Leal-Cerro A, Pumar A, Garcia-Garcia E, Dieguez C, Casanueva F F
Department of Endocrinology, Hospital Virgen del Rocio Sevilla, Spain.
Clin Endocrinol (Oxf). 1994 Nov;41(5):649-54. doi: 10.1111/j.1365-2265.1994.tb01831.x.
In patients with Cushing's syndrome there is a blunted GH response to all types of stimuli. Although inferential data point towards a direct perturbation in the pituitary exerted by glucocorticoids, the basic mechanism is unknown. His-D-TRP-ALA-TRP-D-Phe-Lys-NH2 (GHRP-6) is a synthetic hexapeptide which releases GH by a direct pituitary effect through receptors other than GHRH receptors. Furthermore, the combined administration of GHRH and GHRP-6 is able to induce a large GH discharge even in some pathological states such as obesity, associated with GH blockade. To gain further insight into the disrupted mechanisms of GH secretion, Cushing's syndrome patients were challenged with either GHRH, GHRP-6 or GHRH together with GHRP-6. A group of normal subjects was included for control purposes.
Three different tests were undertaken: (a) GHRH 100 micrograms i.v.; (b) GHRP-6 100 micrograms i.v. and (c) GHRH plus GHRP-6 100 micrograms i.v. of each; administered to each subject on different days, at least 4 days apart.
Ten patients (8 women, 2 men) with untreated Cushing's syndrome, 9 Cushing's disease and 1 adrenal adenoma. Five healthy volunteers (3 women, 2 men) of similar ages served as a control group.
Plasma GH levels were measured by immunoradiometric assay.
The areas under the curve (AUC) of GH secretion (mean +/- SEM in mU/I/120 min) in the control subjects after each test were: GHRH, 1420 +/- 330; GHRP-6, 2278 +/- 290 and GHRH plus GHRP-6, 7332 +/- 592 (P < 0.05 vs each compound alone). The AUCs for Cushing's syndrome patients were: GHRH, 248 +/- 165; GHRP-6 530 +/- 170 and for GHRH plus GHRP-6, 870 +/- 258 (P < 0.05 vs GHRH alone). After the combined stimulus only one out of the ten patients with hypercortisolism showed a GH peak over 20 mU/I, while all the controls had a peak over 84 mU/I.
GHRP-6 induced GH secretion as well as the GH discharge elicited by GHRH and GHRP-6 are considerably reduced in Cushing's syndrome patients. This suggests that the main impairment of GH secretion in that pathological state resides at pituitary level.
库欣综合征患者对所有类型刺激的生长激素（GH）反应均减弱。尽管推断数据表明糖皮质激素对垂体有直接干扰作用，但其基本机制尚不清楚。组氨酸 - D - 色氨酸 - 丙氨酸 - 色氨酸 - D - 苯丙氨酸 - 赖氨酸 - 氨基（GHRP - 6）是一种合成六肽，它通过垂体直接作用，经生长激素释放激素（GHRH）受体以外的受体释放GH。此外，即使在一些如肥胖等与GH分泌受阻相关的病理状态下，联合使用GHRH和GHRP - 6也能够诱导大量GH释放。为了进一步深入了解GH分泌的受损机制，对库欣综合征患者进行了GHRH、GHRP - 6或GHRH与GHRP - 6联合刺激试验。纳入一组正常受试者作为对照。
进行了三项不同的试验：（a）静脉注射100微克GHRH；（b）静脉注射100微克GHRP - 6；（c）静脉注射每种100微克GHRH加GHRP - 6；在不同日期给予每个受试者，间隔至少4天。
10例未治疗的库欣综合征患者（8例女性，2例男性），9例库欣病患者和1例肾上腺腺瘤患者。5名年龄相仿的健康志愿者（3例女性，2例男性）作为对照组。
采用免疫放射分析法测定血浆GH水平。
每次试验后，对照组受试者GH分泌的曲线下面积（AUC，以mU/I/120分钟计，均值±标准误）分别为：GHRH，1420±330；GHRP - 6，2278±290；GHRH加GHRP - 6，7332±592（与单独使用每种化合物相比，P<0.05）。库欣综合征患者的AUC分别为：GHRH，248±165；GHRP - 6，530±170；GHRH加GHRP - 6，870±258（与单独使用GHRH相比，P<0.05）。联合刺激后，10例皮质醇增多症患者中只有1例GH峰值超过20 mU/I，而所有对照组患者的峰值均超过84 mU/I。
库欣综合征患者中，GHRP - 6诱导的GH分泌以及GHRH和GHRP - 6联合引起的GH释放均显著减少。这表明在该病理状态下，GH分泌的主要损害位于垂体水平。
