Effects of chronic octreotide treatment on GH secretory dynamics and tumor growth in rats bearing an ectopic somatotroph (GC) tumor.
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 micrograms/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.
Mounier
F
F
U. 159 INSERM, Paris, France.
Bluet-Pajot
M T
MT
Viollet
C
C
Bertherat
J
J
Timsit
J
J
Tannenbaum
G S
GS
Epelbaum
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology / Q000502:physiology; D006728:Hormones / Q000494:pharmacology*; D006729:Hormones, Ectopic / Q000378:metabolism*; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay; D051381:Rats; D011920:Rats, Inbred WF; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured
D006728:Hormones; D006729:Hormones, Ectopic; D017481:Receptors, Somatostatin; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide