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Effects of Chronic Octreotide Treatment on GH Secretory Dynamics and Tumor Growth in Rats Bearing an Ectopic Somatotroph (GC) Tumor
Author(s) -
Mounier Françoise,
BluetPajot Marie Thérèse,
Viollet Cécile,
Bertherat Jérôme,
Timsit José,
Tannenbaum Gloria S.,
Epelbaum Jacques
Publication year - 1995
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1995.tb00803.x
Subject(s) - endocrinology , medicine , somatostatin , octreotide , somatostatin receptor , in vivo , acromegaly , biology , pituitary tumors , somatostatin receptor 2 , hormone , growth hormone , microbiology and biotechnology
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 μg/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.