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Changes in plasma oestradiol levels with oestrogen deprivation. ? Fulvestrant. 3rd gen AIs. 1st/2nd gen AIs. OvX/GnRHa. Premeno. Postmeno. 10. 1. 1000. 100. Plasma oestradiol levels (pmol/L). Anatomy of the Breast. Blood Supply to the Breast. AF1. AF1. AF1. AF1. E. E. E. E.
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Changes in plasma oestradiol levels with oestrogen deprivation ? Fulvestrant 3rd gen AIs 1st/2nd gen AIs OvX/GnRHa Premeno Postmeno 10 1 1000 100 Plasma oestradiol levels (pmol/L)
AF1 AF1 AF1 AF1 E E E E AF2 AF2 Effects of oestrogen on transcription ofoestrogen responsive genes transcription co-act H S P ER loss of HSPs phosphorylation, dimerisation conformational change + E transcription co-act
Effects of tamoxifen on transcriptionof oestrogen responsive genes transcription co-act AGONISM AF1 AF1 T T AF2 loss of HSPs phosphorylation, dimerisation conformational change H S P ER + T no transcription AF1 AF1 ANTAGONISM T T co-act AF2
Oestrogen receptor function – 2003 P P P P P AIB1 ER P ERK1,2, AKT, JNK, P38, IKK
Premenopausal oestrogen production Gonadotrophins (FSH + LH) ‘Zoladex’ Oestrogens Ovary Tamoxifen Pituitary gland Adrenal glands LHRH (hypothalamus) Androgens Oestrogens ACTH Anastrozole Peripheral conversion (aromatase enzyme) ACTH = adrenocorticotrophichormone;FSH = follicle-stimulating hormone;LH = luteinising hormone;LHRH = LH-releasing hormone