Fundamental aspects of oestrogens: intracellular receptors and gene activation.

The steroid hormones exert their biological responses through a multi-step process involving regulation of gene expression. The hormone passes across the target-cell membrane from the circulation and enters the cytoplasm where it binds to a specific protein designated the receptor. A conformational change in the receptor ensues and the receptor-hormone complex is translocated to the chromatin in the cell nucleus. Interaction of the receptor-hormone complex with specific regions of the DNA and with specific non-histone chromatin proteins leads to initiation of transcription of new molecules of RNA. The primary RNA transcripts are processed to give mature molecules of messenger-RNA which are transported to the cytoplasm where they combine with ribosomes to form polysomes. The messenger-RNA is translated, by the cytoplasmic machinery of protein synthesis, into various new proteins. These proteins then promote the well-established biological responses associated with each particular steroid. Impairment of any of these steps (for example, lack of production of steroid, absence of receptor, a defect in structure of the receptor) results in a disturbance in or loss of the normal biological response.