Explain The Mode Of Action Of Steroid Hormones

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    Mechanism of Action of Steroid Hormones: Animation

    explain the mode of action of steroid hormones Steroid hormones are produced in the adrenal glands, ovaries, and testes, and regulate a wide range of physiologic functions. This review covers the action of sex steroids, with emphasis on the estrogens and progestins. A review of the action of sex steroid hormones, actipn natural and synthetic, should begin with or description of endogenous sources and a definition explain the mode of action of steroid hormones such substances. Estrogens display one common biologic activity, the ability to stimulate growth and maintain testosterone amplifier methyl andro female sex characteristics. As mediators of growth and differentiation of the reproductive tract in the nonpregnant woman, estrogens are produced predominantly by the ovary and in a clearly defined pattern that is related to changes in both explaun and morphology attuned to the menstrual cycle. Estrogens are the most important steroids produced by the developing ovarian follicle.

    Mechanism of Action of Steroid Hormones: Animation ~ MedchromeTube - Best Medical Videos

    explain the mode of action of steroid hormones

    Steroid hormones are produced in the adrenal glands, ovaries, and testes, and regulate a wide range of physiologic functions. This review covers the action of sex steroids, with emphasis on the estrogens and progestins.

    A review of the action of sex steroid hormones, both natural and synthetic, should begin with a description of endogenous sources and a definition of such substances. Estrogens display one common biologic activity, the ability to stimulate growth and maintain the female sex characteristics.

    As mediators of growth and differentiation of the reproductive tract in the nonpregnant woman, estrogens are produced predominantly by the ovary and in a clearly defined pattern that is related to changes in both physiology and morphology attuned to the menstrual cycle. Estrogens are the most important steroids produced by the developing ovarian follicle.

    As the follicle reaches preovulatory size, estrogen synthesis reaches a maximum. Serum levels increase dramatically before ovulation, and are responsible for the positive feedback signal that triggers the release of luteinizing hormone LH from the pituitary gland, which in turn induces ovulation. In the second half of the menstrual cycle, after ovulation, estrogen is produced by the corpus luteum, although to a lesser degree and of secondary importance compared with progesterone production.

    In the first half of the cycle, estrogens are responsible for the growth of the uterine endometrium proliferative phase ; in the second half, progesterone action results in the secretory endometrium characteristic of the luteal phase of the menstrual cycle. For these reasons, estriol is almost exclusively an estrogen of pregnancy. The actions of estrogen are not limited to the reproductive tract and to purely endocrine interrelationships; there are many systemic effects beyond the scope of this review.

    Progestogens, as indicated by the name, are hormones whose major function is the maintenance of pregnancy. They have been specifically defined as agents that induce secretory changes in the proliferative endometrium and maintain pregnancy after ovariectomy in laboratory rodents. This hormone does not display the multiplicity of systemic effects characteristic of the estrogens; its action is limited predominantly to the reproductive organs. The elevation of the basal body temperature after ovulation is due to the thermogenic effect of progesterone at the level of the hypothalamus.

    Progesterone is produced by all tissues that have steroidogenic activity, and is a major component in the pathway of synthesis of many steroid hormones; therefore, low levels of progesterone are always produced by steroidogenic tissues.

    The weak progestogen hydroxy progesterone also is produced by the ovary in a predictable pattern in relation to follicular and luteal function. The placenta assumes the function of progesterone production between the fifth and seventh weeks of gestation, and it produces increasing amounts during the course of pregnancy. The maintenance of pregnancy is dependent on the continued production of progesterone, first from the corpus luteum and, after a gradual shift, from the placenta for the remainder of pregnancy.

    Endogenous and exogenous steroid hormones are transported through the circulatory system to the target organs where they exert their specific hormonal actions.

    Steroids bind to a variety of macromolecules in the circulation. The measurement of serum or plasma steroid concentration generally is a measure of the total steroid present and does not reflect the equilibrium that exists between steroid hormone bound to these macromolecules and those free in the blood.

    The bound and free forms of the steroid are in an equilibrium that is controlled by many physiologic factors. It is important to remember that generally only the free hormone can leave the circulation and enter the target cells, where it can bind to specific intracellular receptors to initiate the biochemical expression of specific sex steroids.

    Its production is stimulated by increasing estrogen concentration and decreased by increasing testosterone concentration. The plasma concentration of this binding globulin is increased by estrogen; consequently, it is increased dramatically during pregnancy. In addition to the binding of steroids by these high-affinity, low-capacity macromolecules, albumin is a sex steroid binder with low affinity but tremendous capacity in the circulation.

    At such a high concentration, it can alter the equilibrium distribution of steroids in blood, and therefore is an important consideration in the circulating economy of steroid hormones. Because of the greater concentration of albumin and the rapid dissociation of steroids from this low-affinity binder, albumin may serve a more important regulatory role than do the high-affinity, low-capacity binding proteins.

    Steroid hormones in the circulation e. The free hormones cross cell membranes in all tissues in the body, but only those tissues that are specific targets for steroids have receptors that bind and retain the steroids, leading to an intracellular accumulation that eventually allows the biologic expression that is characteristic of the particular steroid.

    These receptors are markedly different from gonadotropin receptors, which are localized in the cell membrane and have several second-messenger systems as mediators of receptor binding. Steroid receptors were identified many years ago, when radioactively labeled steroids became available. The dogma that persisted for many years was of the presence of an unoccupied cytoplasmic receptor that would bind the steroids that crossed the cell membrane into the cytoplasm.

    After binding, this unit was activated, and it crossed the nuclear membrane to bind within the nucleus and cause the expression of specific genes related to specific steroid actions.

    In the last few years, several studies changed the interpretation of this process. In particular, the availability of specific antibodies against the estrogen receptor showed that these steroid hormone receptors, occupied or unoccupied, are localized primarily in the nucleus.

    Earlier studies required tissue homogenization and centrifugation to separate the cytosolic and nuclear fractions. Because the unoccupied receptor in the nucleus is not tightly bound to nuclear proteins, it was easily translocated into the cytosolic fraction.

    On the other hand, the occupied receptor is specifically bound to structural components in the nucleus and, consequently, remained localized in that fraction. Therefore, the early suggestion of an unoccupied cytosolic receptor and an occupied nuclear receptor were artifacts of the homogenization and separation procedure. The availability of specific antibodies for estrogen receptors and their use in immunochemistry has allowed visualization of both free and occupied receptors in the nucleus.

    Although these studies were done initially with the estrogen receptor, other steroid-receptor interactions also have been investigated, with similar results. In addition, other methods that have allowed the separation of cytoplasmic and nuclear fractions before the trauma of homogenization and centrifugation have confirmed these localizations. The retention of the steroid-receptor complex in the nucleus is an important function in the mechanism by which steroids exert their biochemical actions.

    For example, estrogenic compounds that do not cause nuclear accumulation for 6 hours or longer e. Thus, not only production of RNA but also retention time in the nucleus is necessary for true expression of steroid activity. The intranuclear steroid-receptor complex binds to the target cell genome as the next step in the sequence of events in the expression of steroid activity.

    The binding of the steroid-receptor complex to chromatin of the target cell is highly specific. Little binding occurs to nontarget chromatin or with free hormone alone. This association initiates the production of specific messenger ribonucleic acids in the target cell. This evidence suggests that steroid hormones regulate gene expression primarily at a transcriptional level.

    These mRNAs are then exported to the cytoplasm, where protein synthesis takes place, resulting in alterations in cell growth or physiology that are characteristic of the steroid hormone for that target issue. The concentration of steroid receptors in target cells is not constant, but varies with the stage of the menstrual cycle or, more importantly, with the recent history of hormonal exposure. Animal studies show that the concentration of sex steroid receptors changes after castration; the mechanism of regulation of receptor content is not the same for each steroid receptor.

    For example, estrogen treatment not only stimulates the production of estrogen receptors, but also results in the production of new progesterone receptors. Conversely, progesterone treatment results in a decrease in both progestin and estrogen cytoplasmic receptors.

    The concentration of steroid receptors in target tissues is not constant, and these receptors must be present for tissues to respond to specific sex hormone treatment. Therefore, the response to any administered sex steroid may vary with the stage of the menstrual cycle and its varying steroidal milieu or with the duration and nature of any previous exposure to steroid treatment.

    Knowledge of tissue receptor concentrations may serve a valuable diagnostic function. Perhaps the most important example of the use of estrogen E r and progesterone receptor P r concentration is in breast tumor biopsy specimens taken to determine the potential value of endocrine versus nonendocrine therapy. It was known for many years that some patients with breast cancer would respond to endocrine ablative therapy, whereas others would not.

    With the knowledge and techniques for E r and P r measurement in small tumor biopsy specimens, a positive correlation was found between tumors with positive steroid receptor content and application of endocrine treatments. It is interesting that the emerging predominant treatment for these E r tumors is tamoxifen, a specific estrogen antagonist that competes with natural estrogens for the receptors in these tumors, thereby obviating the necessity of removing the gonads or adrenals.

    Estrogens The natural estrogens estradiol, estrone, and estriol were isolated in the late s and s. Originally, it was thought that these steroids were orally inactive. The first orally active estrogen was the nonsteroidal compound diethylstilbestrol. The first orally active steroidal estrogen, ethynyl estradiol, was developed in by attaching an ethynyl group at C of the estradiol molecule.

    These two compounds remain the only orally active synthetic estrogens used in birth control formulations today. Mestranol may be less potent under certain circumstances than ethinyl estradiol because mestranol first must be converted to ethinyl estradiol to be active. Mestranol will not bind to the cytoplasmic estrogen receptor; therefore, ethinyl estradiol is the active estrogen for both of these synthetic compounds.

    Progestogens The discovery that ethinyl substitution leads to oral potency led to the preparation of ethisterone, an orally active derivative of testosterone. In , it was found that removal of the carbon from ethisterone to form norethindrone did not destroy the oral activity and, most importantly, changed the major hormonal effect from that of an androgen to that of a progestogen. Accordingly, the progestational derivatives of testosterone were designated nortestosterones.

    The androgenic properties of these compounds, however, were not completely eliminated, and minimal anabolic and androgenic activity remains. Examples of this class of progestogens include norethindrone, norethynodrel, ethynodiol diacetate, and some other related compounds not used in the United States.

    The second group of nor compounds are gonanes, which have an ethyl instead of an methyl group. They include racemic norgestrel, levonorgestrel, and three newer compounds: A second group of progestogens became available for use when it was discovered that acetylation of the hydroxy group of hydroxyprogesterone produced oral potency. Acetylation of the 17 position gives oral potency, but an addition at the 6 position is necessary to give sufficient progestional strength for human use, probably by inhibiting degradative metabolism.

    The chief examples of this class are medroxyprogesterone acetate MPA , megestrol acetate, and chlormadinone acetate CMA. These compounds, with the exception of depot medroxyprogesterone acetate and progestogen-only minipills, are used clinically in combination with an ethynyl estrogen. Therefore, it is inappropriate to extrapolate the various biologic activities of the progestogens as determined in animal assays of the pure compound to a clinical situation where a particular ratio of estrogen to progestogen has been chosen to maximize contraceptive efficacy and endometrial control.

    The natural sex steroids exert their influence at all levels of reproductive function, including the hypothalamic-pituitary-gonadal endocrine axis as well as the physiologic regulation of the reproductive system, so it is not surprising that the synthetic estrogens and progestogens can exert some regulatory function at many sites in the body. The following sections discuss some of these modes of action.

    Nervous System, Hypothalamus, and Pituitary Sex hormones affect the central nervous system in regions other than the hypothalamopituitary system. For example, the amygdala and cerebellum participate in the feedback effects of progesterone. EEG evidence points toward a mode of action similar to that of the minor tranquilizers. Large intravenous doses have an anesthetic effect in humans. The relationship of the corpus luteum hormone to infertility and inhibition of ovulation was under investigation in the early part of this century.

    By , the biphasic effect of progesterone on ovulation in the rat had been recognized. Lesions in the suprachiasmatic region block the progesterone-stimulated release of LH but not that of follicle-stimulating hormone.

    This finding appears to indicate that progesterone, and probably other progestational compounds as well, can exert qualitative as well as quantitative influences on gonadotropin release. The prevailing level of estrogen is important in the response of the hypothalamopituitary system to progestogens, 26 which may explain why intracerebral implants of progesterone can induce or inhibit ovulation in rats, depending on the time of the cycle at which the experiment is performed.

    Experiments attempting to localize the action of hormones to the hypothalamus versus the anterior pituitary are complicated by blood flow through the portal system from the median eminence to the pituitary on the one hand and by technical difficulties causing drugs to travel in the reverse direction on the other. Experiments in immature female rats given radioactive progesterone showed little retention of radioactivity in the hypothalamus, but selective and prolonged pituitary uptake.

    Clinical observations of the effect of continuous administration of synthetic progestational compounds agree with the findings in laboratory animals. Depending on the potency and dose of the administered progestogen, the first inhibitory effect to be observed is a diminution 32 or suppression of the midcycle LH surge.

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