Impaired Inhibitory Effects of Somatostatin on Growth Hormone (GH)-Releasing Hormone Stimulation of GH Secretion after Short Term Infusion*

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Abstract
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 wheter SRIH desensitization had physiological significance in man. Six men received GHRH (1 .mu.g/kg, iv) and TRH (0.3 .mu.g/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 hormone specific. SRIH blunted GH responses to GHRH at 20 min (1609 .+-. 286 .mu.g/L.cntdot.min vs. 451 .+-. 224), but did not significantly inhibit the responses 6 h later (1422 .+-. 410 .mu.g/L.cntdot.min vs. 1000 .+-. 302). In contrast, SRIH inhibition of TSH responses to the two (TRH injections was similar (first, 946 .+-. 201 .mu.g/L.cntdot.min vs. 700 .+-. 148; second, 813 .+-. 175 .mu.g/L.cntdot.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 .mu.g/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 propanolol (80 .mu.g/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 .mu.g/L.cntdot.min; second, 254 .+-. 75; SRIH infusion: first, 1042 .+-. 247 .mu.g/L.cntdot.min; second, 468 .+-. 105). .beta.-Blockade by propanolol resulted in enhanced GH responses to the second GHRH, but did not prevent the attenuation of GH responses to the second GHRH injection (first, 1937 .+-. 366 .mu.g/L.cntdot.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 stimulated are mediated at least in part by enhanced SRIH secretion, which appears independent of a .beta.-adrenergic mechanism.

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