EFFECTS OF CHRONIC OCTREOTIDE TREATMENT ON GH SECRETORY DYNAMICS AND TUMOR-GROWTH IN RATS BEARING AN ECTOPIC SOMATOTROPH (GC) TUMOR

被引:13
作者
MOUNIER, F
BLUETPAJOT, MT
VIOLLET, C
BERTHERAT, J
TIMSIT, J
TANNENBAUM, GS
EPELBAUM, J
机构
[1] INSERM,U159,F-75014 PARIS,FRANCE
[2] INSERM,U24,F-75015 PARIS,FRANCE
[3] MCGILL UNIV,DEPT PEDIAT,MONTREAL,PQ H3A 2T5,CANADA
[4] MCGILL UNIV,DEPT NEUROL & NEUROSURG,MONTREAL,PQ,CANADA
关键词
SOMATOSTATIN RECEPTOR SUBTYPES; GC PITUITARY CELLS; GH; IGF1; INSULIN;
D O I
10.1111/j.1365-2826.1995.tb00803.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effects of octreotide, a long-acting somatostatin agonist selective of the sstr2/sstr3/sstr5 receptor subtypes, on ectopic GH secretion and tumor growth were investigated in Wistar-Furth female rats implanted with GH secreting (GC) cells which express mostly somatostatin receptors of the sstr1 and sstr2 subtypes. Octreotide dose dependently inhibited thymidine incorporation (-57%) and GH secretion (-41%) from GC cells in culture. In vivo, 6 weeks after GC cell implantation, plasma GH, IGF-1 and insulin levels were highly elevated. Cluster analysis of GH secretory dynamics revealed that GH secretion was less pulsatile in GC-implanted than in control animals. Furthermore, in GC-implanted animals, passive immunization either with SRIH or GHRH antisera did not affect GH plasma levels. Three weeks after GC cell implantation, when tumors became palpable, octreotide (1 mu g/h/kg BW) or saline was infused constantly for three weeks by osmotic minipumps. In octreotide treated rats, GH, IGF-1 and insulin levels were not different from sham-implanted animals and tumors weight were reduced by 80%. High affinity somatostatin binding sites were found in equivalent amounts on tumors from octreotide-treated or saline-treated animals. These findings indicate that GH secretion in GC-rats is mainly derived from the tumors and independent of hypothalamic control and that octreotide reduces both GH secretion and tumor growth. We conclude that the GC-implanted rat represents a good animal model to test the antisecretory and antitrophic properties of somatostatin analogs in vivo.
引用
收藏
页码:645 / 651
页数:7
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