ABSTRACT

Vitamin D may regulate pituitary function, as there are selective effects of 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) on gene expression in clonal pituitary tumour cells, and on TRH-induced TSH release in normal rat pituitary cells in vitro. The role of Ca²⁺ in 1,25-(OH)₂D₃-enhanced TSH release from primary rat pituitary cell cultures was investigated. Pretreatment with 10 nmol 1,25-(OH)₂D₃/l for 24 h augmented KCl (3–60 mmol/l)-induced TSH release over 1 h at all KCl concentrations greater than 7·5 mmol/l (P< 0·001), with a 76% enhancement of TSH release induced by 30 mmol KCl/l (P<0·001). The Ca²⁺ channel antagonist nifedipine (10 nmol/l–10 μmol/l) caused a concentration-dependent inhibition of KCl (60 mmol/l)-induced TSH secretion. Pretreatment with 1,25-(OH)₂D₃ enhanced KCl-induced release at all concentrations of nifedipine (P<0·001). The Ca²⁺ selective divalent cation ionophore ionomycin (1 nmol/l–1 μmol/l), and the Ca²⁺ channel agonist BAY K 8644 (10 nmol/l–1 μmol/l) increased prolactin secretion but did not increase TSH release, and 1,25-(OH)₂D₃ had no effect. At an extracellular Ca²⁺ concentration of less than 500 nmol/l, TRH-induced TSH release was observed only after treatment with 1,25-(OH)₂D₃ (P<0·01). As the extracellular Ca²⁺ concentration was increased, greater increments of TRH-induced TSH release were observed following pretreatment with 1,25-(OH)₂D₃ (P<0·01). However, the effect of 1,25-(OH)₂D₃ in the thyrotroph was independent of the pretreatment extracellular Ca²⁺ concentration. We have shown that 1,25-(OH)₂D₃ acts selectively on the thyrotroph to enhance in-vitro responsiveness to TRH and KCl. These data suggest that the action of 1,25-(OH)₂D₃ in the thyrotroph is to enhance intracellular signal transduction. They further support a permissive or regulatory role of vitamin D in the normal pituitary gland.

Journal of Endocrinology (1989) 121, 441–450

ABSTRACT

The hormone 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) has been shown to selectively enhance agonist-induced TSH release in the rat thyrotroph in vitro. The interaction of 1,25-(OH)₂D₃ with tri-iodothyronine (T₃) and cortisol was studied in primary cultures of dispersed anterior pituitary cells. TRH (1 nmol/l)-induced TSH release over 1 h was enhanced by 70% (P<0·01) following exposure to 10 nmol 1,25-(OH)₂D₃/l for 24 h. Pretreatment with T₃ (1 pmol/l–1 μmol/l) for 24 h caused a dose-dependent inhibition of TRH-induced TSH release. Net TRH-induced TSH release was inhibited by 85% at T₃ concentrations of 3 nmol/l or greater. Co-incubation with 1,25-(OH)₂D₃ resulted in enhanced TRH-induced TSH release at all T₃ concentrations tested (P<0·001). The increment of TRH-induced TSH release resulting from 1,25-(OH)₂D₃ pretreatment was equivalent in the presence or absence of maximal inhibitory T₃ concentrations. At 1 nmol T₃/1, there was a two- to threefold relative increase in 1,25-(OH)₂D₃-enhanced TRH-induced TSH release. Incubation with cortisol (100 pmol/l–100 nmol/l) had no effect on basal or TRH-induced TSH release, nor did it alter 1,25-(OH)₂D₃-enhanced TRH-induced TSH release when added 24 h before, or at the time of addition of 1,25-(OH)₂D₃. Actinomycin D and α-amanitin abolished 1,25-(OH)₂D₃-enhanced TSH secretion.

These data demonstrate that the action of 1,25-(OH)₂D₃ in the thyrotroph required new RNA transcription, and was not affected by cortisol. In the presence of T₃, the response of the thyrotroph to TRH induced by 1,25-(OH)₂D₃ was increased. We have shown that 1,25-(OH)₂D₃ has significant effects on the action of TRH and T₃ in vitro. These findings support the proposal that 1,25-(OH)₂D₃ may modulate TSH secretion in vivo.

Journal of Endocrinology (1989) 121, 451–458