New Pharmaceutical Concepts for Sebaceous Gland Diseases: Implementing Today’s Pre-Clinical Data into Tomorrow’s Daily Clinical Practice

Abstract

The human sebaceous gland is a microscopic branched type multiacinar gland been present everywhere on the body except on the palms and soles, whereas they are sparsely located on the dorsum of hands and feet. Several medical conditions are related with sebaceous gland pathology, such as acne, sebaceous hyperplasia, sebaceous adenoma and sebaceous carcinoma. Acne is a common, complex, chronic disorder of the human pilosebaceous unit that mostly occurs in adolescence and young adulthood. The sebaceous gland plays an exquisite role in the initiation of the disease. The multifactorial nature of the pathogenesis of acne includes increased sebum production, alteration of the quality of sebum lipids, inflammatory processes, interaction with neuropeptides and dysregulation of the hormone microenvironment, follicular hyperkeratinization and inflammation maintained by Propionbacterium acnes products within the follicle. On the other hand, the sebaceous gland, as a major and critical compartment of human skin, is also affected through ageing, both intrinsic and extrinsic, which lead to distinct clinical and histological changes. Intrinsic ageing of the sebaceous gland is determined primarily by genetic factors and hormonal status, with androgens playing a major role. A clinical manifestation associated with intrinsic ageing changes is skin xerosis. Extrinsic ageing of human sebaceous gland is mainly caused by accumulating UV irradiation, especially UVA. Photoageing of sebaceous gland is expressed with a wide spectrum of benign and malignant sebaceous tumours, such as sebaceous hyperplasia, sebaceous carcinoma and Muir-Torre syndrome. This review will focus on the pathogenesis of the most common sebaceous gland diseases and their molecular pathways which may represent future pharmaceutical targets.

Differential effectiveness of selected non‐psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment

“…Surprisingly, our results also revealed a very intriguing functional heterogeneity between the pCBs: CBG and CBGV, in contrast to CBC, CBDV and THCV, behaved in an ‘endocannabinoid‐like’ way, and increased sebaceous lipid synthesis of the sebocytes (Fig. a,b) raising the possibility of their administration in the management of conditions, such as dry‐skin syndrome, xerosis and even skin ageing . Thus, although it was not our primary goal, our findings shed some light on the complexity of the signalling pathways activated by the different pCBs: our results on the lipid synthesis (Fig.…”

Endocannabinoid Tone Regulates Human Sebocyte Biology

“…From a clinical point of view, induction of a moderate (not seborrheic or acnegenic) increase in the homeostatic SLP would be highly desirable in the treatment of skin dryness (Kim et al, 2014;Mischo et al, 2014;Shi et al, 2015;Zampeli et al, 2012;Zouboulis and Boschnakow, 2001). Thus, our results suggest that administration of VDM11 (and probably other EMT inhibitors too) may have beneficial effects in such conditions.…”

“…Their clinical significance is also remarkably high, because overproduction and pathologically altered composition of sebum in seborrhea is a key step in the pathogenesis of acne, one of the most prevalent human skin diseases (Kurokawa et al, 2009;Tóth et al, 2011;Zouboulis et al, 2008Zouboulis et al, , 2014. On the other hand, lack of sufficient sebum production in adulthood may contribute to dry skin syndrome, xerosis, or even skin aging and atopic dermatitis (AD) (Kim et al, 2014;Mischo et al, 2014;Shi et al, 2015;Zampeli et al, 2012;Zouboulis and Boschnakow 2001). Moreover, the unique composition of sebum is thought to play an important role in regulating the growth of the cutaneous microbiota by restricting unwanted microbes and promoting preferred ones, thus making homeostatic SG functions important orchestrators of skinmicrobiota crosstalk (Pappas, 2009).…”

Androgens and androgen receptor action in skin and hair follicles

“…One of the best predictors of severe acne are serum levels of DHEA-S and the onset of acne correlates with increased DHEA-S levels during adrenarche [78], 2) Severe acne observed in children suffering Congenital adrenal hyperplasia (CAH) [79] correlates with androgen excess due to the high levels of adrenocorticotrophic hormone (ACTH) induced by low cortisol levels.3) Absence of acne in men with androgen insensitivity or castration before puberty[80], 4) Women with acne treated with antiandrogenic drugs reduced sebum production and improved mild to moderate acne[81,82].The major pathogenic factors involved in acne are infection by Propinobacterium Acnes which promotes perifollicular inflammation, hyperkeratinization that provokes obstruction of the infundibulum, stimulation of sebum production, seborrhea and excessive presence of androgens from local or systemic origin[83][84][85][86]. The activation of innate immunity begins with the interaction of surface proteins from Propinobacterium Acne with Toll Like Receptor-2 (TLR-2) present in sebocytes, keratinocytes and monocytes, inducing proinflammatory cytokines expression[87][88][89][90].…”