Decline of hormones with increasing age regulates the biological activity of human sebocytes

Abstract

Hormone deficiency occurring with age leads among other systemic disorders to deterioration of the skin quality. Systemic substitution with estradiol in females and GH in males reversed the observed alterations and retarded the skin aging process in single controlled studies. In order to evaluate the importance of sex steroids and growth factors on skin aging in vitro, human sebocytes were treated with GH, IGF‐I, 17β‐estradiol, DHEA, testosterone and progesterone in combination and as single agents in concentrations corresponding to those circulating in young (f20) and postmenopausal women (f60). Cell proliferation and lipid synthesis were measured by means of the 4‐methylumbelliferyl heptanoate fluorescence assay and nile‐red microassay/fluorescence microscopy, respectively. Cells incubated with all hormones mentioned above at f60 showed significantly lower content of sebaceous lipids (P < 0.001) vs. cells at f20 relating to in vivo observations, which have documented a decline of epidermal lipids in aged skin. While progesterone and DHEA, as single agents, showed no effect on lipid synthesis, after treatment with IGF‐I for 48 h at f20 and f60 concentrations, a significant dose‐dependent increase of neutral (P < 0.001) and polar lipids (P < 0.001) was observed at both concentrations tested. Cell size was also increased. On the other hand, GH at f20 and f60 enhanced significantly the production of neutral (P < 0.01 and P < 0.05, accordingly) and polar lipids (P < 0.05 and P < 0.01, accordingly) in sebocytes but not in such an extent as IGF‐I. 17β‐estradiol induced only polar lipid synthesis (P < 0.01) and cell size. No treatment affected the cell proliferation. In conclusion, sex steroids and growth factors and their decline with age play a key role in the regulation of the lipid synthesis in human sebocytes. Furthermore, among all hormones tested, the GH/IGF‐I axis seems to be the most potent regulator of skin lipids.