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

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.