An Endocytic Pathway Essential for Renal Uptake and Activation of the Steroid 25-(OH) Vitamin D3

Cell. 1999 Feb 19;96(4):507-15. doi: 10.1016/s0092-8674(00)80655-8.

Abstract

Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Development / genetics
  • Cholestanetriol 26-Monooxygenase
  • Endocytosis / physiology*
  • Heymann Nephritis Antigenic Complex
  • Humans
  • Iodine Radioisotopes
  • Kidney Tubules, Proximal / chemistry
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / ultrastructure
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Steroid Hydroxylases / pharmacokinetics*
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / metabolism
  • Vitamin D-Binding Protein / urine

Substances

  • Heymann Nephritis Antigenic Complex
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Receptors, LDL
  • Vitamin D-Binding Protein
  • Vitamin D
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Cyp27a1 protein, mouse