d'Emden M C, Wark J D
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
J Endocrinol. 1989 Jun;121(3):441-50. doi: 10.1677/joe.0.1210441.
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 less than 0.001), with a 76% enhancement of TSH release induced by 30 mmol KCl/l (P less than 0.001). The Ca2+ channel antagonist nifedipine (10 nmol/l-10 mumol/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 less than 0.001). The Ca2+ selective divalent cation ionophore ionomycin (1 nmol/l-1 mumol/l), and the Ca2+ channel agonist BAY K 8644 (10 nmol/l-1 mumol/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 less than 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 less than 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.
维生素D可能调节垂体功能，因为1,25 - 二羟维生素D3（1,25-(OH)2D3）对克隆垂体肿瘤细胞中的基因表达以及体外正常大鼠垂体细胞中促甲状腺激素释放激素（TRH）诱导的促甲状腺激素（TSH）释放具有选择性作用。研究了钙离子（Ca2+）在1,25-(OH)2D3增强原代大鼠垂体细胞培养物中TSH释放过程中的作用。用10 nmol 1,25-(OH)2D3 /l预处理24小时后，在所有大于7.5 mmol/l的氯化钾（KCl）浓度下，1小时内KCl（3 - 60 mmol/l）诱导的TSH释放均增加（P小于0.001），其中30 mmol KCl/l诱导的TSH释放增强了76%（P小于0.001）。钙离子通道拮抗剂硝苯地平（10 nmol/l - 10 μmol/l）对KCl（60 mmol/l）诱导的TSH分泌产生浓度依赖性抑制作用。用1,25-(OH)2D3预处理后，在所有硝苯地平浓度下KCl诱导的释放均增强（P小于0.001）。钙离子选择性二价阳离子载体离子霉素（1 nmol/l - 1 μmol/l）和钙离子通道激动剂BAY K 8644（10 nmol/l - 1 μmol/l）增加了催乳素分泌，但未增加TSH释放，且1,25-(OH)2D3对此无影响。在细胞外钙离子浓度低于500 nmol/l时，仅在用1,25-(OH)2D3处理后才观察到TRH诱导的TSH释放（P小于0.01）。随着细胞外钙离子浓度增加，用1,25-(OH)2D3预处理后观察到TRH诱导的TSH释放增加幅度更大（P小于0.01）。然而，1,25-(OH)2D3在促甲状腺细胞中的作用与预处理时的细胞外钙离子浓度无关。我们已经表明，1,25-(OH)2D3选择性作用于促甲状腺细胞，以增强体外对TRH和KCl的反应性。这些数据表明，1,25-(OH)2D3在促甲状腺细胞中的作用是增强细胞内信号转导。它们进一步支持了维生素D在正常垂体中的允许或调节作用。
