Whitley T H, Stowe N W, Ong S H, ey R L, Steiner A L
J Clin Invest. 1975 Jul;56(1):146-54. doi: 10.1172/JCI108063.
Cyclic AMP and cyclic GMP were measured in rat adrenal glands after either hypophysectomy alone or after hypophysectomy and treatment with ACTH. Adrenal cyclic GMP levels rise in acutely hypophysectomized rats to a maximum at 1 h of approximately 200% of control levels; there is a return to base line at 4-12 h after hypophysectomy. In contrast, adrenal cyclic AMP falls immediately to about 50% of control levels after hypophysectomy and remains at approximately 1 pmol per mg tissue. Doses of ACTH beyond the physiological range markedly suppress adrenal cyclic GMP while producing a 50-fold or greater rise in cyclic AMP in hypophysectomized rats. This pattern of adrenal cyclic GMP rise was unchanged in acutely hypophysectomized animals treated with desamethasone. N-6-2'-0 dibutyryl cyclic AMP acted similarly to the effect of ACTH in bringing about a suppression of adrenal cyclic GMP levels. Physiological i.v. pulse doses of ACTH produced a rapid dose related increase in adrenal cyclic GMP. In vitro incubation of quartered adrenal pairs with 500 mU ACTH produced elevated cyclic AMP levels and suppression of cyclic GMP. Whereas adrenal cyclic AMP fell rapidly to 50% of control levels after hypophysectomy and remained at about 1 pmol per mg tissue for 7 days, adrenal cyclic GMP showed a biphasic rhythm in long-term hypophysectomized animals. After an initial peak at 1 h after hypophysectomy, adrenal cyclic GMP declined to baseline at 4-12 h but thereafter progressively rose with time, eventually reaching levels over 1 pmol per mg tissue. Fluorescent immunocytochemical staining of rat adrenal zona fasciculata showed cyclic AMP largely confined to cytoplasmic elements with little fluorescence contained in nuclei. In constant, cyclic GMP was found discretely positioned in nuclei with prominent fluorescence in nucleoli in addition to cytoplasmic localization. It is concluded that in hypophysectomized rats ACTH, either directly or in conjunction with altertion of adrenal cyclic AMP, appears to be one factor which regulates adrenal cyclic GMP. The direction of cyclic GMP change and the different subcellular localization of the nucleotides suggest divergent roles for cyclic AMP and cyclic GMP in adrenocortical function. Furthermore, our observations suggest a role for adrenal cyclic GMP in nuclear directed events.
在单独垂体切除术后或垂体切除术后并用促肾上腺皮质激素（ACTH）治疗的大鼠肾上腺中，检测了环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）。急性垂体切除术后大鼠肾上腺cGMP水平在1小时时升至最高，约为对照水平的200%；垂体切除术后4 - 12小时恢复至基线水平。相比之下，垂体切除术后肾上腺cAMP立即降至对照水平的约50%，并维持在每毫克组织约1皮摩尔的水平。超出生理范围的ACTH剂量显著抑制肾上腺cGMP，同时使垂体切除术后大鼠的cAMP升高50倍或更多。在用地塞米松治疗的急性垂体切除动物中，肾上腺cGMP的这种升高模式未改变。N - 6 - 2'- O -二丁酰环磷酸腺苷在抑制肾上腺cGMP水平方面的作用与ACTH相似。静脉注射生理脉冲剂量的ACTH会使肾上腺cGMP迅速出现与剂量相关的增加。将肾上腺切成四分之一后与500毫单位ACTH进行体外孵育，会使cAMP水平升高并抑制cGMP。垂体切除术后肾上腺cAMP迅速降至对照水平的50%，并在每毫克组织约1皮摩尔的水平维持7天，而在长期垂体切除的动物中，肾上腺cGMP呈现双相节律。垂体切除术后1小时出现初始峰值后，肾上腺cGMP在4 - 12小时降至基线水平，但此后随时间逐渐升高，最终达到每毫克组织超过1皮摩尔的水平。大鼠肾上腺束状带的荧光免疫细胞化学染色显示，cAMP主要局限于细胞质成分，细胞核内荧光很少。相反，除了细胞质定位外，cGMP在细胞核中呈离散定位，核仁中有明显荧光。结论是，在垂体切除术后的大鼠中，ACTH无论是直接作用还是与肾上腺cAMP的改变共同作用，似乎都是调节肾上腺cGMP的一个因素。cGMP变化的方向以及核苷酸在亚细胞中的不同定位表明cAMP和cGMP在肾上腺皮质功能中具有不同作用。此外，我们的观察结果提示肾上腺cGMP在核定向事件中发挥作用。
