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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
Author(s) -
LAMBERTS S. W. J.,
KOETSVELD P.,
HOFLAND L.
Publication year - 1989
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1989.tb01264.x
Subject(s) - medicine , endocrinology , in vivo , acromegaly , in vitro , growth hormone , insulin like growth factor , growth factor , pituitary hormones , hormone , inhibitory postsynaptic potential , biology , receptor , biochemistry , microbiology and biotechnology
SUMMARY 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 50μg 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 < 0.01). There was a close correlation between the in‐vitro inhibitory effects of IGF‐I and SMS 201–995 (P < 0.01). In addition, the acute inhibitory effect of 50 μg SMS 201–995 on circulating GH levels in vivo correlated with the inhibitory effects in vitro of both SMS 201–995 (P < 0.01) and IGF‐I (P < 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. In conclusion: (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.