Endocrinology and immunology of acne: Two sides of the same coin

Abstract

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

Towards a renaissance of dermatoendocrinology: Selected current frontiers

“…This is further elaborated exemplarily by Briganti et al [52] who examine acne as the phenotypic result of altered dermato‐endocrine responses of human skin, and by Zouboulis, [53] who argues in a provocative and highly stimulating essay that the coordinated activities of endocrinological, metabolic and immunological/inflammatory factors drive acne pathogenesis, with peroxisome proliferator‐activated receptors functioning as a putative regulatory hub, in line with similar arguments that have been developed for the role of these receptors in human hair follicle physiology and pathology [7] . Reader feedback by submission of a Correspondence manuscript to these and all other articles in this Focus Theme Issue is very much welcome, provided that this feedback is combined with the presentation of at least some preliminary, as yet unpublished data (see the applicable authors’ instructions for this novel publication feature in Experimental Dermatology ).…”

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

“…Another common skin disorder ripe for in vitro modelling is acne vulgaris, where genetic predispositions, hormonal changes, stress and environmental factors lead to the formation of microcomedones, [65][66][67] many of which can become inflamed. 68…”

“…Another common skin disorder ripe for in vitro modelling is acne vulgaris , where genetic predispositions, hormonal changes, stress and environmental factors lead to the formation of microcomedones, 65‐67 many of which can become inflamed 68 . Inflammatory microcomedones are caused by hyperseborrhoea, where fatty acid composition of sebum becomes altered, leading to accumulation of peroxidized squalene and favouring expansion of C. acnes 66,69,70 . The condition is aggravated by hair duct clogging with overproduced and abnormally differentiated epidermis.…”

Sebaceous gland: Milestones of 30‐year modelling research dedicated to the “brain of the skin”

“…Interest in SG pathophysiology, frequently with a focus on acne and skin lipids but in meantime also in developmental biology and especially on the role of SG in skin homeostasis, remained unbroken since the publication of our previous review. This is demonstrated, for instance, by recent scholarly reviews on SG physiology, [2] endocrinology and immunology, [3] neurobiology, [4] its roles in acne [4,5] and beyond acne [6] and original works on different areas of SG function, including fascinating research on sebaceous lipogenesis. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Such a development was unthinkable in the 1960s, when the American master of dermatology, Prof. Albert M.…”