steroids comprise a large group of substances that mediate a very varied set of biological responses. The most widespread in the body is
cholesterol, an essential component of
cell membranes, and the starting point for the synthesis of other steroids — the
sex hormones, adrenal cortical hormones, and the
bile salts.
The steroids are grouped together because their chemical structures are all very similar. The steroid chemical nucleus consists of four carbon rings, three 6-sided and one 5-sided, joined together by their edges. The specificity of their different biological actions is due to the various groups attached to a common nucleus. When alcohol groups (OH) are attached, steroids should properly be called
sterols (such as
cortisol), whereas ketone groups (C=O) make them
sterones (such as
aldosterone).
Different steroids react with different
membrane receptors in cells, and a precise fit between the steroid and the receptor is required. Therefore a single steroid can be expected to have a specific effect.
Steroids have major responsibilities as hormones, controlling
metabolism, salt balance, and the development and function of the sexual organs as well as other bodily differences between the sexes. Steroids in the form of bile salts assist in digestive processes, while another steroid is a vitamin that takes part in
calcium control.
Steroid hormones
Steroid hormones are made and secreted into the circulating blood by the cortex of the
adrenal glands and the gonads (testes or ovaries). Mostly, their secretion is regulated by hormones from the
pituitary gland, and those in turn by chemical messages from the
hypothalamus.
Two types of steroids are released from the adrenal cortex, the
glucocorticoids, mainly cortisol (hydrocortisone) and the
mineralocorticoids, mainly aldosterone. Both types of hormone are important in stress situations such as disease or
injury.
Glucocorticoids mobilize glucose, which is particularly important in fasting conditions. They do so by promoting glucose formation from non carbohydrate sources in the liver, increasing
glycogen levels, and raising the blood glucose concentration. Liberation of glucocorticoids from the adrenal cortex is caused by
adrenocorticotrophic hormone (ACTH), released from the pituitary gland. When the glucocorticoid level in the blood is low, ACTH is released, but when it is high the release of ACTH is suppressed. This is a good example, one of many that occur in the body, of a feedback system. Large doses of glucocorticoids are anti-inflammatory and at one time it was thought they would provide suitable treatment for inflammatory conditions such as rheumatoid arthritis. However, the excessive breakdown of proteins, mobilized to form glucose in the liver, leads to muscle weakness and osteoporosis and there is also ‘moon face’ and
obesity. This describes exactly the features of
Cushing's syndrome, a condition caused by excess secretion of corticosteroids. Furthermore, if therapy with glucocorticoids is withdrawn rapidly the pituitary system is so suppressed that the body's own system takes a while to trip in, leading to an ‘Addisonian crisis’, mimicking Addison's disease in which there is a deficiency in glucocorticoid production. With due precautions, however, corticosteroids remain a useful treatment in some severe allergic and inflammatory conditions.
The mineralocorticoid aldosterone is released at an increased rate from the adrenal glands if the body is salt depleted; this is stimulated by a complex detecting system in the
kidneys, resulting in an increase in circulating
angiotensin, which acts in turn on the adrenal glands. Aldosterone promotes sodium reabsorption by the kidneys, so that there is less salt in the urine, thus correcting the deficiency. It acts on sweat glands similarly, diminishing salt loss in sweat.
Male steroid sex hormones,
androgens, are produced in the testes. Testosterone is the most important of the androgens and is responsible for controlling the production and maturation of sperm, as well as male characteristics, such as the distribution of body hair.
Anabolic steroids are derivatives of testosterone and act on androgenic receptors. They build up muscle mass and cause virilization — features of masculinity. They are useful in the treatment of debilitated patients to help restore their physique. Unfortunately these substances have been taken illicitly by athletes for
body-building. Their use carries considerable risk, as sudden withdrawal will leave the body's natural processes suppressed, by interference with the feedback system as described above. Detection of the use of anabolic steroids has become difficult as it appears that one that is commonly used, namely
nandrolone, can be synthesized by the body itself in small quantities, especially when under physical stress. Female steroid sex hormones are of two types,
oestrogens and
progestins, both from the ovaries. Again under pituitary hormone regulation, their relative secretion varies within the menstrual cycle. Oestrogens promote the growth of the lining of the uterus in preparation for implantation of a fertilized egg. Once the egg has been shed from the ovary, the
corpus luteum (yellow body), which develops in the cavity left behind, secretes progesterone; this promotes further development of the uterine lining and, if implantation of an embryo occurs, maintains changes here and elsewhere for the duration of pregnancy.
The understanding of these processes is the basis of the contraceptive pill. Synthetic steroids were devised for this purpose, as natural steroids are metabolized by the liver if taken by mouth. As with the other steroid hormones, there are feedback systems involving the pituitary gland. Taking oestrogens inhibits the release from the pituitary of the
follicular stimulating hormone that would normally cause maturation of eggs in the ovary: so, no ovulation, no conception. Contraceptive pills usually contain both oestrogens and progestins, which are taken concurrently or sequentially during the 4 week course, menstruation following when the course ceases. A large dose of both an oestrogen and progestin promotes uterine bleeding within a few hours and is the basis of the ‘morning after’ pill.
Steroids and bile
Cholesterol, taken up from the blood into the liver or synthesized there, can be oxidized in the liver to cholic acid. Conjugation of this with taurine or glycine gives the bile salts,
taurocholate and
glycocholate. These bile salts pass into the small intestine and have important actions in aiding the digestion and absorption of fats. Cholesterol itself is excreted in the bile.
The steroid vitamin
Exposure to ultraviolet light converts a steroid,
dehydrocholesterol, in the skin to vitamin D. This is what happens when you sunbathe, but in climes where exposure to the sun is limited it is necessary to supplement the diet with the vitamin. Fish oils are rich in vitamin D and the Eskimo diet ensures that they get a sufficient supply. The vitamin primarily promotes calcium absorption from the gut. Calcium is essential for bone growth and maintenance, muscle contraction, and many signalling processes in the body.
While steroids have many different actions on the body, their mechanism of action is similar in all instances. The receptors for steroids are inside cells (unlike those for many other substances, which are on the cell membrane). The complex formed by combination of the steroid with its specific receptor enters the nucleus and switches on or off the appropriate genes, which then gives rise to the characteristic effect. Their actions are not therefore immediate as with, for example,
neurotransmitters, nor are they as rapid as those of the peptide hormones; several hours elapse before the effect appears. To give one example, the receptors for aldosterone are located in the end part of the kidney tubules. Here genes are switched on which lead to the synthesis of the molecules that actually handle the reabsorption of sodium ions from the urine back into the blood. The process becomes more efficient because there are a larger number of molecular entities dedicated to the task.
Alan W. Cuthbert
See also
bile;
body building;
hormones;
menstrual cycle;
sex hormones.
