1,25-DIHYDROXYVITAMIN D3 ENHANCES THYROTROPIN RELEASING HORMONE INDUCED THYROTROPIN SECRETION IN NORMAL PITUITARY CELLS

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Abstract
The findings of specific binding of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in normal rat pituitary tissue and selective effects of 1,25-(OH)2D3 on gene expression in clonal pituitary tumor cells have suggested that vitamin D may regulate pituitary function. Therefore, the in vitro effect of 1,25-(OH)2D3 on normal pituitary cells was investigated. Primary anterior pituitary cell cultures prepared from female rats were maintained in experimental medium .+-. 10-8 M 1,25-(OH)2D3 for up to 24 h and then incubated with fresh experimental medium containing TRH (10-10-10-8 M) or vehicle for 1 h. Pretreatment with 1,25-(OH)2D3 for 24 h led to increased TSH release at all TRH concentrations tested (P < 0.0001), a decrease in the half-maximal stimulatory dose or TRH for TSH release from 2 x 10-9 M to 0.4 x 10-9 M, a 22% increase in maximal TSH release (P < 0.01), and an 81% increase in TSH release at 10-9 M TRH (P < 0.001). 1 x 10-9 M 1,25-(OH)2D3 increased TRH (10-9 M)-induced TSH release by 20% (P < 0.05) but 10-7 M and 10-6 M 25-hydroxyvitamin D3 (25-OH D3) had no effect. The effect of 1,25-(OH)2D3 on TRH (10-9 M)-induced TSH release was evident within 8 h and was maximal by 16 h. There was no effect on basal TSH release, TSH accumulation in the medium in the preceding 24 h nor on cell-associated TSH. 1,25-(OH)2D3 pretreatment had no effect on TRH-induced PRL secretion, PRL accumulation in the medium nor on cell-associated PRL. We have shown that 1,25-(OH)2D3 acts selectively on the thyrotroph to enhance in vitro responsiveness to physiologically relevant concentrations of TRH. These findings are consistent with the reported autoradiographic localization of [3H]-1,25-(OH)2D3 in the thyrotroph and support a permissive or regulatory role of vitamin D in the normal pituitary gland.

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