Naor Z, Snyder G, Fawcett C P, McCann S M
J Cyclic Nucleotide Res. 1978 Dec;4(6):475-86.
In continuing studies on cyclic nucleotide involvement in the regulation of gonadotropin release, we have measured the cyclic nucleotide content and rate of LH and FSH release during stimulation by LHRH of dispersed overnight cultured cells from the pituitaries of adult female rats. The minimal effective concentration of LHRH was 0.1 nM and half maximal stimulation of gonadotropin release was observed in the presence of 1.0 nM LHRH. Significant release of both LH and FSH was detectable after only 10 min in the presence of 5 nM LHRH. The presence of fetal calf serum (FCS) in the overnight culture medium increased basal cGMP levels significantly, whereas horse serum (HS) had no effect, therefore all experiments were conducted on cells cultured in the presence of HS. Treatment of the cultured cells with the phosphodiesterase inhibitors theophylline (TH) or isobutyl-methyl-xanthine (MIX) revealed a preferential stimulatory effect of TH on basal cAMP levels and of MIX on cGMP levels. Throughout these experiments, LHRH had no effect on cAMP levels. In the presence of MIX, concentrations of the releasing hormone as low as 1 nM induced a significant rise in the level of cGMP whereas in its absence, cGMP levels appeared to be unchanged by LHRH. The increase was detectable after 10 min of incubation. MIX alone slightly increased LH and FSH release and significantly potentiated the response of the cells to increasing doses of LHRH up to, but not beyond, 10 nM. The data support the possibility that cGMP may be involved in the mechanism of action of LHRH.
在关于环核苷酸参与促性腺激素释放调节的持续研究中，我们测定了成年雌性大鼠垂体分散过夜培养细胞在促性腺激素释放激素（LHRH）刺激下的环核苷酸含量以及促黄体生成素（LH）和促卵泡生成素（FSH）的释放速率。LHRH的最小有效浓度为0.1 nM，在1.0 nM LHRH存在时观察到促性腺激素释放的半最大刺激。在5 nM LHRH存在下仅10分钟后，即可检测到LH和FSH的显著释放。过夜培养基中胎牛血清（FCS）的存在显著提高了基础环鸟苷酸（cGMP）水平，而马血清（HS）则无影响，因此所有实验均在含有HS的培养基中培养的细胞上进行。用磷酸二酯酶抑制剂茶碱（TH）或异丁基甲基黄嘌呤（MIX）处理培养细胞，结果显示TH对基础环磷酸腺苷（cAMP）水平有优先刺激作用，而MIX对cGMP水平有刺激作用。在整个这些实验中，LHRH对cAMP水平无影响。在MIX存在的情况下，低至1 nM的释放激素浓度即可诱导cGMP水平显著升高，而在其不存在时，LHRH似乎对cGMP水平无影响。孵育10分钟后即可检测到这种升高。单独使用MIX可轻微增加LH和FSH的释放，并显著增强细胞对高达但不超过10 nM的递增剂量LHRH的反应。这些数据支持cGMP可能参与LHRH作用机制的可能性。
