AJP - Gastrointestinal and Liver Physiology, Vol 240, Issue 4 274-G280, Copyright © 1981 by American Physiological Society
Hormonal regulation of canine intestinal cholesterol synthesis
M. W. Goodman, W. F. Prigge and R. L. Gebhard
Hormonal regulation of intestinal cholesterol synthesis was studied both in
vitro and in vivo. Cholesterol synthesis rate was determined by measurement
of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) activity
and by incorporation [14C]acetate into sterol. In vitro studies utilized
organ culture of canine ileal mucosa. During 6-h culture, reductase
activity was stimulated sevenfold. Insulin (10-6 M) augmented this rise to
144 +/- 7% of th control activity, while 10(-8) M glucagon, 10(-3) M
adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine
suppressed activity (final reductase activity was 83 +/- 3%, 75 +/- 4%, and
41 +/- 3%, respectively, of cultured control values). In vivo studies
utilized dogs with isolated Thiry-Vella ileal fistulas. In vivo, insulin
doubled reductase activity while glucagon led to a 42 +/- 9% suppression.
It is concluded that insulin and glucagon may be potential physiological
regulators of intestinal cholesterol synthesis. The glucagon effect may be
mediated by cyclic nucleotides.
