Recent advances in the endocrinology of the sebaceous gland.

Dermatoendocrinol. 2017; 9(1): e1361576. Published online 2018 Jan 23. doi: 10.1080/19381980.2017.1361576 PMCID: PMC5821152 PMID: 29484098 Recent advances in the endocrinology of the sebaceous gland Attila G. Szöllősi,a Attila Oláh,a Tamás Bíró,b,* and Balázs István Tótha,* Attila G. Szöllősi aDepartment of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Find articles by Attila G. Szöllősi Attila Oláh aDepartment of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Find articles by Attila Oláh Tamás Bíró bDepartment of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Find articles by Tamás Bíró Balázs István Tóth aDepartment of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Find articles by Balázs István Tóth Author information Article notes Copyright and License information Disclaimer aDepartment of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary bDepartment of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary CONTACT Tamás Bíró, MD, PhD, DSc , Department of Immunology, Faculty of General Medicine, University of Debrecen, H-4032 Debrecen, Egyetem tér 1. *TB and BIT contributed equally to the work. Received 2017 Jun 7; Accepted 2017 Jul 26. Copyright © 2018 The Author(s). Published with license by Taylor & Francis This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. This article has been cited by other articles in PMC. ABSTRACT The sebaceous gland, long considered an evolutionary relic with little-to-no physiological relevance in humans, has emerged in recent decades as a key orchestrator and contributor to many cutaneous functions. In addition to the classical physico-chemical barrier function of the skin against constant environmental challenges, a more novel, neuro-immune modulatory role has also emerged. As part of the complex intercellular communication network of the integumentary system, the sebaceous gland acts as a “relay station” in the skin for many endocrine factors. This review aims to offer a comprehensive overview of endocrine effects and subsequent interactions on this much maligned mini-organ. KEYWORDS: Sebaceous gland, endocrinology, cannabinoid, TRP channels, acne Introduction The sebaceous gland, long considered an evolutionary relic with little-to-no physiological relevance in humans, has emerged as a key orchestrator and contributor to many cutaneous functions. These include the classical physico-chemical barrier function of the skin against constant environmental challenges, as well as more novel, neuro-immune modulatory roles and complex intercellular communication networks of the integumentary system. All of these processes are not only defined by local factors, but greatly influenced by the endocrine system. This review aims to offer a comprehensive overview of endocrine effects and interactions on this much maligned mini-organ. The sebaceous gland – anatomy and functions The sebaceous gland, comprised of sebocytes, is located in the dermis of the skin of all terrestrial mammals, primarily associated with hair follicles and the arrector pili muscles forming the pilosebaceous unit.1,2 There is also great intra-individual variability in the distribution of sebaceous glands, since the density of the glands in various regions of the body is markedly different. The sebaceous gland differentiates in the embryonic stage between months 2 and 4 of gestation, with the rest of the pilosebaceous unit. During this process, a population of B lymphocyte-induced maturation protein 1 expressing unipotent stem cells is established,3 which are responsible for regenerating the sebaceous gland in adult skin, although stem cells from the bulge region of the hair follicle may also act as a source of sebocytes.4,5 The fully formed sebaceous gland found in adult skin may be divided into three zones, containing sebocytes in distinct stages of differentiation. The outermost peripheral zone contains the least differentiated, mitotically active population. These cells grow in size as they move centrally, differentiate, and accumulate lipid droplets, forming the maturation zone. As the final step of their differentiation sebocytes disintegrate and release their content via holocrine section in the central necrosis zone.1,4 This continuous differentiation program is coordinated by a wide range of neural, paracrine, and endocrine mediators,6 the latter of which is the main focus of this review. The main function of the sebaceous gland is the holocrine production of sebum (tallow), the composition of which shows marked species specificity. Sebum is mostly composed of various neutral lipids (triglycerides, free fatty acids, wax esters, cholesterol and squalene), of which squalene and wax esters are unique and typical components. The main function of these secreted lipids is to cover the fur and the surface of the skin, and unsurprisingly they constitute the majority of skin surface lipids.7-9 While sebum plays important roles in the impregnation of fur and thermal insulation as well as the production of pheromones in animals, these functions are mostly unrecognizable in humans, leading to the long-standing view that the human sebaceous gland is an evolutional relic.10,11 This view has changed dramatically over more recent decades, since the composing lipids are important in skin barrier function, water resistance and protection from sunburn and UV radiation,12-14 as well as in the establishment of the commensal bacterial flora of the skin.13,15 The sebaceous gland is not only notable as a producer of sebum, a structural constituent of the skin, but has other functions as well, most notably its contribution to the local immunological milieu. Sebocytes are capable of producing a wide range of (mainly pro-inflammatory) cytokines (interleukin [IL]-1α; IL1-β; IL-6; IL-8/CXCL-8 and tumor necrosis factor-α [TNFα]) and lipid-derived mediators.16,17 The production of these factors is usually initiated by inflammatory factors, such as the presence of bacteria or certain endogenous mediators. Propionibacterium acnes, a known pathogenic factor in the development of acne, leads to the production of TNFα and IL-8/CXCL-8, while bacterial lipopolysaccharide (LPS) elevates IL-1α as well.16 The endogenous inflammatory mediator arachidonic acid (AA) and the elevation intracellular calcium by the ionophore A23187 increased the release of IL-6 and −8.17 Interestingly the activation of the calcium permeable channel, transient receptor potential vanilloid-1 (TRPV (...truncated)