11.6: Steroids
- To identify the functions of steroids produced in mammals.
Triglycerides are saponifiable. That means triglycerides can react with aqueous base (alkali) to yield simpler components, such as glycerol and fatty acid salts (soap). Lipid samples extracted from cellular material, however, also contain a small but important fraction that does not react with alkali. Such a lipid is non saponifiable. The most important nonsaponifiable lipids are the steroids. These compounds include the bile salts , cholesterol, and certain hormones (such as cortisone and the sex hormones).
Steroids occur in plants, animals, yeasts, and molds but not in bacteria. They may exist in free form or combined with fatty acids or carbohydrates. All steroids have a characteristic structural component consisting of four fused rings. Chemists identify the rings by capital letters and number the carbon atoms as shown in Figure \(\PageIndex{1a}\). Slight variations in this structure or in the atoms or groups attached to it produce profound differences in biological activity.
Cholesterol
Cholesterol (Figure \(\PageIndex{1b}\)) does not occur in plants, but it is the most abundant steroid in the human body (240 g is a typical amount). Excess cholesterol is believed to be a primary factor in the development of atherosclerosis and heart disease, which are major health problems in the United States today. About half of the body’s cholesterol is interspersed in the lipid bilayer of cell membranes. Much of the rest is converted to cholic acid, which is used in the formation of bile salts. Cholesterol is also a precursor in the synthesis of sex hormones, adrenal hormones, and vitamin D.
Excess cholesterol not metabolized by the body is released from the liver and transported by the blood to the gallbladder. Normally, it stays in solution there until being secreted into the intestine (as a component of bile) to be eliminated. Sometimes, however, cholesterol in the gallbladder precipitates in the form of gallstones (Figure \(\PageIndex{2}\)). Indeed, the name cholesterol is derived from the Greek chole , meaning “bile,” and stereos , meaning “solid.”
Heart disease is the leading cause of death in the United States for both men and women. The Centers for Disease Control and Prevention reported that heart disease claimed 631,636 lives in the United States (26% of all reported deaths) in 2006.
Scientists agree that elevated cholesterol levels in the blood, as well as high blood pressure, obesity, diabetes, and cigarette smoking, are associated with an increased risk of heart disease. A long-term investigation by the National Institutes of Health showed that among men ages 30 to 49, the incidence of heart disease was five times greater for those whose cholesterol levels were above 260 mg/100 mL of serum than for those with cholesterol levels of 200 mg/100 mL or less. The cholesterol content of blood varies considerably with age, diet, and sex. Young adults average about 170 mg of cholesterol per 100 mL of blood, whereas males at age 55 may have cholesterol levels at 250 mg/100 mL or higher because the rate of cholesterol breakdown decreases with age. Females tend to have lower blood cholesterol levels than males.
To understand the link between heart disease and cholesterol levels, it is important to understand how cholesterol and other lipids are transported in the body. Lipids, such as cholesterol, are not soluble in water and therefore cannot be transported in the blood (an aqueous medium) unless they are complexed with proteins that are soluble in water, forming assemblages called lipoproteins . Lipoproteins are classified according to their density, which is dependent on the relative amounts of protein and lipid they contain. Lipids are less dense than proteins, so lipoproteins containing a greater proportion of lipid are less dense than those containing a greater proportion of protein.
Research on cholesterol and its role in heart disease has focused on serum levels of low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs). One of the most fascinating discoveries is that high levels of HDLs reduce a person’s risk of developing heart disease, whereas high levels of LDLs increase that risk. Thus the serum LDL:HDL ratio is a better predictor of heart disease risk than the overall level of serum cholesterol. Persons who, because of hereditary or dietary factors, have high LDL:HDL ratios in their blood have a higher incidence of heart disease.
How do HDLs reduce the risk of developing heart disease? No one knows for sure, but one role of HDLs appears to be the transport of excess cholesterol to the liver, where it can be metabolized. Therefore, HDLs aid in removing cholesterol from blood and from the smooth muscle cells of the arterial wall.
LDL's transport cholesterol from the liver to the cells where they are incorporated into membrane or transformed to other steroids. Therfore high LDL levels are warning signs of atherosclerosis, the build up of cholesterol containing deposits in the arteries.
Dietary modifications and increased physical activity can help lower total cholesterol and improve the LDL:HDL ratio. The average American consumes about 600 mg of cholesterol from animal products each day and also synthesizes approximately 1 g of cholesterol each day, mostly in the liver. The amount of cholesterol synthesized is controlled by the cholesterol level in the blood; when the blood cholesterol level exceeds 150 mg/100 mL, the rate of cholesterol biosynthesis is halved. Hence, if cholesterol is present in the diet, a feedback mechanism suppresses its synthesis in the liver. However, the ratio of suppression is not a 1:1 ratio; the reduction in biosynthesis does not equal the amount of cholesterol ingested. Thus, dietary substitutions of unsaturated fat for saturated fat, as well as a reduction in consumption of trans fatty acids, is recommended to help lower serum cholesterol and the risk of heart disease.
Steroid Hormones
Hormones are chemical messengers that are released in one tissue and transported through the circulatory system to one or more other tissues. They are molecules that regulate the function of organs and tissues. One group of hormones is known as steroid hormones because these hormones are synthesized from cholesterol, which is also a steroid. There are two main groups of steroid hormones: adrenocortical hormones and sex hormones.
Adrenocorticoid Hormones
The adrenocortical hormones, such as cortisone and cortisol are produced by the adrenal gland, which is located adjacent to each kidney. They are produced from cholesterol through progesterone. These compounds are anti-inflammatory agents. Cortisol and its analogs are therefore used pharmacologically as immunosuppressants after transplant operations and in the treatment of severe skin allergies and autoimmune diseases, such as rheumatoid arthritis.
Figure \(\PageIndex{3}\) Manufacture of cortisol and cortisone starts from cholesterol.
Sex Hormones
The sex hormones are a class of steroid hormones secreted by the gonads (ovaries or testes), the placenta, and the adrenal glands. They are produced from cholesterol by the shortening of the hydrocarbon chain and alterations to the ring producing progesterone. Progesterone is then converted through several steps to testosterone and estradiol.Testosterone is a male sex hormones, controlling the primary sexual characteristics of males. Two kinds of sex hormones are of particular importance in females: progesterone, which prepares the uterus for pregnancy and prevents the further release of eggs from the ovaries during pregnancy, and the estradiol, which are mainly responsible for the development of female secondary sexual characteristics. Both males and females produce these hormones, differing in the amounts of secreted hormones rather than in the presence or absence of one or the other. Cholesterol is the starting material for the production of these hormones.
Figure \(\PageIndex{4}\) Cholesterol is the starting material for the synthesis of the sex hormpnes.
| Hormone | Effect |
|---|---|
| regulates salt metabolism; stimulates kidneys to retain sodium and excrete potassium | |
| stimulates the conversion of proteins to carbohydrates | |
| regulates the menstrual cycle; maintains pregnancy | |
| stimulates female sex characteristics; regulates changes during the menstrual cycle | |
| stimulates and maintains male sex characteristics |
Sex hormones, both natural and synthetic, are sometimes used therapeutically. For example, a woman who has had her ovaries removed may be given female hormones to compensate. Some of the earliest chemical compounds employed in cancer chemotherapy were sex hormones. For example, estrogens are one treatment option for prostate cancer because they block the release and activity of testosterone. Testosterone enhances prostate cancer growth. Sex hormones are also administered in preparation for sex-change operations, to promote the development of the proper secondary sexual characteristics. Oral contraceptives are synthetic derivatives of the female sex hormones; they work by preventing ovulation.
Bile Salts
Bile is a yellowish green liquid (pH 7.8–8.6) produced in the liver. The most important constituents of bile are bile salts, which are sodium salts of glycocholate and taurocholate. They are synthesized from cholesterol in the liver, stored in the gallbladder, and then secreted in bile into the small intestine.
Because they contain both hydrophobic and hydrophilic groups, bile salts are amphipathic and highly effective emulsifying agents; they break down large fat globules into smaller ones and keep those smaller globules suspended in the aqueous digestive environment. Enzymes can then hydrolyze fat molecules more efficiently. Thus, the major function of bile salts is to aid in the digestion of dietary lipids.
Surgical removal is often advised for a gallbladder that becomes infected, inflamed, or perforated. This surgery does not seriously affect digestion because bile is still produced by the liver, but the liver’s bile is more dilute and its secretion into the small intestine is not as closely tied to the arrival of food.
Summary
Steroids have a four-fused-ring structure and have a variety of functions. Cholesterol is a steroid found in mammals that is needed for the rigidity of cell membranes, synthesis of bile acids, and several hormones. Bile salts are secreted into the small intestine to aid in the digestion of fats.