A close correlation between the inhibitory effects of insulin-like growth factor-I and SMS 201-995 on growth hormone release by acromegalic pituitary tumours in vitro and in vivo.
In the present study we compared the in-vitro effects of IGF-I and SMS 201-995 on GH release by cultured tumour cells obtained from seven acromegalic patients with the preoperative in-vivo GH dynamics, including the acute response to 50 micrograms SMS 201-995 subcutaneously. IGF-I and SMS 201-995 inhibited GH release during a 24 h incubation in four and five of the seven tumour cell preparations, respectively. The inhibitory effect of SMS 201-995 was greater than that exerted by IGF-I (P less than 0.01). There was a close correlation between the in-vitro inhibitory effects of IGF-I and SMS 201-995 (P less than 0.01). In addition, the acute inhibitory effect of 50 micrograms SMS 201-995 on circulating GH levels in vivo correlated with the inhibitory effects in vitro of both SMS 201-995 (P less than 0.01) and IGF-I (P less than 0.05). The inhibitory effects of IGF-I and SMS 201-995 on GH release in vitro were shown to be additive in two of four tumours. There was no relation between the in-vitro effects of IGF-I and/or SMS 201-995 and several in-vivo parameters, including fluctuations in GH levels, sleep-induced GH release, a paradoxical increase of GH in response to TRH, and the circulating IGF-I and PRL levels.


CONCLUSIONS
(1) there is a close correlation between the sensitivity of GH release by cultured human adenoma cells to IGF-I and SMS 201-995. (2) There is also a close correlation between the in-vivo inhibitory effect on GH release of SMS 201-995 and the in-vitro inhibitory effects of both SMS 201-995 and IGF-I. (3) A subgroup of acromegalic patients harbour pituitary tumours in which the qualitative regulation of hormone secretion is similar to that of normal GH secretion.
Lamberts
S W
SW
Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands.
van Koetsveld
P
P
Hofland
L
L
D000172:Acromegaly / Q000209:etiology / Q000503:physiopathology*; D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D004347:Drug Interactions; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide