Impact of androgen and dietary advanced glycation end products on female rat liver

Cell Physiol Biochem. 2015;37(3):1134-46. doi: 10.1159/000430400. Epub 2015 Sep 25.


Background/aims: Advanced glycation end products (AGEs) have been related to a wide range of liver disorders including hyperandrogenic states such as the Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the potential impact of dietary glycotoxins exposure and androgen excess on hepatic histology and biochemistry in an androgenized female rat model.

Methods: The study population consisted of 80 female Wistar rats, divided in 3 groups, a group of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were androgenized via subcutaneous implantation of dihydrotestosterone-containing pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months.

Results: Rats fed with a high-AGE diet exhibited significantly elevated levels of gamma-glutamyl transferase (x03B3;GT) (p≤0.0002) and indices of AGE immunostaining in liver tissue (p<0.01) when compared to the respective low-AGE group, while aspartate aminotransferase (AST) levels were affected only in non-androgenized animals (p=0.0002). Androgenization per se constitutes an aggravating factor as demonstrated by the elevated x03B3;GT levels in adult androgenized animals compared to non-androgenized, independent of diet content (p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by increased immunohistochemical AGE deposition in hepatocytes of the latter categories (p=0.0007).

Conclusion: The present study suggests that androgens and glycotoxins may contribute synergistically to distort hepatic physiology and function as observed in hyperandrogenic conditions.

MeSH terms

  • Androgens / adverse effects*
  • Androgens / pharmacology
  • Animals
  • Dietary Supplements
  • Disease Models, Animal
  • Female
  • Glycation End Products, Advanced / adverse effects*
  • Glycation End Products, Advanced / pharmacology
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Polycystic Ovary Syndrome / chemically induced*
  • Polycystic Ovary Syndrome / enzymology
  • Rats
  • Rats, Wistar
  • gamma-Glutamyltransferase / metabolism*


  • Androgens
  • Glycation End Products, Advanced
  • gamma-Glutamyltransferase