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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.
Pakarinen
Mikko P
MP
Department of Pediatric Surgery, Children's Hospital, Helsinki, Finland.
Pirinen
Paula
P
Lauronen
Jouni
J
Raivio
Peter
P
Kuusanmäki
Pekka
P
Halttunen
Jorma
J
D000818:Animals; D017763:Autonomic Denervation; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000493:pharmacokinetics*; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000737:chemistry; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D007082:Ileum / Q000637:transplantation*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000648:ultrastructure; D007583:Jejunum / Q000637:transplantation*; D007813:Laparotomy; D008055:Lipids / Q000097:blood; D008286:Malabsorption Syndromes / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010840:Phytosterols / Q000493:pharmacokinetics*; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012855:Sitosterols / Q000493:pharmacokinetics*; D034421:Sus scrofa; D014182:Transplantation, Autologous
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008055:Lipids; D010840:Phytosterols; D011994:Recombinant Proteins; D012855:Sitosterols; D019382:Human Growth Hormone; C021273:campesterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol