Neuroendocrinology and neurobiology of sebaceous glands

• Published in: Biological reviews of the Cambridge Philosophical Society 2020-06, Vol.95 (3), p.592-624
• Main Authors: Clayton, Richard W., Langan, Ewan A., Ansell, David M., Vos, Ivo J. H. M., Göbel, Klaus, Schneider, Marlon R., Picardo, Mauro, Lim, Xinhong, Steensel, Maurice A. M., Paus, Ralf
• Format: Article
• Language: English
• Subjects: Acne; acne vulgaris; Adrenal glands; Adrenocorticotropic hormone; androgens; Autocrine signalling; Botulinum toxin; Communications systems; Cytokines; Denervation; Epithelial cells; Fibers; Growth hormones; Homeostasis; hormones; Hypothalamus; Hypothyroidism; Inflammation; Lipids; Nerve endings; Nervous system; Neural stem cells; Neuroendocrine system; neuroendocrinology; Neuromodulation; neurons; Neuropeptides; Neurosciences; Neurotransmitters; Paresis; Pathogenesis; Pituitary; Prolactin; Regulators; sebaceous gland; Sebaceous glands; sebum; Skin; Testosterone; Thyroxine; Toxins
• ISSN: 1464-7931; 1469-185X
• DOI: 10.1111/brv.12579

ABSTRACT 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