chapter  12
3 Pages

Selective oestrogen receptor modulators

ByDavid W Purdie, Clare E Kearney

If one accepts Gordhansky’s famous phrase

‘Nothing in biology makes sense except in

terms of evolution’, then the group of steroid

hormones known as the oestrogens have

indeed conferred survival advantage through

their involvement in many vertebrate

physiological systems. The simplest living

organism that has been shown to possess an

oestrogen receptor and oestradiol 17 as

ligand is the eukaryotic unicellular yeast

Saccharomyces cerevisiae.1 Among multicellular

animals the oestrogens are found first in the

phylum Echinodermata, represented today by

the starfish, and in the phylum Mollusca,

represented by the octopus and squid, whose

ancestors, evolving from simpler forms some

400 million years ago, were apparently the

first to possess the cytochrome P450

aromatase enzyme system necessary to convert

C-19 androgens to C-18 oestrogens.2 Studies

of steroid hormone evolution show that in

comparison the glucocorticoids and

mineralocorticoids are of more recent origin,

appearing first in the elasmobranchs-sharks

and rays-and that aldosterone is first found

in the teleosts or bony fish. When one

considers that it was only 6 million years ago

that the evolutionary line leading to Homo

sapiens branched away from the line leading to

our nearest cousin, Pan troglodytes, the

chimpanzee, it can be seen that our species

inherited a signalling system that had been

part of physiology for the major part of

eukaryotic life on earth. Nature is

parsimonious. A molecule that possesses a set

of physico-chemical characteristics that are of

advantage in a primitive system may be

retained to discharge its function in more

complex evolving systems provided that such

new functions do not confer a net

disadvantage upon survival.