BACKGROUND: According to the existence in anorexia nervosa (AN) of peripheral growth hormone (GH) resistance, low circulating insulinlike growth factor I (IGF-I) levels may be coupled with GH hypersecretion; however, there is also evidence for alterations in the neural control of GH secretion. In fact, reportedly GH secretion is partially refractory to the inhibitory effect of muscarinic cholinergic antagonists as well as to the stimulatory effect of muscarinic cholinergic agonists, which act via opposite modulation of hypothalamic somatostatin (SS) release. Thus, somatostatinergic activity could be impaired in AN. This could be due to an impaired hypothalamic SS release or, alternatively, an altered somatotroph sensitivity to SS. METHODS: We studied in 10 women with AN in acute phase (AN, age, mean +/- SEM: 18.7 +/- 0.8 years) the effect of exogenous SS1-14 (25 and 75 micrograms/hour i.v., infused from +15 to +75 min), at doses that had previously been shown capable of increasing circulating SS levels within the physiological range, on the GH response to GH-releasing hormone (GHRH) (1 microgram/kg i.v. at 0 min). The same study protocol was performed in 8 normal age-matched women (NW, 22.9 +/- 1.0 years). RESULTS: In AN patients, IGF-I levels were lower (p < .01) than those in NW, while basal GH levels were similar in both groups. The GHRH-induced GH rise in AN was higher (p < .01) than that in NW. In AN, the exaggerated GH response to GHRH was inhibited to the same extent by both SS doses (p < .05) and became similar to that after GHRH alone in NW. In NW both 25 and 75 micrograms/hour SS decreased the GHRH-induced GH response; however, the inhibitory effect of the lower dose did not attain statistical significance, whereas the higher dose did (p < .02). During SS infusion, the GHRH-induced GH response in NW was persistently lower (p < .02) than that in AN. The percent inhibitory effect of SS on the somatotroph responsiveness to GHRH was similar in both groups at each dose. CONCLUSIONS: Our present findings demonstrate that the sensitivity of somatotroph cells to exogenous SS given at physiological doses is preserved in patients with AN. It is noteworthy that, during the infusion of physiological SS doses, the GH response to GHRH in AN overlaps on that to GHRH alone under physiological conditions. Thus, in AN, the sensitivity of somatotroph cells to SS apparently being preserved, an impairment of somatostatinergic neurons cannot be ruled out.
Effect of somatostatin infusion on the somatotrope responsiveness to growth hormone-releasing hormone in patients with anorexia nervosa.
FERDEGHINI, Marco;
1999-01-01
Abstract
BACKGROUND: According to the existence in anorexia nervosa (AN) of peripheral growth hormone (GH) resistance, low circulating insulinlike growth factor I (IGF-I) levels may be coupled with GH hypersecretion; however, there is also evidence for alterations in the neural control of GH secretion. In fact, reportedly GH secretion is partially refractory to the inhibitory effect of muscarinic cholinergic antagonists as well as to the stimulatory effect of muscarinic cholinergic agonists, which act via opposite modulation of hypothalamic somatostatin (SS) release. Thus, somatostatinergic activity could be impaired in AN. This could be due to an impaired hypothalamic SS release or, alternatively, an altered somatotroph sensitivity to SS. METHODS: We studied in 10 women with AN in acute phase (AN, age, mean +/- SEM: 18.7 +/- 0.8 years) the effect of exogenous SS1-14 (25 and 75 micrograms/hour i.v., infused from +15 to +75 min), at doses that had previously been shown capable of increasing circulating SS levels within the physiological range, on the GH response to GH-releasing hormone (GHRH) (1 microgram/kg i.v. at 0 min). The same study protocol was performed in 8 normal age-matched women (NW, 22.9 +/- 1.0 years). RESULTS: In AN patients, IGF-I levels were lower (p < .01) than those in NW, while basal GH levels were similar in both groups. The GHRH-induced GH rise in AN was higher (p < .01) than that in NW. In AN, the exaggerated GH response to GHRH was inhibited to the same extent by both SS doses (p < .05) and became similar to that after GHRH alone in NW. In NW both 25 and 75 micrograms/hour SS decreased the GHRH-induced GH response; however, the inhibitory effect of the lower dose did not attain statistical significance, whereas the higher dose did (p < .02). During SS infusion, the GHRH-induced GH response in NW was persistently lower (p < .02) than that in AN. The percent inhibitory effect of SS on the somatotroph responsiveness to GHRH was similar in both groups at each dose. CONCLUSIONS: Our present findings demonstrate that the sensitivity of somatotroph cells to exogenous SS given at physiological doses is preserved in patients with AN. It is noteworthy that, during the infusion of physiological SS doses, the GH response to GHRH in AN overlaps on that to GHRH alone under physiological conditions. Thus, in AN, the sensitivity of somatotroph cells to SS apparently being preserved, an impairment of somatostatinergic neurons cannot be ruled out.
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