What are steroid hormones?

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Steroid hormones—hormones containing a steroid ring derived from cholesterol—are important for many processes that control sex determination, reproduction, behavior, and metabolism. Mutations in the genes that produce or regulate the action of specific steroid hormones may lead to infertility, sterility, sex determination, osteoporosis, autoimmune diseases, heart abnormalities, and breast, uterine, and prostate cancer.
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Steroid Hormone Characteristics and Function

Steroid hormones represent a group of hormones that all contain a characteristic “steroid” ring structure. This steroid ring is derived from cholesterol, and cholesterol is the starting material for the production of different steroid hormones. Steroid hormones, like other types of hormones, are secreted by endocrine glands into the bloodstream and travel throughout the body before having an effect. All steroid hormones, although specific for the regulation of certain genes, function in a similar manner. Because steroid hormones are derived from cholesterol, they have the unique ability to diffuse through a cell’s outer plasma membrane. Inside the cell, the steroid hormone binds to its specific receptor in the cytoplasm. Upon binding, the newly formed hormone-receptor complex relocates to the nucleus. In the nucleus, the hormone-receptor complex binds to the DNA in the promoter region of certain genes at specific nucleotide sequences termed hormone-responsive elements. The binding of the hormone-receptor complex to hormone-responsive elements causes the increased production of transcription and protein production in most cases. In some instances, binding to a specific hormone-responsive element will stop the production of proteins that are usually made in the absence of the hormone.

There are two types (sex steroid and adrenal steroid) and five classes of steroid hormones. The sex steroid hormones include the androgens, estrogens, and progestins and are produced by the male testes (androgens) and female ovaries. Adrenal steroid hormones include glucocorticoids and mineralocorticoids and are produced by the adrenal glands.

Sex Steroid Hormones

Sex steroid hormone genes are responsible for determining the sex and development of males and females. Androgens are a group of steroid hormones that cause masculinization. The principal androgen is testosterone, which is produced by the testes and is responsible for male secondary sexual characteristics (growth of facial and pubic hair, deepening of voice, sperm production). Estrogens are sex steroid hormones produced in the ovaries and cause femininization. In addition, estrogens control calcium content in the bones, modulate other hormones produced in the ovary, modify sexual behavior, regulate secondary sex characteristics (menstrual periods, breast development, growth of pubic hair), and are essential for pregnancy to occur. The most potent estrogen is 17-beta estradiol. Progestins, including progesterone, are also sex steroid hormones. Progesterone is important for proper breast development and normal and healthy pregnancies; it functions in the mother to alter endometrial cells so the embryo can implant. The loss of progesterone at the end of a pregnancy aids in the beginning of uterine contractions.

Anabolic steroids are drugs derived from the male steroid hormone testosterone and were developed in the late 1930s to treat hypogonadism in men, a condition that results in insufficient testosterone production by the testes. During this same period, scientists discovered that anabolic steroids also increased the muscle mass in animals. These findings led to the use of anabolic steroids by bodybuilders, weightlifters, and other athletes to increase muscle mass and enhance performance. Anabolic steroid use can seriously affect the long-term health of an individual and in women results in masculinization.

Adrenal Steroid Hormones

Adrenal steroid hormones are secreted from the adrenal cortex and are important for many bodily functions, including response to stress and maintenance of blood sugar levels, fluid balance, and electrolytes. The glucocorticoids represent one class of adrenal steroid hormone. The most important, cortisol, performs critically important functions; it helps to maintain blood pressure and can decrease the response of the body’s immune system. Cortisol can also elevate blood sugar levels and helps to control the amount of water in the body. Elevated cortisol helps the body respond to stress. The glucocorticoids cortisone and hydrocortisone are used as anti-inflammatory drugs to control itching, swelling, pain, and other inflammatory reactions. Prednisone and prednisolone, also members of the glucocorticoid class of hormones, are the broadest anti-inflammatory and immunosuppressive medications available.

The second class of adrenal steroid hormones is the mineralocorticoids, including aldosterone, which helps maintain salt and water balance and increases blood pressure. Aldosterone is crucial for retaining sodium in the kidney, salivary glands, sweat glands, and colon.

Genetic Defects Affecting Sex Steroid Hormones

Defects in the genes involved in the production of sex steroid hormones can have serious consequences. Mutations in the androgen receptor, the receptor for testosterone, result in androgen insensitivity syndrome. In this syndrome, the individual has the genes of a male (XY) but develops, behaves, and appears female. Other gene defects in androgen biosynthesis often result in sterility. Genetic defects in estrogen receptors or estradiol biosynthesis lead to infertility. Reduced levels of estradiol have also been linked to bone loss (osteoporosis) and infertility, whereas excessive levels are associated with an increased risk of breast and uterine cancer. Similarly, genetic mutations in the progesterone production pathway or the progesterone receptor are associated with infertility. In addition, bone loss is one of the most serious results of progesterone deficiency, made worse by inappropriate diet and lack of exercise.

Genetic Defects Affecting Adrenal Steroid Hormones

Genetic abnormalities in adrenal steroid hormone biosynthesis are known to cause hypertension in some cases of congenital adrenal hyperplasia (CAH). In people with this condition, hypertension usually accompanies a characteristic phenotype with abnormal sexual differentiation. CAH is a family of autosomal recessive disorders of adrenal steroidogenesis. Each disorder has a specific pattern of hormonal abnormalities resulting from a deficiency of one of the enzymes necessary for cortisol synthesis. The most common form of CAH is 21-hydroxylase deficiency; however, in all forms, cortisol production is impaired, which results in an increase in adrenocorticotropin and the overproduction of androgen steroids.

There are two major forms of 21-hydroxylase deficiency. Classic CAH deficiency results in masculinized girls who are born with genital ambiguity and may possess both female and male genitalia. Nonclassic 21-hydroxylase deficiency does not produce ambiguous genitalia in female infants but may result in premature puberty, short stature, menstrual irregularities or lack of a menstrual cycle, and infertility. Familial glucocorticoid deficiency (FGD) is an extremely rare, genetic autosomal recessive condition in which a part of the adrenal glands is destroyed. These changes result in very low levels of cortisol. Although this disease is easily treatable if recognized, when left untreated it is often fatal or can lead to severe mental disability.

The genetic basis of four forms of severe hypertension transmitted on an autosomal basis has also been determined. All of these conditions are characterized by salt-sensitive increases in blood pressure, indicating an increased mineralocorticoid effect. The four disorders—aldosteronism, mineralocorticoid excess syndrome, activating mutation of the mineralocorticoid receptor, and Liddle syndrome—are a consequence of either abnormal biosynthesis, abnormal metabolism, or abnormal action of steroid hormones and the development of hypertension. Adrenal insufficiency is known as Addison’s disease and causes death within two weeks unless treated. Classical Addison’s disease results from a loss of both cortisol and aldosterone secretion as a result of the near total or total destruction of both adrenal glands.

Key terms anabolic steroids : drugs derived from androgens and used to enhance performance in sports androgens : steroid hormones that cause masculinization estrogens : steroid hormones that produce female characteristics glucocorticoids : steroid hormones that respond to stress and maintain sugar, salt, and body fluid levels hormones : chemical messengers produced by endocrine glands and secreted into the blood mineralocorticoids : a group of steroid hormones important for maintenance of salt and water balance progestins : steroid hormones important for pregnancy and breast development testosterone : the principal androgen, produced by the testes and responsible for male secondary sexual characteristics Bibliography

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