Steroid compounds are powerful drug substances generally well known in biology, medicine and pharmaceutical sciences. These compounds effect a number of important physiological functions in mammals and in human beings in particular. Steroid hormones are secreted by the adrenal cortex, testis, ovary and placenta and include the androgens (such as testosterone), estrogens (such as estradiol and estrone), glucocorticoids (cortisone, corticosterone, and cortisol), mineralocorticoids (primarily aldosterone), and progestogens (primarily progesterone). Steroid hormones regulate proliferation and differentiation in target cells within the reproductive tract, mammary gland, and peripheral tissues such as the bones, heart, blood vessels, and hair follicles. The androgen class of steroidal hormones is responsible for the difference in the physical characteristics of males and females. The androgen receptor is a ligand-activated transcriptional regulatory protein that mediates induction of male sexual development and function through its activity with endogenous androgens.
Androgens are generally known as the male sex hormones. The androgenic hormones are steroids which are produced in the body by the testes and the cortex of the adrenal gland or can be synthesizedy. Androgenic steroids play an important role in many physiologic processes, including the development and maintenance of male sexual characteristics such as muscle and bone mass, prostate growth, spermatogenesis, and the male hair pattern. Over-production of these hormones in the body results in many undesirable physical manifestations and disease states, e.g. acne vulgaris, alopecia, seborrhoea, female hirsutism, benign prostatic hypertrophy and male pattern baldness. Steroid hormones, such as the estrogens and the androgens, represent an important class of clinically administered compounds. Estrogens are used extensively for replacement therapy, treatment of hypogonadism, and contraception. The androgens, and particularly testosterone, are used in replacement therapy, treatment of gynecologic disorders, as protein anabolic agents, and as metabolic stimulators.
Androgen decline in the aging male (ADAM) refers to a progressive decrease in androgen production, common in males after middle age. Clinical manifestations include fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, obesity, sarcopenia, osteopenia, benign prostate hyperplasia, and alterations in mood and cognition. Androgen deficiency in female (ADIF) refers to a variety of hormone-related conditions including, common in females after middle agest. The syndrome is characterized by sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, anemia, depression, anemia, hair loss, obesity, endometriosis, breast cancer, uterine cancer and ovarian cancer. The endogenous steroidal androgens include testosterone and dihydrotestosterone (DHT). Testosterone is the principal steroid secreted by the testes and is the primary circulating androgen found in the plasma of males. Testosterone is the prohormone of 5-alpha-dihydrotestosterone which is formed locally in the above organs by the action of testosterone 5-alpha-reductase. Testosterone is converted to DHT by the enzyme 5 alpha-reductase in many peripheral tissues. DHT is thus thought to serve as the intracellular mediator for most androgen actions. Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-Methyl-Nortestosterone (MENT) and its acetate ester. Testosterone enanthate is the most widely used of these esters. Administration of the male sex steroids (e.g., testosterone and its derivatives) has shown particular promise in this regard due to the combined gonadotropin-suppressing and androgen-substituting properties of these compounds. Hydroxy steroids such as oestradiol and testosterone have been investigated for use in the treatment of osteoporosis, either by inhibition of bone resorption or stimulation of bone formation, and bisphosphonates such as disodium etidronate and clodronate are also known as bone resorption inhibitors.
Progesterone is a steroid hormone that is produced by the ovaries during a woman's child-bearing years. Progesterone is also made, although in smaller amounts, by the adrenal glands in both sexes and by the testes in males. Progesterone released during the luteal phase of the normal female cycle leads to development of a secretary endometrium. Progesterone influences the endocervical glands, and progesterone is very important for the maintenance of pregnancy as progesterone suppresses menstruation and uterine contractility. Progesterone plays a major role in reproductive health and functioning. Progesterone has been found to be a major precursor in the biosynthesis of most other steroids, particularly glucocorticoids, androgens and estrogens. Progesterone also stimulates the growth of the uterus and a number of specific changes in the endometrium and myometrium. Progesterone is essential for the development of decidual tissue and the differentiation of luminal and glandular epithelial tissue. Progesterone also plays several roles in gestation, including breast enlargement, inhibition of uterine contractility, maintenance of gestation, immunological protection of the embryo, and inhibition of prostaglandin synthesis. Progesterone, which surges following ovulation, maintains the secretory endometrium and thus, helps to ensure the survival of the embryo and fetus. It also acts as a diuretic, an antidepressant, and as a precursor of corticosteroids and of other sex hormones, notably estrogen and testosterone. There is also evidence that progesterone affords protection against loss of libido, osteoporosis, endometrial cancer, breast cancer, and fibrotic cysts.
Medroxyprogesterone (MAH), also known as 6.alpha.-methyl-17-hydroxyprogesterone, is a synthetic progestin with a pharmacological activity about 15 times greater than progesterone. Mifepristone, also known as RU-486, is an antiprogesterone drug that blocks receptors of progesterone. It counteracts the effects of progesterone, which is needed to sustain pregnancy. Mifepristone induces spontaneous abortion when administered in early pregnancy followed by treatment with the prostaglandin, misoprostol. Danazol is a synthetic steroid derived from ethinyl testosterone. Danazol indirectly reduces estrogen production by lowering pituitary synthesis of follicle-stimulating hormone and LH. Danazol also binds to sex hormone receptors in target tissues, producing anabolic, antiestrogenic, and weakly androgenic activity. Corticosteroids are used to relieve inflammation and to suppress the immune response. They inhibit eosinophil, basophil, and airway epithelial cell function by regulation of cytokines that mediate the inflammatory response. They inhibit leukocyte infiltration at the site of inflammation, interfere in the function of mediators of the inflammatory response, and suppress the humoral immune response. Corticosteroids are used to treat allergies, asthma, arthritis, and skin conditions. |
|
