Hormonal regulation of canine intestinal cholesterol synthesis

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.