Age-dependent influence of octreotide on stimulated pancreatic growth in the postnatal period of rats.
OBJECTIVE
To investigate the effect of long-acting octreotide (SMS 201-995) on the plasma growth hormone level in preweaning rats and to study the growth and composition of the exocrine pancreas in these rats after stimulation by caerulein- and camostate-induced endogenous cholecystokinin (CCK).


METHODS
Wistar rats of both sexes were treated as littermate pairs in two periods of postnatal age, from days 1 to 11 and from days 11 to 21. To stimulate pancreatic growth, caerulein (3 micrograms/kg subcutaneously three times daily) was given from days 1 to 11, and oral camostate (200 mg/kg given once daily) or CCK-8 (10 micrograms/kg subcutaneously three times daily) was administered from days 11 to 21. Octreotide (6 or 15 micrograms/kg subcutaneously twice daily) was administered alone or in combination with caerulein or camostate. The rats were exsanguinated on days 11 or 21, and each pancreas was removed, weighed and analysed.


RESULTS
Caerulein stimulated pancreatic growth and raised the trypsin concentration; camostate induced pancreatic hypertrophy and hyperplasia. By day 11, octreotide had decreased the plasma growth hormone level and the basal pancreatic trypsin concentration and content. Given in combination with caerulein, octreotide reduced the growth hormone level and the stimulated trypsin and DNA contents. By day 21, rats treated with octreotide in the camostate group showed a reduced basal pancreatic trypsin concentration and a decreased basal trypsin content (although the changes were not significant). Plasma growth hormone levels were not significantly reduced.


CONCLUSIONS
The antitrophic pancreatic action of octreotide and its plasma growth hormone-lowering effect were shown in rats during the first 10 days after birth. These effects were less notable from days 11 to 21, a period when CCK receptors increase in number and components of the stimulus-secretion mechanism are mature.
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
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K
Kisfalvi
H
H
Friess
M W
MW
Büchler
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Z
Tulassay
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G
Varga
M
M
Papp
D000704:Analysis of Variance; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D004952:Esters; D005260:Female; D016670:Gabexate / Q000031:analogs & derivatives*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology
D004952:Esters; D005765:Gastrointestinal Agents; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D016670:Gabexate; D002108:Ceruletide; D013006:Growth Hormone; D012844:Sincalide; D015282:Octreotide