Gonadotropin-releasing hormone stimulation of pituitary gonadotrope cells produces an increase in intracellular calcium.
Gonadotropin-releasing hormone stimulation of pituitary gonadotrope cells produces an increase in intracellular calcium.
复制标题
促性腺激素释放激素对垂体促性腺细胞的刺激会导致细胞内钙的增加。
DOI：
10.1095/biolreprod32.2.269
复制
发表时间：
1985
影响因子：
3.6
通讯作者：
Conn,PM
中科院分区：
文献类型：
--
作者：
Clapper,DL;Conn,PM
促性腺激素释放激素(GnRH)刺激垂体促性腺激素细胞释放黄体生成素(LH)。先前的研究已经指出了钙离子在这一过程中的作用；然而，本研究首次测量了细胞内钙离子浓度的增加。富含促性腺激素的垂体细胞培养物中加入了Quin2，一种对钙离子敏感的荧光分子。随后加入促性腺激素释放激素后，这些细胞的荧光迅速(在10秒内)增加(表明细胞内游离钙离子增加)。相反，两种GnRH类似物，des1GnRH(GnRH受体的低亲和力结合物)和ac[D-PCL-Phe1，2]DTrp3DLys6DAla10-GnRH(纯GnRH拮抗剂)不产生这种Ca+2变化，从而表明细胞内Ca+2的增加与黄体生成素释放之间存在相关性。通过抑制细胞内高水平Quin-2(以螯合细胞内Ca+2)释放的实验，揭示了细胞内Ca+2释放增加与黄体生成素释放之间的函数关系。由于这种抑制作用可被钙离子载体A23187完全逆转，Quin 2在所用浓度下没有毒性，并通过缓冲细胞内钙离子而明显抑制黄体生成素的释放。这一结果与GnRH刺激的黄体生成素释放是通过细胞内钙离子的增加而介导的假设是一致的，并支持了GnRH刺激的黄体生成素释放的限速步骤位于钙动员的远端的观点。
Gonadotropin-releasing hormone (GnRH) stimulates pituitary gonadotrope cells to release luteinizing hormone (LH). Previous studies have indicated a role for Ca+2in this process; however, the present study provides the first measurements of an increased intracellular Ca+2concentration. Pituitary cell cultures enriched for gonadotropes were loaded with quin 2, a fluorescent Ca+2-sensitive molecule. Subsequent addition of GnRH to these cells produced a rapid (within 10 sec) increase in fluorescence (indicating an increase in intracellular free Ca+2). In contrast, two GnRH analogs, des1GnRH (a very low-affinity binder to the GnRH receptor) and Ac[D-pCl-Phe1,2] DTrp3DLys6DAla10-GnRH (a pure GnRH antagonist) produced no such Ca+2change, thus showing a correlation between increased intracellular Ca+2and LH release. A functional relationship between increased Ca+2and LH release was suggested by experiments in which LH release was inhibited from cells loaded with high levels of intracellular quin 2 (in order to chelate intracellular Ca+2). Since this inhibition was completely reversed by addition of the Ca+2ionophore A23187, quin 2 was not toxic at the concentrations used and apparently inhibited LH release by buffering intracellular Ca+2. The results presented here are consistent with the hypothesis that GnRH-stimulated LH release is mediated by increased intracellular Ca+2and support the notion that the rate-limiting step in GnRH-stimulated LH release is distal to Ca+2mobilization.