An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3

• Published in: Cell 1999-02, Vol.96 (4), p.507-515
• Main Authors: Nykjaer, A, Dragun, D, Walther, D, Vorum, H, Jacobsen, C, Herz, J, Melsen, F, Christensen, E I, Willnow, T E
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0092-8674
• DOI: 10.1016/s0092-8674(00)80655-8

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.