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Browsing by Subject "testosteroni"

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  • Turunen, Iida (2023)
    Metastatic prostate cancer is often fatal disease stage. Mechanism causing prostate cancer remains unknown, but possible mechanism relies on hormones. Testosterone may activate spontaneous cell division of oncogenes. Prostate cancer cells require androgen cell stimulation of AR to grow in early stages of prostate cancer, approximately 80-90% of prostate cancer cases are androgen dependent. 3bHSD1, encoded by HSD3B1, catalyzes the conversion of dehydroepiandrosterone to androstenedione and further to T and DHT. SNP (1245A to C) in HSD3B1 changes asparagine to threonine in position 367 resulting the enzyme accumulation and increased function. With androgen deprivation therapy castrate levels of testosterone are often achieved and it induces positive response in most PCa patients, but the polymorphism of 1245C is related with lower survival rate and higher probability for PCa to develop into CRPC. The aim of this study was to find out the effect of SNP in 3bHSD1 to androgen levels in patients treated with ADT. 32 patients were first genotyped based on SNP in the HSD3B1 gene (rs1047303) with 96.9 % success rate. 21 patients represented genotype AA, 9 AC and 1 patient CC. Other mutation in rs6203 was also detected. Genotyping was done by isolating DNA from blood samples and preparing it further for Sanger sequencing. Steroid analysis was performed by using LC/MS, using liquid-liquid extraction as sample preparation method. Altogether 21 steroids were analyzed from serum samples. Samples were taken every 3 months, during 33 months period for longest. The concentrations of T and DHT were reduced in AA genotype group after ADT as was expected to happen in all of the groups. In fact, the only significant changes were seen in AA genotype with for example the concentrations of previously mentioned T, DHEA and also A4. The changes in measured androgen levels cannot be generalized to concern especially the CC genotype, as there was only one patient homozygote with the mutation. Even though these results gave promising data of possible androgen synthesis pathways, a similar study must be rerun with larger patient data to be sure of the characteristics of different genotypes. Also, the effect of SNP in rs6203 remains still unknown.
  • Valkonen, Minna (2013)
    The aim of this work was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for imitation of phase I metabolism of selected anabolic steroids. The role of the solvent composition and the time of UV exposure in the TiO2 photocatalysis were also investigated. TiO2 photocatalysis has been reported to produce mainly the same phase I reaction types formed in drug metabolism in vitro and in vivo. The selected anabolic steroids were testosterone, methyltestosterone, metandienone, nandrolone and stanozolol. Products from TiO2 photocatalysis were compared to products formed in microsomal incubations (HLM). Comparison was made on the basis of same mass, retention time and similarity of the product ion spectra. The samples were analyzed with ultra performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (Q-TOF). Electrospray ionization (ESI) in positive ion mode was used for ionization and product ion scan with two different collision energy was used for collision induced dissociation of the steroids and the reaction products. TiO2 photocatalysis is a simple and fast method. For all the steroids studied, the main reactions observed both in TiO2 photocatalysis and microsomal incubations were dehydrogenation, hydroxylation and combination of these two. Several isomers with same mass and retention time were formed. In addition, dihydroxylation and dihydroxylation+dehydrogenation products of stanozolol were observed both in TiO2 photocatalysis, but these were different isomers in different systems. In most cases the product ion spectra of isomers with same retention time were similar but the weak intensity of some peaks caused uncertainty in the interpretation of spectra. TiO2 photocatalysis might be useful in fast screening of possible drug metabolites. However the feasibility of TiO2 photocatalysis needs to be further studied because the differences in stereochemistry in TiO2 photocatalysis and microsomal incubations. If TiO2 photocatalytic reactions can be scaled up, it might be possible to produce standard compounds for example for doping laboratories.