Mammalian steroid hormone

Terpenoids are structurally based on the isoprenoid (C5) unit and include monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, steroids and carotenoids. These compounds can be further modified to generate greater structural complexity. Thus the saponins are surface active amphiphiles deriving from the glycosylation of steroid (C27) or triterpenoid (C30) entities. Plant triterpenoids with very specific biochemical effects include those that mimic the effects of mammalian steroid hormones or of insect developmental hormones. 

Figure 1. Cytochrome P-450-mediated hydroxylatlon reactions in biosynthesis of major mammalian steroid hormones. (MIT)...

Elkins CA, Mullis LB. Mammalian steroid hormones are substrates for the major RND- and MES-type tripartite multidrag efflux pumps of Escherichia coli. J. Bacteriol. 2006 188 1191-1195. Lin J, Michel LO, Zhang Q. CmeABC functions as a multidrag efflux system in Campylobacter jejuni. Antimicrob. Agents Chemother. 2002 46 2124-2131. 

Tracer studies support the latter mechanism as a likely route for the operation of A -3-oxo-steroid-5a,5 -reduclases in the formation of non-aromatic mammalian steroid hormones. ... 

It will be noted that stigmasterol also represents a commercial route to progesterone. This abundant plant sterol that is readily available from soybean with its C22-C23 double bond, easily converts to progesterone in four steps and has therefore become a preferred substrate for various steroidal drugs. Cholesterol itself, which is the natural substrate for all mammalian steroid hormones, and is readily available from various sources (e.g., wool grease), is now also convertible to desirable steroid intermediates utilizing biotransforma-tion chemistry. The same is true of P-sitosterol (Chapter 11), which is another plant sterol available from soybean. 

From cholesterol 4.18) biosynthesis leads through truncation of the side-chain and other modifications to mammalian steroid hormones, e.g. oestrone 4.22) [11, 33]. Vitamin D3 4.24) is obtainable by photochemically mediated electrocyclic ring-opening of 7-dehydrocholesterol 4.23), followed by a thermal 1,7-sigmatropic hydrogen shift (Scheme 4.7) [34, 35]. The ecdysone insect moulting... 

Oestrogenic activity is not limited to mammalian steroid hormones. In addition to endogenous oestrogens (hormones), a number of exogenous compounds present in foods of plant origin as natural components or substances that get into the food as contaminants (mould metabolites, pesticides and some other substances), also possess oestrogenic activity. These substances resemble the effect of sex hormones and induce oestrus as seen in experimental animals. 

The mammalian and avian immune systems function similarly both incorporate humoral and cell-mediated cytotoxic mechanisms, " and are thought to share a 160m year old relationship with the reptilian immune system. The immune system of mammals shows sexual dimorphism " a greater immune response is normally observed in females, which has been attributed to differences in steroid hormone concentration. In the toad Bufo regularis, sexual dimorphism of the immune system is also apparent. ... 

The female of mammalian species secretes a series of steroid hormones characterized by an aromatic A ring and the lack of a side chain at the 17 position. These compounds serve as regulators in the reproductive processes of the species. The name (estrogens) comes from the fact that in some lower animals the elaboration of this type of compound is directly involved with the phe-... 

Boonyaratanakornkit, V., Melvin, V., Prendergast, P., Altmann, M., Ronfani, L., Bianchi, M.E., Taraseviciene, L., Nordeen, S.K., Allegretto, E.A., and Edwards, D.P. (1998) High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells. Mol. Cell. Biol. 18, 4471 487. 

Examples of co-activators are the steroid receptor co-activator (SRC) family [48] and the components of the mammalian mediator complex, which possesses chromatin remodelling ability and tethers activated steroid hormone receptors to the basal transcription machinery [49]. Additional co-... 

Ketoconazole Blocks fungal P450 enzymes and interferes with ergosterol synthesis Poorly selective interferes with mammalian P450 function Broad spectrum but toxicity restricts use to topical therapy Oral, topical Toxicity and interactions Interferes with steroid hormone synthesis and phase I drug metabolism... 

Reproductive development and function depend on endocrine communication throughout the mammalian life cycle. Protein and steroid hormones, growth factors and other signalling molecules affect gene expression and protein synthesis in target cells of different tissues. In particular, fetal development, development of the reproductive tract,... 

Mammalian cells acquire cholesterol either by de novo synthesis from acetyl-coen-zyme A (CoA) or via the low-density lipoprotein (LDL)-receptor-mediated uptake of LDL particles that contain cholesterol esterified with long-chain fatty acids. These LDL cholesterol esters are subsequently hydrolyzed in lysosomes, after which free cholesterol molecules become available for synthesis of membranes, steroid hormones, bile acids, or oxysterols [1]. 

Cholesterol is doubtless the most publicized lipid, notorious because of the strong correlation between high levels of cholesterol in the blood and the incidence of human cardiovascular diseases. Less well advertised is cholesterol s crucial role as a component of cellular membranes and as a precursor of steroid hormones and bile acids. Cholesterol is an essential molecule in many animals, including humans, but is not required in the mammalian diet—all cells can synthesize it from simple precursors. 

There are many classes of natural and synthetic steroids best known for their wide array of biological activity. The naturally occurring steroids can be subdivided into several categories that include (7) nonhormonal, mammalian steroids (2) vitamin D (. ) hormonal steroids and (4) other naturally occurring steroids. See also Hormones Vitamin and Vitamin D. 

Cholesterol is the most common steroid of mammalian membranes. It is formed biologically from lanosterol, as shown. Ergosterol is the most common steroid of fungal membranes. It differs from cholesterol by the presence of two additional double bonds that affect its three dimensional structure. Also shown are three so-called steroid hormones, andros-terone, estradiol, and testosterone. Note the presence of an aromatic A-ring in estradiol. 

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. 

Cholesterol (Fig. 1.20) is a steroid, the same rigid five-ring backbone used for the mammalian sex hormones. There are only two functional groups an olefin (C-5, C-6) and an alcohol (C-3). The bulk of the molecule can be described as saturated hydrocarbon. There are five methyl groups two are attached to quaternary carbons so they should appear as singlets and three are attached to CH carbons so they should appear as doublets. Most of the protons in the A, B, and C rings can be described as axial or equatorial due to the rigid,... 

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