Impact of Androgen and Dietary Advanced Glycation End Products on Female Rat Liver

Abstract

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 (γGT) (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 γGT 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.

Impact of Body Mass Index on Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection Among Polycystic Ovarian Syndrome Patients

“…Higher level of insulin resistance and compensatory hyperinsulinaemia contribute to hyperandrogenism in PCOS and leads to the increase of T [35], arresting folliculogenesis through inhibition of granulosa cell proliferation and maturation, oestrogen and progesterone secretion and leading to anovulatory infertility [36]. A previous study on female rats revealed that androgen level may play an important role in liver metabolism and triglycerides level was also elevated in androgenized prepubertal rats compared to non-androgenized rats [37], which may provide a clue about the correlation between PCOS and obesity. In this study, we found that the basal levels of FSH and LH were significantly reduced in obese non-PCOS patients.…”

Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to Low Plasma Nitric Oxide in Polycystic Ovary Syndrome

“…The high levels of androgen and advanced glycation end products (AGEs) in PCOS women induces oxidative stress and inflammation [3]. Recent reports showed strong involvement of oxidative stress [4, 5] and endothelial dysfunction [6-8] in PCOS pathogenesis.…”

MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease

“…Jones et al compared several metabolic parameters in PCOS women with and without AE diagnosed according to the Rotterdam criteria and found that liver fat was significantly higher in hyperandrogenic PCOS compared to normoandrogenic PCOS women (diagnosed with PCOS due to PCO + AO), even after adjustment for obesity, IR and visceral and intra-abdominal fat (152). Androgenised female rats fed with a diet rich in advanced glycation end products have been shown to develop deranged hepatic function (153). However, putative causative mechanisms underlying PCOS-related NAFLD remain to be elucidated.…”