The Possible Effect of DHEA on Hepatic and Metabolic Dysfunction in a Rat Model of Male Hypogonadism

Abstract Background: Male hypogonadism is characterized by androgen deficiency in the body. Several studies have shown that testosterone deficiency is inducing a metabolic syndrome and insulin resistance. Although of the unwanted effects of exogenous testosterone replacement therapy, it is the main treatment of male hypogonadism. One of the safe treatment options is Dehydroepiandrosterone (DHEA) replacement therapy which is the precursor of testosterone. Up to date and to the best of our knowledge, no one investigates the effect of DHEA on glucose-6-phosphatase enzyme in a rat model of male hypogonadism and its impact on the metabolic dys-function. Aim of Study: The aim of the research is to investigate the possible protective effect of DHEA on hepatic and meta-bolic dysfunction in a rate model of male hypogonadism through examining its effect on glucose-6-phosphatase enzyme. Moreover, it studies the possible therapeutic effects of the male androgen (DHEA) on the hepatic steatosis and insulin resistance triggered by testosterone deficiency. Material and Methods: Thirty-two Wistar Kyoto rats were divided into 4 groups as follows (I) Untreated controls, (II) Untreated orchidectomized, (III) Control, treated with DHEA and (IV) Orchidectomized, treated with DHEA. Treatment was carried three times per week for 12 weeks. Cobas c111, Roche diagnostic, USA machine was used to measure the level of the glucose, liver enzymes and lipid profile. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure the plasma level of testosterone hormone, insulin and glucose-6-phosphatase enzyme. Results: As expected, the plasma testosterone decreased significantly in ORCH rats, with significant increase in glucose, lipid profile as well as significant decrease in insulin as compared to control rats. Moreover, our data revealed insig-nificant increases in plasma testosterone in ORCH + DHEA with significant increase in ORCH + DHEA compared to control + DHEA. DHEA did not significantly affect G-6-Pase enzyme. Also, ORCH shows significant increase in triglyceride and cholesterol as well as the ORCH + DHEA.
Conclusion: Testosterone deficiency and DHEA replace-ment therapy have no effects on glucose 6-phosphatase enzyme. Male hypogonadism is a risk factor for metabolic syndrome and NAFLD that could not be treated effectively with DHEA.