Kelijman M, Frohman L A
Department of Internal Medicine, University of Cincinnati, College of Medicine, Ohio 45267.
J Clin Endocrinol Metab. 1990 Jul;71(1):157-63. doi: 10.1210/jcem-71-1-157.
We examined the effect of prior exposure to somatostatin (SRIH) on its inhibition of GH and TSH responses to GHRH and TRH stimulation to determine whether SRIH desensitization has physiological significance in man. Six men received GHRH (1 microgram/kg, iv) and TRH (0.3 microgram/kg, iv) 20 min after starting a saline or SRIH (5.5 ng/kg/min, iv) infusion and again 6 h later. Hormone responses were quantified by measuring the area under the curve, corrected for GH concentration at injection time. Similar results were obtained when GH responses were quantified by measuring the hormone secretory rate using the program Detect. Plasma GH and TSH responses to the two GHRH and TRH injections during saline were similar. However, the effects of prior exposure to SRIH were hormone specific. SRIH blunted GH responses to GHRH at 20 min (1609 +/- 286 micrograms/L.min vs. 451 +/- 224), but did not significantly inhibit the responses 6 h later (1422 +/- 410 micrograms/L.min vs. 1000 +/- 302). In contrast, SRIH inhibition of TSH responses to the two TRH injections was similar (first, 946 +/- 201 micrograms/L.min vs. 700 +/- 148; second, 813 +/- 175 micrograms/L.min vs. 562 +/- 66). We next used these results to study whether the previously reported attenuation of GH responses to repeated GHRH stimulation at 2-h intervals is mediated by SRIH. Eight men received GHRH (1 microgram/kg, iv) 380 min after starting a saline or SRIH (5.5 ng/kg/min, iv) infusion or 90 min after starting a primed (5 mg, iv) infusion of propranolol (80 micrograms/min, iv) and again 2 h later. As in the first protocol, GH responses to GHRH were not inhibited when preceded by a 6-h SRIH infusion. However, the 6-h SRIH infusion resulted in a partial restoration of plasma GH responses to the second GHRH injection (saline infusion: first, 1429 +/- 342 micrograms/L.min; second, 254 +/- 75; SRIH infusion: first, 1042 +/- 247 micrograms/L.min; second, 468 +/- 105). beta-Blockade by propranolol resulted in enhanced GH responses to GHRH, but did not prevent the attenuation of GH responses to the second GHRH injection (first, 1937 +/- 366 micrograms/L.min; second, 614 +/- 99). The desensitization to SRIH inhibition of GH responses to GHRH after a 6-h SRIH infusion provides evidence of physiological consequences of SRIH receptor down-regulation. The impaired GH responses to repeated GHRH stimulation are mediated at least in part by enhanced SRIH secretion, which appears independent of a beta-adrenergic mechanism.
我们研究了预先接触生长抑素（SRIH）对其抑制生长激素（GH）和促甲状腺激素（TSH）对生长激素释放激素（GHRH）和促甲状腺激素释放激素（TRH）刺激反应的影响，以确定SRIH脱敏在人体中是否具有生理意义。六名男性在开始输注生理盐水或SRIH（5.5 ng/kg/min，静脉注射）20分钟后接受GHRH（1微克/千克，静脉注射）和TRH（0.3微克/千克，静脉注射），6小时后再次接受。通过测量曲线下面积来量化激素反应，并根据注射时的GH浓度进行校正。当使用Detect程序通过测量激素分泌率来量化GH反应时，得到了类似的结果。在输注生理盐水期间，两次GHRH和TRH注射引起的血浆GH和TSH反应相似。然而，预先接触SRIH的影响具有激素特异性。SRIH在20分钟时减弱了GH对GHRH的反应（1609±286微克/升·分钟对451±224），但在6小时后并未显著抑制反应（1422±410微克/升·分钟对1000±302）。相比之下，SRIH对两次TRH注射引起的TSH反应的抑制作用相似（第一次，946±201微克/升·分钟对700±148；第二次，813±175微克/升·分钟对562±66）。接下来，我们利用这些结果研究先前报道的每隔2小时重复给予GHRH刺激时GH反应减弱是否由SRIH介导。八名男性在开始输注生理盐水或SRIH（5.5 ng/kg/min，静脉注射）380分钟后或开始给予普萘洛尔（5毫克，静脉注射）预充量（80微克/分钟，静脉注射）90分钟后接受GHRH（1微克/千克，静脉注射），2小时后再次接受。与第一个方案一样，在6小时的SRIH输注之前给予GHRH时，GH反应未被抑制。然而，6小时的SRIH输注导致血浆GH对第二次GHRH注射的反应部分恢复（生理盐水输注：第一次，1429±342微克/升·分钟；第二次，254±75；SRIH输注：第一次，1042±247微克/升·分钟；第二次，468±105）。普萘洛尔的β受体阻滞导致GH对GHRH的反应增强，但并未阻止GH对第二次GHRH注射反应的减弱（第一次，1937±366微克/升·分钟；第二次，614±99）。6小时的SRIH输注后对SRIH抑制GH对GHRH反应的脱敏提供了SRIH受体下调生理后果的证据。对重复GHRH刺激的GH反应受损至少部分是由增强的SRIH分泌介导的，这似乎与β肾上腺素能机制无关。
