McFarlane A, Coghlan J, Tresham J, Wintour E M
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Endocrinology. 1995 May;136(5):1821-7. doi: 10.1210/endo.136.5.7720626.
These studies compared the relative potencies of CRF and arginine vasopressin (AVP) as ACTH secretagogues in the sheep. Dose-response curves to CRF (10, 25, 50, and 100 micrograms/h) and AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h) were obtained in five adult sheep, with arterial blood samples taken for CRF, AVP, ACTH, and cortisol measurements to determine the pituitary-adrenal response. It was found that the first dose of CRF increased plasma CRF levels to 444 +/- 79 pg/ml. ACTH levels rose significantly from 28 +/- 5 to 186 +/- 46 pg/ml, with a concurrent rise in cortisol levels from 7 +/- 3 to 44 +/- 9 ng/ml. Although plasma ACTH and cortisol levels remained elevated, higher doses of CRF failed to produce further increases. AVP, at all of the doses studied, did not produce an increase in ACTH levels, although cortisol levels rose significantly by the second dose. In a second series of experiments, animals received a continuous infusion of CRF (10 micrograms/h) alone or in combination with graded doses of AVP (0.3, 1.0, 3.0, and 10.0 micrograms/h for 60 min each). It was found that AVP at the highest dose was able to potentiate the ACTH response to CRF. Lower doses of AVP, which did not stimulate a further increase in ACTH levels were, however, associated with a significant rise in cortisol levels. In conclusion, it was found that although CRF alone was a potent stimulator of ACTH secretion, AVP at the doses studied was not able to elicit an ACTH response in the conscious intact sheep. However, a dose of AVP that was not stimulatory in itself was able to augment the ACTH response to CRF.
这些研究比较了促肾上腺皮质激素释放因子(CRF)和精氨酸加压素(AVP)作为绵羊促肾上腺皮质激素(ACTH)分泌刺激剂的相对效力。在五只成年绵羊中获得了对CRF(10、25、50和100微克/小时)和AVP(0.3、1.0、3.0和10.0微克/小时)的剂量反应曲线,并采集动脉血样以测量CRF、AVP、ACTH和皮质醇,以确定垂体-肾上腺反应。结果发现,第一剂CRF使血浆CRF水平升至444±79皮克/毫升。ACTH水平从28±5皮克/毫升显著升至186±46皮克/毫升,同时皮质醇水平从7±3纳克/毫升升至44±9纳克/毫升。尽管血浆ACTH和皮质醇水平仍保持升高,但更高剂量的CRF未能使其进一步升高。在所研究的所有剂量下,AVP均未使ACTH水平升高,尽管第二剂后皮质醇水平显著升高。在第二系列实验中,动物单独接受持续输注CRF(10微克/小时)或与分级剂量的AVP(0.3、1.0、3.0和10.0微克/小时,各持续60分钟)联合输注。结果发现,最高剂量的AVP能够增强ACTH对CRF的反应。然而,较低剂量的AVP虽未刺激ACTH水平进一步升高,但与皮质醇水平的显著升高有关。总之,研究发现,尽管单独的CRF是ACTH分泌的有效刺激剂,但在所研究的剂量下,AVP在清醒的完整绵羊中未能引发ACTH反应。然而,本身无刺激作用的剂量的AVP能够增强ACTH对CRF的反应。