Intrinsic versus Extrinsic Aging: A Histopathological, Morphometric and Immunohistochemical Study of Estrogen Receptor β and Androgen Receptor

Abstract

Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor β (ERβ) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERβ and AR compared to sun-unprotected skin of all age groups. Significantly higher ERβ H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERβ H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERβ and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERβ and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation.

What does androgenetic alopecia have to do with COVID‐19? An insight into a potential new therapy

“…In addition, AR expression is low prior to pubertal maturation and may contribute to the low incidence of severe COVID-19 infection in children. [6][7][8] As such, we propose that the lower rate of severe COVID-19 infection in female patients may be attributed to lower AR expression. 9,10 Additional evidence to the possible implication of androgens in COVID-19 infection severity is found in the molecular mechanism required for SARS-CoV-2 infectivity.…”

Overexpression of Androgen, Oestrogen and Progesterone Receptors in Skin Lesions of Becker’s Naevus

“…A limitation of this study was the small sample size, thus the statistical power may be limited and correlation analysis was not performed between clinicopathological variables and sex hormone receptors. In addition, the sex difference in epidermal AR and ERβ immunoreactivity is insignificant in patients with BN and normal subjects (12,27). The male/female ratio of BN was 4.5:1 in our previous survey (1).…”

“…Oestrogen increases collagen content, dermal thickness and water content in human skin (26). Oestrogen can stimulate keratinocyte proliferation in human epidermis and hair follicles, and suppress epidermal keratinocyte apoptosis (27). Oestrogen was originally described to inhibit lipogenesis in human sebaceous glands, but it had no influence on proliferation of, and lipid synthesis in, SZ95 sebocytes (28).…”

“…Collectively, local balance among androgen, oestrogen and progesterone levels may serve to fine-tune their actions in the target cells (37). Seleit et al (27) found a positive correlation between ERβ and AR immunoreactivity in 60 normal skin samples. However, this study revealed that epidermal AR expression was not correlated with ER and PR expression, except for a direct relationship between ERα and ERβ immunostaining in 20 BN lesions.…”

Role of PGE-2 and Other Inflammatory Mediators in Skin Aging and Their Inhibition by Topical Natural Anti-Inflammatories

“…The clinical signs of intrinsic aging are fine wrinkles, thin and transparent skin, a loss of subcutaneous fat, skin laxity, and dryness [4]. Extrinsic aging encompasses these changes as well as prominent coarse wrinkling, increased and mottled hyperpigmentation, abnormal elastin synthesis (elastosis) [5], significant loss in elasticity, skin roughness, and an increase in both pre-cancerous actinic keratoses lesions and skin cancer [6]. Interestingly, hereditary genetic makeup is thought to account for less than 3% of the visible and measurable changes in skin structure and function that occur as we age [7].…”