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Neuroendocrinology and neurobiology of sebaceous glands
Biological Reviews ( IF 10.0 ) Pub Date : 2020-01-22 , DOI: 10.1111/brv.12579
Richard W Clayton 1, 2 , Ewan A Langan 1, 3 , David M Ansell 1, 4 , Ivo J H M de Vos 2 , Klaus Göbel 2, 5 , Marlon R Schneider 6 , Mauro Picardo 7 , Xinhong Lim 8 , Maurice A M van Steensel 2, 8 , Ralf Paus 1, 9, 10
Affiliation  

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.

中文翻译:

皮脂腺的神经内分泌学和神经生物学

神经系统通过神经纤维和下丘脑和垂体神经激素的全身释放与外周组织交流。神经系统与人体最大器官皮肤之间的交流传统上很少受到关注。特别是,很少考虑皮脂腺(SGs)的神经调节,这是一种主要的皮肤附属物。然而,很明显 SG 受到严格的垂体控制,并形成一个迷人的、临床相关的外周靶器官,用于研究上皮的神经内分泌和神经调节。皮脂是 SG 的主要分泌产物,由特殊上皮细胞(皮脂细胞)的全分泌分泌产生的复杂脂质混合物组成。这表明神经内分泌系统在 SG 功能中的作用是,生长激素、甲状腺素或催乳素的过量循环水平导致皮脂产生增加(皮脂溢)。相反,生长激素缺乏、甲状腺功能减退和肾上腺功能不全会导致皮脂分泌减少和皮肤干燥。此外,SGs 的雄激素敏感性似乎受神经内分泌控制,因为垂体切除术(切除垂体)使 SGs 在很大程度上对睾酮的刺激不敏感,这对于维持 SG 稳态至关重要。然而,几种神经激素,如促肾上腺皮质激素和α-黑素细胞刺激素,可以独立于睾丸或肾上腺刺激皮脂产生,进一步强调了神经内分泌控制在 SG 生物学中的重要性。而且,皮脂细胞合成几种神经激素并表达它们的受体,表明存在皮脂细胞调节的神经自分泌机制。除了神经内分泌系统外,可以想象,皮肤神经末梢分泌的神经肽和神经递质也可能作用于皮脂腺细胞或其祖细胞,因为皮肤有丰富的神经支配。然而,迄今为止,SG 发育和功能的神经控制仍然缺乏研究和不完全了解。肉毒杆菌毒素介导或面部麻痹相关的人类皮脂分泌减少表明,皮肤神经源性物质调节皮脂细胞的脂质和炎性细胞因子合成,可能暗示神经系统与痤疮发病机制有关。此外,有证据表明,小鼠皮肤去神经支配改变了 SG 稳态关键调节因子的表达。在这篇综述中,我们检查了有关生理学和病理学中人类 SG 功能的神经内分泌和神经生物学调节的当前证据。我们进一步呼吁关注这一系列研究,作为探索和治疗性操纵神经系统和哺乳动物皮肤之间机械联系的指导模型。
更新日期:2020-01-22
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