Unraveling the Role of Sex Hormones on Keratinocyte Functions in Human Inflammatory Skin Diseases

Abstract

The skin exerts several fundamental functions that are the first physical, chemical and immune barriers to the human body. Keratinocytes, the main cell type of the epidermis, provide mechanical defense, support skin integrity and actively endorse cutaneous immune responses. Not surprisingly, considering these crucial activities, alterations in keratinocyte functions are associated with different inflammatory skin diseases. Recent findings indicate that the skin should not only be regarded as a target for hormones but that it should also be considered as an endocrine peripheral organ that is directly involved in the synthesis and metabolism of these chemical messengers. Sex hormones have multiple effects on the skin, attributed to the binding with intracellular receptors expressed by different skin cell populations, including keratinocytes, that activate downstream signaling routes that modulate specific cellular functions and activities. This review is aimed at reorganizing the current knowledge on the role exerted by sex hormones on keratinocyte function in five different inflammatory skin diseases: Hidradenitis suppurativa; Acne vulgaris; Atopic dermatitis; progesterone hypersensitivity; psoriasis. The results of our work aim to provide a deeper insight into common cellular mechanisms and molecular effectors that might constitute putative targets to address for the development of specific therapeutic interventions.

A case of lichenoid drug eruption associated with relugolix

“…This is supported by the previously reported finding that male atopic dermatitis patients have lower testosterone levels when compared to controls. 7 Similarly, in a clinical study that compared sex hormones in psoriatic and non-psoriatic males, males with psoriasis exhibited lower testosterone levels. 8 …”

Androgens/Androgen Receptor in the Management of Skin Diseases

“…Both the immune response of the skin and the permeability of the skin are influenced by sex hormones, and the balance between the immune response and the regulatory role of the skin barrier may regulate the course of AD. Androgens diminish skin permeability while estrogens strengthen it [57]. Women may be…”

Sex-disaggregated population analysis in patients with hidradenitis suppurativa

“…Accordingly, the results of RNA microarray analyses comparing HS lesions vs. non-lesional skin show an enrichment of molecules regulated by androgen receptors or transcription factors associated with epidermal stem cells ( 32 ). Furthermore, androgen receptor activation might elevate the TNF-α expression by myeloid cells via multiple mechanisms ( 33 ). Both women and men can be affected by HS ( 1 ).…”