Cancers found specifically in women are often linked by one factor, a hormone group called oestrogens. In fact, there are three slightly different oestrogens found in women (and to a much lesser extent in men as well). These are oestradiol (E2), oestrone (E1) and oestriol (E3). They are produced originally from cholesterol (see Figure 7.1), and are, therefore, fat-based (or lipid-based) hormones known as steroids. Another female hormone, called progesterone, is also produced in the same sequence from cholesterol. In women the oestrogens are produced mostly in the ovaries, with smaller quantities being produced by the adrenal cortex (and that is why men also have small quantities of oestrogens, i.e. they also have adrenal glands, each with a cortex). Oestradiol (E2) is the most potent of the estrogens, and the one that has the greatest physiological effects. The potency of E2 is twelve times that of oestrone, and eighty times that of oestriol. This hormone promotes development of the female reproductive tract during the embryonic stages, and breast development during puberty. It continues to have a major influence throughout life, promoting cell division and maintaining health of the reproductive tissues. Oestrogen binds to oestrogen receptors (ER) within the cell (possibly inside the nucleus) and cells that have these
receptors are said to be ER positive (ER). On binding to the receptor, E2 forms a complex with receptors, and this complex then binds to a gene promoter region on the DNA (see Figure 7.2). The binding of a second oestradiol-receptor complex to the same promoter site (two E2ER complexes together is called a dimer) initiates gene promotion, i.e. it sets into motion the activation of the gene so that protein synthesis will commence (also known as gene expression). The genes that are switched on in this way are first, not surprisingly, a gene that replaces the original ER, otherwise the cell would use up all the ER and become ER negative (ER), i.e. no longer able to respond to E2. But, other genes are activated, including those that code for PgR (the progesterone receptor), and various growth hormones (see p. 36 and Figure 7.2). The other oestrogens are less important. E1 (oestrone) is held in the body mostly in an inactive form bound to the protein albumin in the blood. It also stimulates breast cell growth but to a lesser extent than E2. It becomes a more important oestrogen in women after the menopause, when levels of E2 drop. E3 (oestriol) is the weakest of the oestrogens (as a comparison, E2 has a thousand times greater effect on breast tissue than E3). In fact, E3 may have a beneficial effect on the prevention of breast cancer by occupying ER instead of E2. E3 is the form in which much of the oestrogen is excreted from
the body. The importance of understanding the nature of the oestrogens becomes apparent in the subject of breast cancer.