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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Development / genetics
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Cholestanetriol 26-Monooxygenase
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Endocytosis / physiology*
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Heymann Nephritis Antigenic Complex
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Humans
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Iodine Radioisotopes
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Kidney Tubules, Proximal / chemistry
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Kidney Tubules, Proximal / metabolism*
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Kidney Tubules, Proximal / ultrastructure
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Knockout
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Microscopy, Electron
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Receptors, LDL / genetics
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Receptors, LDL / metabolism
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Steroid Hydroxylases / pharmacokinetics*
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Vitamin D / metabolism*
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Vitamin D Deficiency / genetics
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Vitamin D Deficiency / metabolism
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Vitamin D-Binding Protein / urine
Substances
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Heymann Nephritis Antigenic Complex
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Iodine Radioisotopes
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Membrane Glycoproteins
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Receptors, LDL
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Vitamin D-Binding Protein
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Vitamin D
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Steroid Hydroxylases
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CYP27A1 protein, human
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Cholestanetriol 26-Monooxygenase
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Cyp27a1 protein, mouse