Research Article Details

Article ID: A06140
PMID: 32991990
Source: J Steroid Biochem Mol Biol
Title: Involvement of endogenous testosterone in hepatic steatosis in women with polycystic ovarian syndrome.
Abstract: AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in women with polycystic ovarian syndrome (PCOS) than that in healthy women. This association can be explained in part by the resistance to insulin and the prevalence of obesity, which are fueled by high androgen levels. However, there is little evidence of the involvement of endogenous testosterone in hepatic steatosis in women with PCOS. Here, we treated Sprague Dawley rats with the aromatase inhibitor, letrozole, to increase the endogenous testosterone level and to decrease the estradiol levels. We also quantified the testosterone levels in human serum specimens and HepG2 cells to investigate the effects of androgens on hepatic steatosis and liver dysfunction. RESULTS: Twenty-nine PCOS patients and twenty healthy women were enrolled. Alanine transaminase and aspartate transaminase (AST) levels were increased in women with PCOS, and a strong correlation between testosterone and AST levels was observed. After letrozole treatment for 90 days, rats were significantly more obese, with animals developing hepatic steatosis and moderate insulin resistance. Additional experiments revealed that excess androgen inhibited the AMP-activated protein kinase alpha pathway in letrozole-treated livers and dihydrotestosterone (DHT)-treated HepG2 cells, thereby causing steatosis. INNOVATION AND CONCLUSION: Our results show that an elevated endogenous testosterone level can induce hepatic steatosis. Decreasing the endogenous testosterone level in hepatocytes may represent a new approach in the treatment of NAFLD in PCOS patients.
DOI: 10.1016/j.jsbmb.2020.105752

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name

Diseases ID DO ID Disease Name Definition Class
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details
I14 9970 Obesity An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D199 L-alanine Chemical drug DB00160 KYNU -- Failed in clinical trials Details
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D476 Estradiol Chemical drug DB00783 -- -- Under clinical trials Details