It is remarkable that phytoplankton and zooplankton have been producing
vitamin D for more than 500 million years. The role of
vitamin D in lower non-vertebrate life forms is not well understood. However, it is critically important that most vertebrates obtain an adequate source of
vitamin D, either from exposure to sunlight or from their diet, in order to develop and maintain a healthy mineralized skeleton.
Vitamin D deficiency is an unrecognized epidemic in most adults who are not exposed to adequate sunlight. This can precipitate and exacerbate
osteoporosis and cause the painful
bone disease osteomalacia. Once
vitamin D is absorbed from the diet or made in the skin by the action of sunlight, it is metabolized in the liver to
25-hydroxyvitamin D [25(
OH)D] and then in the kidney to
1,25-dihydroxyvitamin D [1,25(
OH)2D]. 1,25(
OH)2D interacts with its
nuclear receptor (VDR) in the intestine and bone in order to maintain
calcium homeostasis. The VDR is also present in a wide variety of other tissues. 1,25(
OH)2D interacts with these receptors to have a multitude of important physiological effects. In addition, it is now recognized that many tissues, including colon, breast and prostate, have the enzymatic machinery to produce 1,25(
OH)2D. The insights into the new biological functions of 1,25(
OH)2D in regulating cell growth, modulating the immune system and modulating the renin-angiotensin system provides an explanation for why diminished sun exposure at higher latitudes is associated with increased risk of dying of many common
cancers, developing
type 1 diabetes and
multiple sclerosis, and having a higher incidence of
hypertension. Another calciotropic
hormone that is also produced in the skin,
parathyroid hormone-related peptide, is also a potent inhibitor of squamous cell proliferation. The use of agonists and antagonists for
PTHrP has important clinical applications for the prevention and treatment of
skin diseases and disorders of hair growth.