The metabolism of adrenal 11beta-hydroxyprogesterone, 11keto-progesterone and 16alpha-hydroxyprogesterone by steroidogenic enzymes

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dc.contributor.advisorSwart, Amanda C.en_ZA
dc.contributor.advisorSwart, Pieteren_ZA
dc.contributor.authorVan Rooyen, Desmareen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Biochemistry.en_ZA
dc.date.accessioned2017-02-21T19:36:10Z
dc.date.accessioned2017-03-29T20:59:04Z
dc.date.available2017-06-30T03:00:05Z
dc.date.issued2017-03
dc.descriptionThesis (MSc)--Stellenbosch University, 2017.en_ZA
dc.description.abstractENGLISH ABSTRACT: This study describes ■ Cytochrome P450 11β-hydroxylase (CYP11B1) and cytochrome P450 aldosterone synthase (CYP11B2) both catalyse the 11β-hydroxylation of progesterone (P4) to 11β-hydroxyprogesterone (11OHP4). ■ the 11β-hydroxylation of 16α-hydroxyprogesterone (16OHP4) catalysed by CYP11B2 only yielding 4-pregnen-11β,16α-diol-3,20-dione (11,16diOHP4). ■ Both 5α-reductase isozymes 1 and 2 (SRD5A1 and SRD5A2) catalyse the reduction of 11OHP4, 11keto-progesterone (11KP4), 16OHP4 and 11,16diOHP4 to 5α-pregnan-11β- ol,3,20-dione (11OH-DHP4), 11keto-dihydroprogesterone (11K-DHP4), 5α-pregnan-16α- ol,3,20-dione (16OH-DHP4) and 5α-pregnan-11β,16α-diol-3,20-dione (11,16diOH-DHP4). ■ AKR1C2 catalyses the 3α-reduction of 11OH-DHP4, 11K-DHP4 and 16OH-DHP4 2 to 3α,11β- dihydroxy-5α-pregnan-20-one (3,11diOH-DHP4), 5α-pregnan-3α-ol-11,20-dione (alfaxalone) and to 3α,16α-dihydroxy-5α-pregnan-20-one (3,16diOH-DHP4). ■ Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) catalyses the metabolism of alfaxalone to 11keto-androsterone (11KAST) –converting a C21 steroid to a C19 androgenic steroid. ■ 11OHP4 and 11KP4 are metabolised in the LNCaP cell model. 11OHP4 was metabolised to 11KP4, 11K-DHP4, alfaxalone and 11keto-dihydrotestosterone (11KDHT) while 11KP4 was metabolised to 11K-DHP4, alfaxalone and 11KDHT. ■ the activation of the androgen- and progesterone receptors by 11OHP4, 11KP4, 16OHP4 and their 5α-reduced metabolites.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Hierdie studie beskryf ■ Beide sitochroom P450 11β-hidroksilase (CYP11B1) en sitochroom P450 aldosteroon sintase (CYP11B2) kataliseer die 11β-hidroksilasie van progesteroon (P4) na 11β-hidroksieprogesteroon (11OHP4). ■ die 11β-hidroksilasie van 16α-hidroksieprogesteroon (16OHP4) gekataliseer deur slegs CYP11B2 na 4-pregnen-11β,16α-diol-3,20-dioon (11,16diOHP4). ■ Beide 5α-reduktase isosieme 1 en 2 (SRD5A1 en SRD5A2) kataliseer die reduksie van 11OHP4, 11ketoprogesteroon (11KP4), 16OHP4 en 11,16diOHP4 na 5α-pregnan-11β-ol,3,20- dioon (11OH-DHP4), 11keto-dihidroprogesteroon (11K-DHP4), 5α-pregnan-16α-ol,3,20-dioon (16OH-DHP4) en 5α-pregnan-11β,16α-diol-3,20-dioon (11,16diOH-DHP4). ■ AKR1C2 kataliseer die 3α-reduksie van 11OH-DHP4, 11K-DHP4 en 16OH-DHP4 na 3α,11β- dihidroksi-5α-pregnan-20-oon, 5α-pregnan-3α-ol-11,20-dioon (alfaksaloon) en na 3α,16α- dihydroksi-5α-pregnan-20-oon. ■ Sitochroom P450 17α-hidroksilase/17,20-liase (CYP17A1) kataliseer die metabolisme van alfaksaloon na 11ketoandrosteroon (11KAST) -die omskakeling van ‘n C21 steroїed na ‘n C19 androgeniese steroїed. ■ 11OHP4 en 11KP4 is gemetaboliseer in die LNCaP-sel model. 11OHP4 was gemetaboliseer na 11KP4, 11K-DHP4, alfaksaloon en 11keto-dihydrotestosterone (11KDHT) terwyl 11KP4 gemetaboliseer was na 11K-DHP4, alfaksaloon en 11KDHT., as bewys vir die metabolisme van C11-oksie C21 steroїede in die “agterdeur” padweg tot aktiewe androgene. ■ die aktivering van die androgeen- en progesteroon reseptore deur 11OHP4, 11KP4, 16OHP4 sowel as hul 5α-gereduseerde metaboliete.af_ZA
dc.embargo.terms2017-06-30
dc.format.extent144 pages : illustrationsen_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/101421
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subjectAdrenal 11 beta-hydroxyprogesterone -- Metabolismen_ZA
dc.subjectAdrenal 11 keto-progesterone -- Metabolismen_ZA
dc.subjectAdrenal 16 alpha-hydroxyprogesterone -- Metabolismen_ZA
dc.subjectSteroidogenic enzymesen_ZA
dc.subjectUCTDen_ZA
dc.titleThe metabolism of adrenal 11beta-hydroxyprogesterone, 11keto-progesterone and 16alpha-hydroxyprogesterone by steroidogenic enzymesen_ZA
dc.typeThesisen_ZA
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