Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs

• Published in: Journal of pediatric surgery 2004-08, Vol.39 (8), p.1220-1225
• Main Authors: Pakarinen, Mikko P., Pirinen, Paula, Lauronen, Jouni, Raivio, Peter, Kuusanmäki, Pekka, Halttunen, Jorma
• Format: Article
• Language: English
• Subjects: Absorption; Animals; Autonomic Denervation; autotransplantation; bile acids; Bile Acids and Salts - metabolism; cholesterol; Cholesterol - analogs & derivatives; Cholesterol - biosynthesis; Cholesterol - pharmacokinetics; Cholesterol, Dietary - pharmacokinetics; denervation; Drug Evaluation, Preclinical; Feces - chemistry; Female; growth hormone; Human Growth Hormone - pharmacology; Human Growth Hormone - therapeutic use; Ileum - transplantation; Intestinal Absorption - drug effects; Intestinal Mucosa - enzymology; Intestinal Mucosa - ultrastructure; jejunoileum; Jejunum - transplantation; Laparotomy; Lipids - blood; Malabsorption Syndromes - blood; Malabsorption Syndromes - drug therapy; Malabsorption Syndromes - etiology; Phytosterols - pharmacokinetics; pig; Postoperative Complications - blood; Postoperative Complications - drug therapy; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Sitosterols - pharmacokinetics; Sus scrofa; synthesis; Transplantation, Autologous
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2004.04.017

Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum. Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups. These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.