The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients.
The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 micrograms SMS were injected sc, and plasma GH and insulin and blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P less than 0.001) decreased in seven of eight acromegalic patients from 30 +/- 5 (+/- SE) to an average of 10.7 +/- 4 micrograms/l from 1-10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P less than 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve (P less than 0.01), during the first 3 h after SMS administration. Circulating GH was not altered by SMS or the dopamine agonist mesulergine in one patient, but the combination of both substances (50 micrograms SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 PM, 0.1 nM, and 10 nM SMS or natural somatostatin exerted a similar inhibitory effect (12-39% reduction; P less than 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion, the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore, it may represent a useful tool in the chronic management of this condition.
Lamberts
S W
SW
Oosterom
R
R
Neufeld
M
M
del Pozo
E
E
D000172:Acromegaly / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D015282:Octreotide; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D013006:Growth Hormone; D015282:Octreotide