Cytoplasmic and nuclear binding components for 1alpha25-dihydroxyvitamin D3 in chick parathyroid glands.

Abstract

Specific binding of 1.alpha.,25-dihydroxyvitamin D3 [1.alpha.,25-(OH)2D3] to macromolecular components in the cytoplasm and nucleus is demonstrated in parathyroid glands of vitamin-D-deficient chicks. The interaction of 1.alpha.,25-(OH)2D3 with the cytoplasmic binding component is of high affinity (Kd = 3.2 .times. 10-10 M) and high specificity [1.alpha.,25-(OH)2D3 > 25-hydroxyvitamin D3 > 1.alpha.-hydroxyvitamin D3 > vitamin D3 in competing with radioactive 1.alpha.,25-(OH)2D3]. Both cytoplasmic and nuclear hormone-macromolecular complexes sediment at 3.1 S in 0.3 M KCl-sucrose gradients, and agarose gel filtration of the components indicates an apparent MW of 58,000. The 3.1 S binding molecules are not observed in adrenal gland, testes, liver or kidney, but similar receptors for 1.alpha.,25-(OH)2D3 were found previously in intestine. Macromolecular species with a high affinity and preference for 25-hydroxyvitamin D3 [25-(OH)D3] are also identified in parathyroid cytosol and differ from the parathyroid 1.alpha.,25-(OH)2D3-binding component in that they sediment at 6 S in 0.3 M KCl-sucrose gradients, are observed in all tissues examined, have a higher affinity for 25-(OH)D3 than 1.alpha.,25-(OH)2D3 and are not found in the nucleus of the parathyroid glands, in vitro. The discovery of unique 1.alpha.,25-(OH)2D3-binding components in the parathyroid glands is consistent with the sterol hormone''s action at this endocrine site and possible involvement in the regulation of parathyroid hormone synthesis and secretion.