Steroid hormones corticosteroids

Steroid hormones can be subdivided into sex hormones (androgens, estrogens, and progestins) and corticosteroids (glucocorticoids and mineralocorticoids). 

Ligand-bound corticosteroid receptors have been shown to interact to form heterodimers with other transcription factors, such as the jun protein. Such interactions are responsible for transactivation of the ds-regulatory sites known as AP-1 sites and for the glucocorticoid-mediated suppression of transcription, such as that seen in the pro-opiomelanocortin gene. A number of such specific protein interactions have been reported these interactions and their locations relative to other transcription factors transform a ubiquitous steroid hormone signal into a tissue-specific, graded cellular response. 

Steroid hormones Estrogens Androgens Gestagens Corticosteroids... 

The interaction between the adrenal cortex of the foetus and the placenta in production of steroid hormones is complex. In outline, the placenta produces progesterone from cholesterol (which is available from the maternal blood) whereas the foetal adrenal cortex produces corticosteroids and androgens from the progesterone produced in the placenta. The placenta then converts some of these androgens into oestrogens. The interplay between the placenta and the foetal adrenal cortex is acknowledged by the use of the term foeto-placental unit to describe steroido-... 

The tenn corticosteroids refers to steroid hormones secreted by the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Cortisone is a natural corticosteroid secreted by the adrenal cortex along with many steroidal hormones. It has mainly glucocorticoidal activity and some degree of mineralo-corticoid activity. 

The steroid hormones are distributed throughout the entire organism by means of the circulatory system. Transport often occurs in the form of a complex with a specific binding protein. An example for such a binding protein is transcortin, which is responsible for the transport of the corticosteroids. The steroid hormones enter the cell by diffusion and activate the cytosolic receptors. 

Steroid hormones are secreted on demand from their tissues of origin in response to hormonal signals. The corticosteroids and androgens are made in different regions of the adrenal cortex, and are secreted into blood in response to different signals. 

Corticosteroids have been useful in the treatment of acute leukemia, lymphoma, multiple myeloma, and other hematologic malignancies as well as in advanced breast cancer. In addition, they are effective as supportive therapy in the management of cancer-related hypercalcemia. The steroid hormones and related agents most useful in cancer therapy are listed in Table 55-5. 

The mechanisms of action of steroid hormones on lymphoid, mammary, and prostatic cancer have been partially clarified. Specific cell surface receptors have been identified for estrogen, progesterone, corticosteroids, and androgens in neoplastic cells in these tissues. As in normal cells, steroid hormones also form an intracellular steroid-receptor complex that ultimately binds directly to nuclear proteins associated with DNA to activate transcription of a broad range of cellular genes involved in cell growth and proliferation (see Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists). 

There are many types of steroid hormones in the body, such as the sex/gonadal hormones testosterone and estrogen, thyroid hormones, growth hormones, and stress hormones, which serve various normal functions. One type of steroid— corticosteroids or glucocorticoids—is secreted by the adrenal glands (located just above the kidneys). These steroids, particularly synthetic versions of them, have powerful antiinflammatory actions that help to relieve pain. They are often given as an epidural injection to relieve neck or back pain that results from a compressed or pinched nerve. They can also be injected directly into a joint to relieve pain caused by inflammation in conditions such as tendonitis (inflammation of the tendons), carpal tunnel syndrome, tennis elbow, bursitis (inflammation of sac-like cavities in tendons or muscles that allow them to slide easily over bone), or other joint pain. Professional athletes, who routinely experience one or more of these conditions, are often given local steroid injections. Frequently, the steroid is combined with a local anesthetic such as lidocaine. 

During the past 50 years, numerous experiments have been performed in attempts to unravel the complex pathways whereby steroid hormones, that is the corticosteroids, androgens and oestrogens, are formed in mammalian and other tissues. A very large number of books and reviews have already been written on the subject and this present chapter will seek to (a) summarize the pathways concerned and how the evidence for these was obtained and (b) provide an update of advances over the past decade, particularly with regard to the properties of the steroid transforming enzymes involved and the mechanism of the reactions catalysed by such enzymes. 

Betamethasone is a corticosteroid. Corticosteroids are very lipophilic (due to their hydrocarbon skeleton) and as a result can passively diffuse into target cells. It acts by binding to the intracellular corticosteroid receptor protein, which is found within the cytosol. The resulting complex translocates to the nucleus and induces synthesis of mediator proteins (e.g. metabolic enzymes and lipocortin). The binding of steroid hormones to their receptors causes changes in gene transcription and cell function. Corticosteroids reduce the inflammatory reaction by limiting capillary dilatation and vascular permeability. 

Taylor et al. [39,56] analyzed a mixture of corticosteroids in extracts of equine urine and plasma. Gradient elution was used to facilitate trace enrichment at the head of the column. Huber et al. [36] presented another illustration for the use of capillary electrochromatography with gradient elution. Five steroid hormones were separated by using a capillary column packed with 6-pm Zorbax ODS stationary phase. 

If as above we simply represent alicyclic rings sharing two Gs by a vertical line, then we can represent the basic tetracyclic structure of lanosterol as G61G61 G6 C5 (noting that there are two double bonds and various alkyl substituents and also a 3-hydroxyl on the first of the alicyclic rings). Many subsequent reactions yield cholesterol, a major triterpene membrane component that modifies the fluidity of animal cell membranes and is a precursor for synthesis of animal bile acids (fat solubilizing amphipathic detergents) plant triterpenes and steroid hormones such as the corticosteroids cortisol and cortisone, the mineralocorticoid aldosterone and the sex hormones testosterone and 17-(3-oestradiol. The structure and bioactivity of the plant terpenes is sketched below. 

The steroid hormones are hydrophobic, this property enabling them to readily cross the plasma membrane to bind their respective cytosolic receptors. However, transport of such hydrophobic hormones through the blood stream requires hormone-binding proteins such as the steroid-binding globulins and corticosteroid-binding globulins. 

Steroids A large family of drugs related to the adrenal hormone cortisone. They include anabolic steroids and corticosteroids. 

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