Endokrin Bozucuların Steroidojenez Üzerine Etkilerinin Hormon Analizleri İle Belirlenmesi
Project no. 394 · Status: Kapanmış · 2014
Summary
Endocrine disruptors (EB) are defined as exogenous substances that cause adverse health effects and changes in endocrine functions in healthy organisms or in their future generations. EB can act as an agonist or antagonist by interacting with hormone receptors, or it can also exert its effects by changing physiological hormone levels by interacting with enzymes involved in the biosynthesis and metabolism pathways of steroid hormones. In this thesis study, in order to investigate the effects of endocrine disruptors on steroidogenesis, which is the synthesis pathway of sex hormones, a validated in vitro method specified in the OECD TG-456 test guide was applied in our laboratory and ELISA and LC MS/MS were used to determine estradiol (E2) and testosterone (T) levels as a result of the experiment. It is aimed to use the methods of analysis and to compare the data obtained by both analysis methods. Partial validation of the method(s) was made using forskolin as a positive control (enzyme inducing effect) as stated in the OECD guideline, prochlorase as a negative control (enzyme inhibitory effect), ketoconazole, letrozole and genistein, which are reference substances with known efficacy on E2 and T in the steroidogenesis cycle. measurement performances were compared. Whether there is a difference between the two methods was evaluated statistically. Subsequently, 2-Methyl-1-H-indole-3-carboxyaldehyde (4-chlorophenyl) hydrazone (M6) and 2-methylindole-3-carboxyaldehyde, which are newly synthesized drug active substance candidates, will be recommended to be used as an aromatase enzyme inhibitor in the treatment of hormone-dependent breast cancer. The effects of phenyl hydrazone (M20) and their model compound, melatonin, on the entire steroidogenesis pathway were also investigated after the application of the H295R steroidogenesis method, by performing hormone analyzes with both methods. As a result, the two methods applied were evaluated in terms of advantages and disadvantages.