Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Involvement of non-classical steroid hormone pathways in photoprotection by vitamin D compounds (#137)

Rebecca S Mason 1
  1. University of Sydney, Sydney, NSW, Australia

The active vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D (1,25D), generally acts by binding to the vitamin D receptor (VDR), which belongs to the nuclear receptor superfamily. The liganded VDR functions as a nuclear transcription factor in conjunction mostly with the retinoid-X receptor, to modulate gene transcription.  There is evidence that in intestinal cells and in osteoblasts, this hormone also activates other signalling pathways, including chloride channel opening.  These early signals appear to be triggered after hormone binding to membrane receptors: the VDR and the endoplasmic reticulum protein 57 (ERp57) also known as protein disulfide-isomerase-A3.  1,25D, derived from vitamin D generated by UVB exposure, also functions in skin to reduce UV-induced DNA damage and skin carcinogenesis. Studies with mutated VDR, siRNA and neutralizing antibodies indicated that 1,25D- mediated reduction of UV-induced DNA damage required both VDR and ERp57, but that a mutated VDR with markedly reduced DNA binding still allowed DNA damage to be reduced by the hormone. In these skin cells, VDR and ERp57 co-immunoprecipitated from non-nuclear cell preparations. In UV-irradiated keratinocytes, 1,25D suppressed phosphorylation of several key signalling proteins, including Akt-Ser473 and ERK-Thr202Y204, in association with functional effects on DNA repair. Other vitamin D and vitamin D-like compounds also contribute to these protective effects in skin, including vitamin D compounds such as 1,25-dihydroxylumisterol, which have no detectable transactivating activity.  The reduction in UV-induced DNA damage by these compounds also depends on both VDR and ERp57.  It seems plausible that a less stringent, non-classical receptor signalling system facilitates photoprotection in skin by a variety of compounds and not just the classic hormone.