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The influence of Rooibos (Aspalathus linearis) on adrenal steroidogenic P450 enzymesPerold, Helene 03 1900 (has links)
Thesis (MSc (Biochemistry))--University of Stellenbosch, 2009. / This study:
1. Describes the preparation of unfermented and fermented rooibos methanol and aqueous
extracts.
2. Investigates the influence of unfermented and fermented rooibos methanol and aqueous
extracts on the binding of natural steroid substrates to ovine adrenal microsomal
cytochrome P450 enzymes, demonstrating that the binding of natural steroids is inhibited
in the presence of rooibos extracts.
3. Describes an assay demonstrating the inhibitory effect of rooibos extracts on the catalytic
activity of cytochrome 17α-hydroxylase (CYP17) and cytochrome 21-hydroxylase
(CYP21) in ovine adrenal microsomes.
4. Investigates the influence of unfermented and fermented rooibos methanol extracts on the
catalytic activity of individual cytochrome P450 enzymes – CYP17 and baboon CYP21,
that are expressed in COS1 cells.
5. Demonstrates that fractions of the unfermented rooibos methanol extract inhibits the
binding of natural steroid substrate to microsomal cytochrome P450 enzymes as well as
the catalytic activity of baboon CYP21 expressed in COS1 cells.
6. Investigates the inhibitory influence of individual rooibos flavonoids on the catalytic
activity of baboon CYP21 expressed in COS1 cells.
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Enzymatic Regulation of Steroidogenesis and Nuclear Receptor Activation : Special Focus on Vitamin D and Sex HormonesLundqvist, Johan January 2011 (has links)
Enzyme-catalyzed reactions are important to regulate steroidogenesis and nuclear receptor activation. The present investigation examines the role of steroid metabolism catalyzed by CYP7B1 for regulation of hormone receptor activation and the effects of vitamin D on enzymatic regulation of steroidogenesis. The study reports data indicating that CYP7B1 can regulate estrogenic signaling by converting estrogens into inactive or less active metabolites. Similar results were obtained for CYP7B1-mediated metabolism of some androgen receptor ligands, indicating that CYP7B1 can be involved also in the regulation of androgenic signaling. CYP7B1 substrates and metabolites were found to exert androgenic effects in a cell line-specific manner. Furthermore, cell line differences were observed in the expression pattern for androgen receptor comodulators. This thesis reports that 1α,25-dihydroxyvitamin D3 alters the gene expression and enzyme activity of CYP21A2 and CYP17A1 leading to suppressed production of aldosterone, dehydroepiandrosterone and androstenedione in adrenocortical cells. These are novel findings on vitamin D action. A mechanism is reported for the vitamin D-mediated regulation of the CYP21A2 gene. Data indicate that vitamin D receptor interacting repressor (VDIR) and Williams syndrome transcription factor (WSTF) are key comodulators in this novel vitamin D receptor (VDR)-mediated mechanism. Furthermore, the results indicate that altered expression levels of VDIR and WSTF can shift the suppressing effect of vitamin D to a stimulatory effect. Also, epigenetic components were found to be involved in the effects of vitamin D on CYP21A2 transcriptional rate. In addition, a functional vitamin D response element was identified in the CYP21A2 promoter. This study also reports that 1α,25-dihydroxyvitamin D3 affects sex hormone production in a tissue-specific way. Gene expression and enzyme activity of aromatase were found to be downregulated in cells derived from breast, but not in cells derived from prostate and adrenal cortex. The production of estradiol and dihydrotestosterone was altered in a tissue-selective manner following vitamin D treatment. These findings are of importance for the discussion on vitamin D as a potential anti-breast cancer agent.
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