The selective oestrogen receptor modulation: evolution and clinical applications

Steroids are widely dispersed throughout the biosphere where they fulfil a plethora of roles as bioregulators in both plants and animals. Indeed the s implest organism yet discovered to be utilizing them is a water mold which deploys a pheromone, oogoniol, which is a steroid. Within the animal kingdo m, true hormonal use of the oestrogens appears to be restricted to the phyl a Arthropoda and Chordata whereas their elaboration appears to have origina ted as early as approximate to 400 million years ago with the phyla Mollusc a and Echinodermata which developed the cytochrome P450(arom) necessary to convert androstenedione to oestrone and testosterone to oestradiol. Until r elatively recently it was assumed that, in the human, the endocrine oestrog ens were largely if not exclusively involved in reproductive physiology. Th ey were known to be responsible, with other agents, for the complex signall ing and signal transduction which prepares the female organism for the key events of ovulation, blastocyst implantation, maternal adaptation to pregna ncy and lactation-all of which, being central to the survival of the specie s, are highly conserved. However, the last half century has seen a major ex pansion in our understanding of the range of oestrogenic activity in physio logy. The physico-chemical characteristics of the oestrogens and their rece ptors provide a signal and signal transduction system of high utility which has found a role in many systems unrelated to reproduction.