Vitamin D endocrine system after short-term space flight

The exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca(2+) metabolism, yet the cellular/molecular mechanisms leading to these changes are poorly understood. There is some evidence for microgravity-induced alterations in the vitamin D endocrine system, which is known to be primarily involved in the regulation of Ca(2+) metabolism. Vitamin D-dependent Ca(2+) binding proteins, or calbindins, are believed to have a significant role in maintaining cellular Ca(2+) homeostasis. We used immunocytochemical, biochemical and molecular approaches to analyze the expression of calbindin-D(sub 28k) and calbindin-D(sub 9k) in kidneys and intestines of rats flown for 9 days aboard the Spacelab 3 mission. The effects of microgravity on calbindins in rats in space vs. 'grounded' animals (synchronous Animal Enclosure Module controls and tail suspension controls) were compared. Exposure to microgravity resulted in a significant decrease in calbindin-D(sub 28k) content in kidneys and calbindin-D(sub 9k) in the intestine of flight and suspended animals, as measured by enzyme-linked immunosorbent assay (ELISA). Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in kidneys and intestine, and insulin in pancreas. There was a large decrease in the distal tubular cell-associated calbindin-D(sub 28k) and absorptive cell-associated calbindin-D(sub 9k) immunoreactivity in the space and suspension kidneys and intestine, as compared with matched ground controls. No consistent differences in pancreatic insulin immunoreactivity between space, suspension and ground controls was observed. There were significant correlations between results by quantitative ICC and ELISA. Western blot analysis showed no consistent changes in the low levels of intestinal and renal vitamin D receptors. These findings suggest that a decreased expression of calbindins after a short-term exposure to microgravity and modelled weightlessness, may affect cellular Ca(2+) homeostasis and contribute to Ca(2+) and bone metabolism disorders induced by space flight.