UDP-glucuronosyltransferases in human intestinal mucosa

Area of Science:

• Pharmacology
• Biochemistry
• Gastroenterology

Background:

• UDP-glucuronosyltransferases (UGTs) are crucial for drug and xenobiotic metabolism, primarily studied in the liver.
• Extrahepatic expression and function of UGTs, particularly in the human intestine, remain less understood.

Purpose of the Study:

• To characterize UGT2B family isoforms involved in steroid hormone and bile acid glucuronidation in human intestinal microsomes.
• To investigate the expression and activity of specific UGT isoforms (UGT2B4, UGT2B7, UGT1A6) in different segments of the human intestine.

Main Methods:

• Microsomal preparations from human jejunum, ileum, and colon.
• Enzymatic assays for glucuronidation of androsterone, testosterone, hyodeoxycholic acid, lithocholic acid, and small phenols.
• Western blot analysis using specific UGT antibodies.
• RT-PCR for UGT gene expression screening.

Main Results:

• Significant glucuronidation of androsterone and testosterone in the intestine, increasing distally.
• Low glucuronidation activity for hyodeoxycholic acid and no significant activity for lithocholic acid.
• High protein levels for intestinal UGTs recognizing androsterone/testosterone, but UGT2B4 was undetectable.
• RT-PCR confirmed UGT2B7 expression in all intestinal segments, while UGT2B4 and UGT1A6 were absent.

Conclusions:

• The human intestine possesses functional UGT isoforms capable of metabolizing steroid hormones like androsterone and testosterone.
• This study establishes the intestine as a steroid-metabolizing organ, highlighting its role in steroid hormone biotransformation.
• Intestinal UGT expression patterns differ significantly from the liver, with UGT2B7 being a key expressed isoform.