Characterisation of oestrogenic properties of Isoflavones derived from Millettia griffoniana Baill. [Elektronische Ressource] : molecular mode of action and tissue selectivity / vorgelegt von Germain Jean Magloire Ketcha Wanda

Christiane.Kubitz

Sujets

• Gesundheit

Informations

• Publié par: technische_universitat_dresden
• Publié le: 01 janvier 2006
• Nombre de lectures: 31
• Langue: Deutsch
• Poids de l'ouvrage: 1 Mo

Extrait

Characterisation of oestrogenic properties of
Isoflavones derived from Millettia griffoniana Baill.:
-Molecular mode of action and tissue selectivity





Dissertation


zur Erlangung des akademischen Grades
Doktor rerum naturalium (Dr. rer. nat.)
Der Fakultät Mathematik und Naturwissenschaften
der Technischen Universität Dresden


vorgelegt von
M.Sc. Germain Jean Magloire Ketcha Wanda
aus Bantoum I, Kamerun


eingereicht am 12.05.2006


Gutachter: Prof. Dr. habil. Günter Vollmer
Prof. Dr. habil. Herwig O. Gutzeit
Priv. Dz. Dr. habil. Patrick Diel


Datum der Verteidigung: 20.07.2006







































Gedruckt mit der Unterstützung des Deutschen Akademischen Austauschdienstes
(DAAD)
Dedication
















I dedicate this work to:
- My wife Bergeline Tchangoue Epouse Ketcha
- Borell Njonkoe Ketcha
- Loic Vianney Towa Ketcha Astrid Owona





Table of contents

Table of contents
Table of contents.................................................................................................................i
List of tables .......................................................................................................................v
List of figures .....................................................................................................................v
List of abbreviations...................................................................................................... viii
Summary ............................................................................................................................x

1 Introduction...1
1.1 current state of knowledge .................................................................................................... 1
1.2 Aim of the study.................................................................................................................... 2
1.3 Approach to the study..... 3
1.4 Thesis outline ........................................................................................................................ 3

2 Background and literature review ................................................................................5
2.1 Oestrogens............................................................................................................................. 5
2.1.1 Synthesis of oestogens..................................................................................................................5
2.1.2 Endogenous sources of oestrogens ...............................................................................................6
2.1.3 Transport and metabolism of oestrogens......................................................................................7
2.2 Physiological actions of oestrogens ...................................................................................... 7
2.2.1 Actions on the female reproductive system..7
2.2.2 Oestrogenic effects on the cardiovascular system ........................................................................8
2.2.3 Effects on bone.............................................................................................................................8
2.3 Oestrogen receptors............................................................................................................... 9
2.3.1 Discovery of oestrogen receptors........9
2.3.2 Structural and functional domains of oestrogen receptors..........................................................10
2.3.3 Distribution of oestrogen receptors ............................................................................................11
2.3.4 Regulation of oestrogen receptors ..............................................................................................12
2.4 Mechanism of Action of oestrogens.................................................................................... 13
2.4.1 Classical gene regulatory pathway (for oestrogen action)13
2.4.1.1 Oestrogen Response Element .............................................................................................13
2.4.1.2 Coactivators and corepressors of oestrogen receptors ........................................................14
2.4.2 ERE-independent pathways........................................................................................................15
2.4.2.1 AP-1 pathway .....................................................................................................................15
2.4.2.2 SP1 pathway .......................................................................................................................16
2.4.2.3 NF- κB pathway...................................................................................................................16
2.4.3 Non genomic pathway................................................................................................................17
2.4.3.1 Phosphatidylinositol 3-kinase (PI3K)-Akt Pathway ...........................................................17
2.4.3.2 Mitogen activated protein kinase (MAPK) pathway18
2.4.4 Oestrogen-independent pathways...............................................................................................18
2.5 Oestrogen antagonists or antiestrogens............................................................................... 19
2.5.1 Selective oestrogen receptor modulator (SERM) .......................................................................19
2.5.2 Pure oestrogen antagonists/ antioestrogens.20
2.6 Oestrogen disruptors/environmental oestrogens ................................................................. 21
2.6.1 “Xeno-oestrogens” .....................................................................................................................21
2.6.2 Synthetic oestrogens...................................................................................................................21
2.6.3 Phytoestrogens............................................................................................................................21
2.6.3.1 Isoflavones..........................................................................................................................22
i Table of contents

2.6.3.2 Flavonoids...........................................................................................................................23
2.6.3.3 Lignans ...............................................................................................................................23
2.6.3.4 Coumestans............23
2.7 Millettia griffoniana ............................................................................................................ 24
2.7.1 Botanical studies/distribution .....................................................................................................24
2.7.2 Description of plants of the genus Millettia................................................................................24
2.7.3 Phytochemistry/active constituents ............................................................................................24
2.7.4 Traditional use and application of Millettia griffoniana .............................................................25
2.8 Oestrogen-responsive genes used as marker genes 25
2.8.1 Cytochrom C oxidase (1A).........................................................................................................25
2.8.2 Proliferating cell nuclear antigen (PCNA)..................................................................................26
2.8.3 Ki-67...........................................................................................................................................26
2.8.4 Cyclin D1 (CD1) ........................................................................................................................26
2.8.5 Complement component 3 (C3)..................................................................................................26
2.8.6 Calcium binding protein 9 kilo Dalton (CaBP 9kD) ..................................................................27
2.8.7 Progesterone receptor (PR).........................................................................................................27
2.8.8 Vascular endothelial growth factor (VEGF) and VEGF-receptor 2 (VEGFR-2) .......................27
2.8.9 Clusterin (CLU)................28
2.8.10 Cyclooxygenase 2 (COX 2)......................................................................................................28
2.8.11 Insulin like growth factor 1 (IGF-1) .........................................................................................29
2.8.12 Insulin like growth factor binding protein 1 (IGFBP-1)...........................................................29
2.8.13 Carbonic anhydrase 2 (CA 2) ..........................................................................................