Nishino K, Hirsch P F, Mahgoub A, Munson P L
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599.
Endocrinology. 1991 May;128(5):2259-65. doi: 10.1210/endo-128-5-2259.
We have confirmed the serum calcium-raising effect of adrenalectomy in young male rats 5-6 h after parathyroidectomy that was first observed by others many years ago. (The phenomenon has also been reported in cats, dogs, and mice.) In addition, we have shown that adrenalectomy raises the serum ionized calcium as well as total calcium and that the effect occurs in young female as well as in young male rats. Furthermore, we have found that the serum calcium-raising effect of adrenalectomy occurs if the adrenalectomy is performed several days before parathyroidectomy or 6 h after parathyroidectomy, as well as at the same time as the parathyroidectomy. When the rats were adrenalectomized 7-9 days before parathyroidectomy and given small daily life-maintaining doses of corticosterone or cortisone acetate, this glucocorticoid treatment did not reverse the adrenalectomy effect. This led us to think at first that the effect of adrenalectomy must be due to the loss of an unknown adrenal factor rather than to loss of glucocorticoid. Additional experiments, however, in which corticosterone or hydrocortisone was administered by continuous release pellets, demonstrated conclusively that a small continuous supply of corticosterone (within the physiological range as determined by immunoassay of plasma) was sufficient to reverse the adrenalectomy effect. The results with hydrocortisone were similar at even lower doses than of corticosterone. Somewhat higher doses of corticosterone or hydrocortisone reduced the serum calcium even below the parathyroidectomy level. In a preliminary investigation of the specificity of the glucocorticoid effect we found that aldosterone, dehydroepiandrosterone, or estradiol had no effect on serum calcium under similar conditions. We conclude that the fall in serum calcium after parathyroidectomy in rats is due in part to the hypocalcemic effect of endogenous corticosterone. Thus, the loss of corticosterone after adrenalectomy explains the serum calcium-raising effect of adrenalectomy in parathyroidectomized rats. These results also suggest that glucocorticoids at physiological levels have a significant effect on calcium metabolism in general.
我们已经证实了多年前他人首次观察到的甲状旁腺切除术后5 - 6小时肾上腺切除术对年轻雄性大鼠血清钙的升高作用。（猫、狗和小鼠中也报道过这种现象。）此外，我们还表明肾上腺切除术会升高血清离子钙以及总钙，并且这种作用在年轻雌性大鼠和年轻雄性大鼠中均会出现。此外，我们发现如果在甲状旁腺切除术数天前、甲状旁腺切除术后6小时或与甲状旁腺切除术同时进行肾上腺切除术，都会出现肾上腺切除术升高血清钙的作用。当在甲状旁腺切除术7 - 9天前对大鼠进行肾上腺切除术，并给予维持日常生活的小剂量皮质酮或醋酸可的松时，这种糖皮质激素治疗并不能逆转肾上腺切除术的效果。这最初使我们认为肾上腺切除术的效果一定是由于某种未知肾上腺因子的丧失，而非糖皮质激素的丧失。然而，随后通过持续释放微丸给予皮质酮或氢化可的松的额外实验确凿地表明，小剂量持续供应皮质酮（在通过血浆免疫测定确定的生理范围内）足以逆转肾上腺切除术的效果。氢化可的松的结果在剂量甚至低于皮质酮时也相似。稍高剂量的皮质酮或氢化可的松会使血清钙降低至甚至低于甲状旁腺切除术后的水平。在对糖皮质激素作用特异性的初步研究中，我们发现在类似条件下醛固酮、脱氢表雄酮或雌二醇对血清钙没有影响。我们得出结论，大鼠甲状旁腺切除术后血清钙的下降部分归因于内源性皮质酮的降钙作用。因此，肾上腺切除术后皮质酮的丧失解释了肾上腺切除术对甲状旁腺切除大鼠血清钙的升高作用。这些结果还表明，生理水平的糖皮质激素总体上对钙代谢有显著影响。
