Human Skin: An Independent Peripheral Endocrine Organ

Abstract

The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth factor-binding proteins. Therefore, the human skin fulfils all requirements for being the largest, independent peripheral endocrine organ.

Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes

“…The sebaceous gland is the organ conferring on the skin an independent peripheral endocrine function (6). It also seems to be involved in responses to stress, expressing receptors for ␣-melanocyte-stimulating hormone (␣-MSH; ref.…”

“…Pro-CRH processing into CRH appears to be similar at the central and peripheral levels, including the skin (4). So far, CRH has been detected in epidermal and follicular keratinocytes, melanocytes, endothelial cells, and dermal nerves but not in fibroblasts (4,6). CRH-R1 has been detected in epidermal and follicular keratinocytes, melanocytes, and dermal fibroblasts.…”

“…In analogy with central responses to stress, which involve predominantly the hypothalamic-pituitaryadrenal (HPA) axis, it has been recently proposed that the skin could share similar mediators (3)(4)(5). This postulate was based on the capability of the mammalian skin to produce propiomelanocortin-derived peptides and to be a target of actions through locally expressed melanocortin and opioid receptors (3,6).…”

Age‐specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro

“…Furthermore, as skin is the target for a plethora of hormones and also a peripheral endocrine organ in its own right (Zouboulis, 2000), it can be affected to a large extent by the decline of hormones (Brincat, 2000).…”

Characterization of microfluidic human epidermal keratinocyte culture

“…HEK reside in the basal layer of the epidermis and maintain the skin's homeostatic function in vivo (Zouboulis 2000). Recently, HEK cell cultures have been identified as a possible alternative for animal testing of chemical compounds in dermatotoxicity studies (Bernstein and Vaughan 1999;MonteiroRiviere et al 2003;Roguet 1999;Zucco et al 2004).…”