Testosterone and estradiol are the principle hormones which control the sexual characteristics of males and females, respectively. They are both steroids, that is they are based upon the general pattern of the 17-carbon ring system shown below. This is the same structure used by other biologically important steroid molecules, including drugs, poisons, bile acids, vitamins and hormones. Examples are cortisone (which controls carbohydrate metabolism and is used therapeutically to relieve symptoms of inflammation), Vitamin D2 (which is essential for calcium metabolism and prevents rickets), digitoxigenin (which is extracted from the digitalis plant and used to regulate heart rates), cholesterol (which forms part of all cell membranes), and many others.
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| The steroid structure. The ring carbons are numbered 1 to 17, and the 4 rings are labelled A-D as indicated. Side chain carbons are numbered from 18 upwards. The biological activity of the different steroids depends on the nature of the substituents attached to this basic structure, and even slight changes can dramatically alter the biological effect of the molecule. |
The steroid hormones are mostly non-polar molecules that can readily pass through cell membranes. They work by entering the cell and binding to a receptor site on a large protein molecule. This steroid-receptor unit is then transferred to the nucleus of the cell where it activates specific genes. This means that steroid hormones create effects over a much slower timescale (hours or days) than those of other non-hormonal steroids (such as cortisone, digitoxigenin, etc), which instead act on the surface of the cell membrane and cause effects almost instantly.
One of the results of puberty in boys is the initiation of testosterone secretion from special cells within the testes. This then controls the development of all the masculine secondary sexual characteristics, such as an enlargement of the skeleton, deepening of the voice, the growth and pattern of body hair, and maturation of the sexual organs. It has also been linked to changes in behaviour patterns, particularly those involving heightened aggression and competitiveness.
 | Testosterone - the male hormone |
Anabolic steroids are illegal drugs popular among athletes in sports that require muscle building and strength. The term comes from anabolism, which is the scientific term for protein formation. The most commonly used anabolic steroid is just testosterone, which is the hormone primarily responsible for the greater muscle mass of men than women. Many athletes, both men and women, have taken this drug to increase muscle development, despite the potential for serious medical side effects. Because testosterone is not very effective when taken orally, it must be injected for best results. This has encouraged scientists to develop synthetic anabolic steroids, based on the testosterone structure, that can be taken orally. One of these 'designer steroids', stanozolol, was found in the urine of Canadian sprinter Ben Johnson after he won the 100 metre race in the 1988 Olympics, causing him to be banned from competition for several years.
The main female hormones are known collectively as oestrogens. There are a number of these, all of which have a similar structure, examples of which include estradiol and estrone. They differ from testosterone only slightly, by having one less -CH3 group at the 19-carbon position, the C=O group at the C-3 position being reduced to -OH, and the A-ring being fully delocalised. It is amazing to realise that these slight changes in molecule structure are all that differentiates male from female!
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| Estradiol | Estrone |
The main female hormones. Differences between the two are highlighted in red, and the difference between them and testosterone are shown in blue.
As with testosterone in boys, these hormones are released at puberty in girls, and maintain the female secondary sexual characteristics throughout the woman's fertile life, until the menopause, whereupon their concentration decreases rapidly. They work by acting upon RNA, which, in turn, controls how the instructions in DNA concerning growth are to be interpreted.
Another female hormone is progesterone, which, again, is very similar in structure to the oestrogenic steroids. Its function, however, is slightly different, in that it is involved in the preparation for and the maintenance of pregnancy. It does this by suppressing ovulation (since the release of more eggs isn't required if the woman is already pregnant), initiating milk production and by promoting the growth of mucus in the womb. Again, it is strange to realise that this very female hormone is identical in structure to the male testosterone molecule, except for the acetylation of the -OH group on C-17.
| Progesterone - the pregnancy hormone. The changes from testosterone are highlighted in red. |
During the female menopause, the ovaries begin producing far less oestrogenic hormones, which in turn affects the complex balance of all the other hormones in the body. This can lead to problems such as an increase in weight, hot flushes and psychological problems. These symptoms can be alleviated by so-called 'hormone replacement therapy', which involves consumption of additional oestrogenic hormones which take the place of those no longer produced by the body. The hormone mixture usually contains a mixture of 3 hormones, estrone, equilin (which has the same structure as estrone except an extra double bond between carbons 5 and 10) and dihydroequilin (which is equilin with a -OH group replacing the C=O on carbon 3).
One of the most dramatic achievements of modern synthetic organic chemistry has been the development of "the pill". The development of this drug is arguably one of chemistry's greatest contributions to liberty, and has had a profound impact on the history and mores of human society. There are actually a number of different human contraceptives in use, and these are often a combination of an oestrogen and a progesterone. They work by maintaining the high levels of hormones that are normally present during pregnancy, thereby suppressing ovulation. One example of such a contraceptive pill is the synthetic steroid norethindrone (known by the tradename Norlutin), which closely resembles the progesterone structure, except for the addition of an acetylene group at the C-17 position. The structural changes from progesterone were required in order to make it possible for the drug to be taken orally, since pure progesterone is inactive when taken by mouth since it is rapidly metabolised in the liver.
| Norethindrone - the changes from progesterone are highlighted in red |