Hormones and the pilosebaceous unit.

[Dermato-Endocrinology 1:2, 81-86; March/April 2009]; ©2009 Landes Bioscience Special Focus Review Hormones and the pilosebaceous unit Wen-Chieh Chen1 and Christos C. Zouboulis2,3 1Department of Dermatology and Allergy; Technische Universitaet Muenchen; Munich, Germany; 2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany; 3Laboratory of Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology; Institute of Clinical Pharmacology and Toxicology; Charité Universitaetsmedizin Berlin; Berlin, Germany Key words: androgen, dermato-endocrinology, hair follicle, hormone, hormone receptor, sebaceous gland Hormones can exert their actions through endocrine, paracrine, juxtacrine, autocrine and intracrine pathways. The skin, especially the pilosebaceous unit, can be regarded as an endocrine organ meanwhile a target of hormones, because it synthesizes miscellaneous hormones and expresses diverse hormone receptors. Over the past decade, steroid hormones, phospholipid hormones, retinoids and nuclear receptor ligands as well as the so-called stress hormones have been demonstrated to play pivotal roles in controlling the development of pilosebaceous units, lipogenesis of sebaceous glands and hair cycling. Among them, androgen is most extensively studied and of highest clinical significance. Androgenmediated dermatoses such as acne, androgenetic alopecia and seborrhea are among the most common skin disorders, with most patients exhibiting normal circulating androgen levels. The “cutaneous hyperandrogenism” is caused by in stiu overexpression of the androgenic enzymes and hyperresponsiveness of androgen receptors. Regulation of cutaneous steroidogenesis is analogous to that in gonads and adrenals. More work is needed to explain the regional difference within and between the androgn-mediated dermatoses. The pilosebaceous unit can act as an ideal model for studies in dermato-endocrinology. Hormones are substances produced and released by cells to affect the other cells. The hormone action can be further divided into five categories according to the location of the target cells; (1) endocrine: the target cells are remote to the producing cells and will be reached via circulating blood, (2) paracrine: the target cells are in the neighborhood of the producing cells, (3) juxtacrine: the target cells are directly adjacent to the producing cells with connections in linkage,1 (4) autocrine: the target cells are the producing cells per se, from which the hormones will be released and turn back, (5) intracrine: the target cells are also the producing cells but the synthesized hormones exert their action without release into the intercellular compartment.2 *Correspondence to: Wen-Chieh Chen; Department of Dermatology and Allergy, Technische Universitaet Muenchen, Biedersteinerstrasse 29, 80802 Munich; Germany; Email: / Christos C. Zouboulis; Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Auenweg 38; Dessau 06847 Germany; Tel.: +49.340.5014000; Fax: +49.340.5014025; Email: Submitted: 01/15/09; Accepted: 03/09/09 Previously published online as a Dermato-Endocrinology E-publication: http://www.landesbioscience.com/journals/dermatoendocrinology/article/8354 www.landesbioscience.com Hormones can be classified based on their chemical structures: (1) amino acid derivatives from tyrosine (e.g., thyroxine, epinephrine/ norepinephrine, dopamine), from tryptophan (e.g., serotonin, melatonin), or from histidine (histamine); (2) oligopeptide hormones (e.g., oxytocin, vasopressin), polypeptide or protein hormones (e.g., α-melanocyte stimulating hormone, corticotropin releasing hormone, adrenocorticotropic hormone) glycoprotein hormones (e.g., luteinizing hormone, human chorionic gonadotropin); (3) fatty acid derivatives such as steroid hormones (e.g., testosterone (T), estradiol) and phospholipids (prostaglandin E2 and prostaglandin F2α). Hormones can be termed according to their origin; thyroid hormones are conventionally produced by thyroid glands, prostaglandins are first isolated from seminal fluid, and most neuromediators are initially identified in the nervous system. Hormones can be grouped together according to the target organs they work on, e.g., androgens and estrogens are sex hormones because they influence primarily the development and function of sexual organs. Hormones with identical molecular formation of the corresponding receptors are known to have close interaction in their functions, such as the steroid nuclear receptor superfamily encompassing steroid hormone receptors, thyroid hormone receptors, retinoid receptor, vitamin D receptor and peroxisome proliferator-activated receptors. However, these conventional concepts of hormone classifications have been complicated by the identification of diverse sources of hormones, multiplicity of hormone actions and extensive distribution of hormone receptors. For example, human skin has been demonstrated to be able to produce many steroid hormones and neuromediators, and meanwhile to express the corresponding receptors.3-5 There is substantial experimental evidence indicating the influence of sex hormones on immunity and allergy development,6 and the effect of neuromediators on the physiology and pathology of pilosebaceous units.4,5 The hormone research in dermatology, coined as “DermatoEndocrinology”, is characterized by the following hallmarks: (1) skin is an endocrine organ per se and can synthesize diverse hormones; (2) skin is also the target of hormones and expresses many more hormone receptors as have been identified; (3) the hormones generated in or by the skin can exert systemic effects; (4) the “intracrine action” is very important for hormone effects on the skin, especially regarding sex hormones.7 Within the skin, the pilosebaceous unit is the main factory for hormone production.3 Moreover, the complexity of hair cyle and the active lipogenesis of sebaceous glands have stimulated the study on the expression of miscellaneous hormone receptors in the Dermato-Endocrinology 81 Hormones and the pilosebaceous unit pilosebaceous unit. Table 1 summarizes the current understanding of the expression of various hormones and their receptors in the pilosebaceous unit based on the chemical structure of hormones.8-73 There is overlapping as well as discrepancy between sebaceous glands and hair follicles. Most well studied are steroid hormones, their releasing hormones and retinoids. Rapidly increasing knowledge has been obtained from the studies on neuromediators and phospholipids (eicosanoids). Of high potential is the research on the role of adipose tissue hormones or adipokines in sebocyte biology.74 Not much is known about the expression of exocrine hormones in the pilosebaceous unit. Androgens are among the most well studied hormones in cutaneous biology. The classical androgen-dependent dermatoses, acne, androgenetic alopecia (AGA) (...truncated)