Steroid Hormones Introduction

Minor changes in the stereochemistry and substitution pattern of the steran skeleton result in vastly different yet specific physiological and pharmacological effects, which in turn influence developmental, metabolic, and behavioral phenomena. The organic chemistry and biochemistry of steroids is the subject of many excellent books and an enormous amount of research and patent literature. This chapter compares and contrasts the structure and mode of action of various steroids, their role in regulating hormonal secretion, and the timing of this regulatory action. 

One of the most unique and powerful features of steroid hormones is the nature of the steroid receptor. Unlike most other hormones or drugs, which target protein receptors usually embedded in membranes, steroids target the genes themselves, buried deep within the nucleus of the cell. 

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We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

The introduction of the sulfa drugs was followed by the development of the penicillin antibiotics. Fleming s chance observation of the anti-bacterial action of the penicillin mold in 1928 and the subsequent isolation and identification of its active constituent by Florey and Chain in 1940 marked the beginning of the antibiotics era that still continues today. At roughly the same time, the steroid hormones found their way into medical practice. Cortisone was introduced by the pharmaceutical industry in 1944 as a drug for the treatment of arthritis and rheumatic fever. This was followed by the development of steroid hormones as the active constituents of the contraceptive pill. 

The steroid hormones (glucocorticoids, mineralocorticoids, and sex hormones) are produced from cholesterol by alteration of the side chain and introduction of oxygen atoms into the steroid ring system. In addition to cholesterol, a wide variety of isoprenoid compounds are derived from mevalonate through condensations of isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

Steroid hormones are generally converted into inactive metaboic excretion products in the liver. Reactions include reduction of unsaturated bonds and the introduction of additional hydroxyl groups. The) resulting structures are made more soluble by conjugation with curonic acid or sulfate (from PAPS, see p. 160). Approximate ) twenty to thirty percent of these metabolites are secreted into the bile and then excreted in the feces, whereas the remainder ae t released into the blood and filtered from the plasma in the kidney, passing into the urine. These conjugated metabolites are fairb1 water-soluble and do not need protein carriers. 

The minor revolution in our knowledge about molecular aspects of steroid hormone action that has occurred in recent years has led to the questioning of some long-held dogmas, the confirmation of others and the introduction of several new concepts. These are discussed for individual classes of steroid hormone in separate chapters of this volume. This chapter will take a more general Look at molecular aspects of hormone action with an emphasis on two topics the generality of models of action and specificity of action. 

The metabolism of cholesterol involves modifications to the alkyl side chain and the introduction of substituents onto the phenanthrene ring. A group of enzymes, monooxygenases, plays an important role in catalyzing the formation of bile salts in the liver and steroid hormones in the adrenal gland... 

The discovery of this stereoselective hydroxylation at C-11 and the introduction of diosgenin as a cheap raw material had dramatic effects in reducing the cost of steroid hormones. Thus in the early 1950 s, the price of progesterone dropped within just three years from 80 to 3/g. In its turn cortisone cost about 200/g in 1949 whereas today its cost is less than l/g. Several other steroids are also prepared by processes which include a microbiological oxidation step among them, cortexone and fluocortolone. 

Adrenodoxin Hie enzyme is used in the synthesis of steroid hormones from cholesterol. It is used for the introduction of oxygen atoms into cholesterol in the biosynthetic pathways for aldosterone, the glucocorticoids, and the sex hormones. 

Introduction. This review is based on papers published in I966, and is necessaxily selective in order to keep it short. Some of the newly proposed synthetic procedures are interesting but need further development. Only passing mention will be given to much important work in the field of peptide hormones, since this is covered in the chapter on non-steroidal hormones. 

The book is aimed primarily at university undergraduates, postgraduates and professional chemists who wish to build up their knowledge of terpenoid chemistry. It is intended to serve as a general introduction to the exciting field of terpenoid chemistry. Terpenoids play an important part in all our lives, from perfumes through insect pest control to pharmaceuticals such as steroid hormones and the anti-cancer drug paclitaxel. The subject therefore also serves to illustrate the importance of chemistry in everyday life. 

Introduction - Valuable contributions continue to be made in unfolding the intimate mechanisms of sterol biosynthesis. While the steroid molecule continues to be a useful model for organic synthesis, structural modification of its nucleus has not yielded mammalian hormones with novel or markedly enhanced biological properties. The discovery of new hormones and biologically active substances in the plant and lower animal kingdom has sustained the chemist s interest in steroids. As the chemist adds to the understanding of the role of the steroid hormone in the life process, the biochemist quickens his search for the mechanism of its action. ... 

In this chapter, urinary steroid profiling is discussed first, followed by a description of the state of the art concerning clinical profiling of steroid hormones in plasma by stable isotope dilution (ID) GC-MS. The reason is merely a historical one the art of urinary steroid profiling matured earlier and has found more widespread use. The early attempts to measure plasma steroids by GC-MS were rapidly surpassed by the introduction of immunoassay techniques with which MS could not compete, especially with respect to analytical run time and cost. However, it was not until recently that it was realized that the lack of specificity of immunoassays might initiate a renaissance for clinical MS techniques in steroid analysis. 

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