneous fat and loss of sebaceous gland (SG). The reduction in the fat layer may result from the decrease of mammalian TOR complex 1 (mTORC1) activity accompanied by elevated expression of energy expenditure genes, and possibly as compensatory effects, leading to the elevation of peroxisome proliferator-activated receptor (PPAR)γ, an inducer of sebocyte differentiation. In addition, Blimp1+ sebocytes become depleted concomitantly with an increase in cellular senescence, which can be reversed by PPARγ antagonist (BADGE) treatment. Therefore, our results indicate that p53-mediated aging of the skin involves not only thinning through the loss of subdermal fat, but also xerosis or drying of the skin through declining sebaceous gland activity.

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“…In our study, the higher levels of checking, slowness, and rumination, found in patients with acne vulgaris, appear to be consistent with the results of the above-mentioned studies, which reported increased frequency of OCD in dermatology clinics. Further support for this suggestion comes from some recent molecular studies showing the involvement of cytokines and corticotropin-releasing hormone in the pathophysiology of acne, factors which are known to play a role in many psychiatric conditions, such as anxiety and depression (30)(31)(32).…”

Section: Discussionmentioning

confidence: 95%

Predictive Value of Obsessive Compulsive Symptoms Involving the Skin on Quality of Life in Patients with Acne Vulgaris

Bez

Yeşilova²,

Arı³

et al. 2013

Acta Derm Venerol

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Acne is one of the most common dermatological diseases, and obsessive compulsive disorder is among the most frequent psychiatric conditions seen in dermatology clinics. Comorbidity of these conditions may therefore be expected. The aim of this study was to measure obsessive compulsive symptoms and quality of life in patients with acne vulgaris, compare them with those of healthy control subjects, and determine whether there is any predictive value of obsessive compulsive symptoms for quality of life in patients with acne. Obsessive compulsive symptoms and quality of life measurements of 146 patients with acne vulgaris and 94 healthy control subjects were made using the Maudsley Obsessive Compulsive Questionnaire and Short Form-36 in a cross-sectional design. Patients with acne vulgaris had lower scores for physical functioning, physical role dysfunction, general health perception, vitality, and emotional role dysfunction. They also had higher scores for checking, slowness, and rumination. The only predictor of physical functioning and vitality dimensions of health-related quality of life in these patients was rumination score. Obsessive compulsive symptoms in patients with acne vulgaris are higher than in controls, and this may correlate with both disease severity and quality of life for patients.

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Aging-Related Changes in Cutaneous Corticotropin-Releasing Hormone System Reflect a Defective Neuroendocrine-Stress Response in Aging

Abstract: Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.

Cited by 21 publications

References 20 publications

Neuroendocrinology and neurobiology of sebaceous glands

Neuroendocrinology and neurobiology of sebaceous glands

p53 induces skin aging by depleting Blimp1+ sebaceous gland cells

Predictive Value of Obsessive Compulsive Symptoms Involving the Skin on Quality of Life in Patients with Acne Vulgaris

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