VITAMIN-D INCREASES EXPRESSION OF THE TYROSINE-HYDROXYLASE GENE IN ADRENAL-MEDULLARY CELLS

We examined expression of the 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3 ] receptors in chromaffin cells of the adrenal medulla and the effects of 1,25(OH)(2)D3 on expression of the tyrosine hydroxylase (TH) gene. Accumulation of 1,25(OH)(2)D3 in the nuclei of adrenal medullary cell s, but not in the adrenal cortex, was observed in mice intravenously i njected with radioactively labeled hormone. 1,25(OH)(2)D3 produced con centration-dependent increases in the TH mRNA levels in cultured bovin e adrenal medullary cells (BAMC). The maximal increases (2-3-foId) occ urred at 10(-8) M 1,25(OH)(2)D3. Combined treatment with 1,25(OH)(2)D3 and 20 mu M nicotine had no additive effect on TH mRNA levels suggest ing that transsynaptic (nicotinic) and vitamin D (hormonal) stimulatio n of TH gene expression are mediated through converging mechanisms. In duction of TH mRNA by 1,25(OH)(2)D3 was not affected by calcium antago nist TMB-8. By increasing expression of the rate limiting enzyme in th e catecholamine biosynthetic pathway, 1,25-(OH)(2)D3 may participate i n the regulation of catecholamine production in adrenal chromaffin cel ls. This regulation provides mechanisms through which 1,25(OH)(2)D3 ma y control response and adaptation to stress.