Influence of Vitamin D₃, 1,25-Dihydroxyvitamin D₃, and 24,25-Dihydroxyvitamin D₃on Parathyroid Hormone Secretion, Adenosine 3 ′,5′-Monophosphate Release, and Ultrastructure of Parathyroid Glands in Organ Culture*

The influence of supraphysiological and physiological concentrations of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] on the endocrine activity of normal porcine parathyroid glands and human parathyroid adenomas in organ culture was studied. In the medium, parathyroid hormone (PTH) and cAMP were measured radioimmunologically and correlated with ultrastructural changes of the tissue. During incubations with 1,25(OH)2D3 (range, 0.03–40.0 ng/ml), PTH secretion decreased uniformly from 100% to an average of 60%. In a dose-response experiment, 0.015 ng/ml 1,25(OH)2D3 was the lowest concentration causing a significant inhibition. After elimination of this steroid, PTH secretion increased to nearly normal values again within 2 h. cAMP release showed parallel changes. Vitamin D3 (4000 ng/ml) and 24,25(OH)2D3 (40.0 and 5.0 ng/58:44ml) had no effect. De novo synthesis of the secreted PTH was checked by incubation with [75Se]methionine; its biological potency was estimated by a two-site coated tube radioassay and a labeled antibody membrane assay. First ultrastructural changes in response to 1,25(OH)2D3 could be observed after 4 h. The cytological signs of suppression further intensified for several days. Vitamin D3 and 24,25(OH)2D3 had no effect on the ultrastructure. Both radioimmunological (PTH and cAMP) and ultrastructural results indicate a complex inhibitory effect of 1,25(OH)2D3 on synthesis and secretion of parathyroid glands in vitro. The results are consistent with the concept of a second feedback regulation for PTH by 1,25(OH)2D3.