Hormonal regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and alkaline phosphatase in cultured intestinal mucosa.
The endocrine regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) and of the brush border enzyme alkaline phosphatase (EC 3.1.3.1) was studied in short (2 h) and long term (24 h) organ culture of rabbit ileum mucosa. In contrast to the hepatic enzyme, intestinal reductase is not subject to regulation by insulin or glucagon even at a pharmacological level. This applies to both 'total' and 'active' reductase, prepared in the absence or presence of sodium fluoride, respectively. During culture, there is a gradual, time-dependent increase in the active, dephosphorylated enzyme form. This endogenous activation was found to be unaffected by all hormones tested. Similarly, alkaline phosphatase was not influenced by both pancreatic hormones. In contrast, triamcinolone significantly (P less than 0.05) suppressed reductase in a dose-dependent fashion to 38% of controls after 24 h, but not after 2 h culture. Alkaline phosphatase was induced after both periods, but the effect was more marked after 24 h. A parallel minor stimulation of both enzyme activities was noted in the presence of 10(-9)M triiodothyronine (P less than 0.05), lower and very high (10(-5)M) concentrations were ineffective. In view of the role of glucocorticoids as intestinal growth inhibitors and of thyroid hormones as growth stimulators, it is suggested that changes in reductase reflect alterations of crypt membrane cholesterol synthesis, whereas the induction of alkaline phosphatase is mediated through an enhanced enterocyte regeneration and/or maturation.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007082:Ileum / Q000201:enzymology*; D007328:Insulin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008871:Microvilli / Q000201:enzymology; D009924:Organ Culture Techniques; D011817:Rabbits; D014221:Triamcinolone / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D007328:Insulin; D014284:Triiodothyronine; D014221:Triamcinolone; D005934:Glucagon; D006903:Hydroxymethylglutaryl CoA Reductases; D000469:Alkaline Phosphatase