The vitamin D endocrine system of human sebocytes

Abstract

Locally produced vitamin D metabolites are of high importance for growth regulation in various tissues. Using real‐time PCR, we have characterized expression of key components of the vitamin D system vitamin D receptor (VDR), vitamin D‐25‐hydroxylase (25OHase), 25‐hydroxyvitamin D−1 α‐hydroxylase (1αOHase), and 1,25‐dihydroxyvitamin D‐24‐hydroxylase (24OHase) in the SZ95 human sebaceous gland cell line. Incubation of SZ95 cells with 1,25‐dihydroxyvitamin D resulted in a dose‐dependent suppression of cell proliferation. RNA levels for VDR, 25OHase, 1αOHase, and 24OHase were characterized in SZ95 cells treated with various vitamin D analogs. In conclusion, our findings demonstrate that key components of the vitamin D system are strongly expressed in the SZ95 human sebaceous gland cell line and that local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation and various other cellular functions in sebaceous glands. Moreover, we conclude that sebaceous glands represent promising targets for therapy with vitamin D analogs or for pharmacological modulation of calcitriol synthesis/metabolism.

Frontiers in sebaceous gland biology and pathology

“…In recent years, it has been shown that epidermal keratinocytes (Fig. 4) and other cell types including Langerhans cells, dermal dendritic cells, macrophages, melanocytes, prostate, lung and colon cancer cells, contain the enzymatic machinery needed to produce 1,25(OH) 2 D 3 (91,92). 1,25(OH) 2 D 3 exerts its effects via binding to a specific nuclear vitamin D receptor (VDR), a ligand‐dependent transcription factor that belongs to the superfamily of steroid/thyroid hormone/retinoid nuclear receptors and that recognizes specific DNA sequences named vitamin D response elements.…”

Vitamin D and the skin: an ancient friend, revisited

“…It has been reported that incubation of the SZ95 human sebaceous gland cell line with 1,25(OH) 2 D 3 results in a dose‐dependent suppression of cell proliferation (7). Using real‐time PCR, it was demonstrated that key components of the vitamin D system (VDR, 25OHase, 1 α OHase, and 24OHase) are strongly expressed in SZ95 cells (7).…”

“…It has been reported that incubation of the SZ95 human sebaceous gland cell line with 1,25(OH) 2 D 3 results in a dose‐dependent suppression of cell proliferation (7). Using real‐time PCR, it was demonstrated that key components of the vitamin D system (VDR, 25OHase, 1 α OHase, and 24OHase) are strongly expressed in SZ95 cells (7). It has been concluded that local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation and various other cellular functions in sebaceous glands and that sebaceous glands represent promising targets for therapy with vitamin D analogues or for pharmacological modulation of calcitriol synthesis/metabolism (7).…”

“…Our knowledge about new important physiological effects of vitamin D metabolites is growing rapidly. Of high importance was the discovery that in contrast to earlier assumptions, skin, prostate, colon, breast and many other tissues express the enzyme to convert 25(OH)D to its active form, 1,25(OH) 2 D (1,4–8,33). The insights into new biological functions of 1,25(OH) 2 D in regulating cell growth, modulating the immune system and the renin–angiotensin system have provided explanations for why reduced sun exposure at higher latitudes is associated with a broad variety of diseases, including an increased risk of dying of many types of cancers, developing type 1 diabetes and multiple sclerosis and having a higher incidence of hypertension (Fig.…”

“…Interestingly, it has been shown that epidermal keratinocytes and various other cell types including macrophages, melanocytes, sebocytes, prostate, cutaneous squamous cell carcinomas, lung and colon cancer cells contain the enzymatic machinery needed to produce 1,25(OH) 2 D 3 (Fig. 1), (4)(5)(6)(7)(8)(9)(10). The vitamin D 3 pathway in human skin is complex and characterized by photochemical activation of 7-dehydrocholesterol (7-DHC), formation of previtamin D 3 , isomerization to vitamin D 3 , enzymatic production of 25OHD 3 , enzymatic generation of 1,25(OH) 2 D 3 , and finally, catabolic degradation of 1,25(OH) 2 D 3 .…”