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Oestrogen receptor: structure

The oestrogen receptor belongs to the steroid

receptor superfamily, which comprises the

glucocorticoid, vitamin D, thyroid hormone,

androgen, and retinoid receptors-whose

modular construction with its highly

conserved DNA-binding domains bespeaks a

common evolutionary origin for these

complex proteins.3 (See Fig. 12.2.)

The receptors reside in the nucleus,

cloaked by heatshock proteins (HSP) until the

arrival of ligand. Physiologically, ligand is

usually oestradiol or oestrone which is

incorporated into the large binding cavity of

the oestrogen receptor (ER), thereby

triggering conformational change as the

activated receptor dimerizes, casts off the

HSP, and displays binding sites for a range of

co-activators and co-repressors that modulate

its subsequent activity.4 (See Fig. 12.3.)

The oestrogen-ER complex now seeks the

palindromic promotor sequences of oestrogen

response elements in target genes. The

complex then proceeds to facilitate RNA

transcriptase and messenger RNA. An

essential feature of ER action is the differential

activity of the transcriptase activation areas

AF-1 is thought to be constitutive, that is,

it operates without the presence of ligand,

whereas AF-2 requires the presence of

oestradiol or a substitute in the binding cavity

of the receptor.