Estradiol, from testosterone

Estimate the Ki0Vi values at 25°C of the following compounds based on the experimental Ki0Vi values of the indicated structurally related compounds (a) benzoic acid dimethylaminoethyl ester from benzoic acid ethyl ester (log Kiaw = 2.64), (b) the insecticide methoxychlor from DDT (log Ki0Vi = 6.20), (c) the insecticide fenthion from parathion [log Kiow = 3.83, see 111. Ex. 7.2, Answer (d)], and (d) the hormone estradiol from testosterone [log Ki0Vi = 3.32, see 111. Ex. 7.2, Answer (e)]. 

Formation of the Female Sex Hormone Estradiol From Testosterone... 

Fig. 1. Estrogens. Biosynthesis of estradiol from testosterone. Cip and C2(t hydrogens are lost, and C19 is removed as formate. Oxygen incorporated in the first hydroxylation is retained during subsequent oxidations until it appears in the product formate. Oxygen incorporated in the final hydroxylation also appears in the product formate. [J. Fishman Cancer Research (Suppl.) 42 (1982) 3277s-3280is]...

In the biosynthesis of estrone from J -androstenedione, or estradiol from testosterone, or estriol from 17a-hydroxytestosterone (Ryan, 1959), the aromatization of ring A is initiated by reactions designed to remove the angular C-19 methyl group (Meyer, 1955). It is now well-established that the first step is the hydroxylation of this carbon. The progression of reactions beyond this point is not yet clearly defined. However, from information available to date a pathway which appears most probable has been proposed (Fig. 16) (Longchampt et al., 1960b). 

The most significant metabolic product of testosterone is DHT, since in many tissues, including prostate, external genitalia, and some areas of the skin, this is the active form of the hormone. The plasma content of DHT in the adult male is about one-tenth that of testosterone, and approximately 400 ig of DHT is produced daily as compared with about 5 mg of testosterone. About 50-100 ig of DHT are secreted by the testes. The rest is produced peripherally from testosterone in a reaction catalyzed by the NADPH-depen-dent 5oi-reductase (Figure 42-6). Testosterone can thus be considered a prohormone, since it is converted into a much more potent compound (dihydrotestosterone) and since most of this conversion occurs outside the testes. Some estradiol is formed from the peripheral aromatization of testosterone, particularly in males. 

Steroid hormones form a group of pollutants that includes natural hormones such as estradiol, testosterone, and their metabolites as well as several synthetic analogues. Steroid hormones used as growth promoters have already been found in water and sediments (Lai et al. 2000 Thorpe et al. 2003), and their adsorption properties on earth materials have been considered. Lee et al. (2003) report batch experiments where simultaneous sorption of three hormones (17- 3-estradiol, 17-a-ethyl estradiol, and testosterone) on four midwestem U.S. soils and a freshwater sediment were performed. Apparent sorption equilibria were reached within a few hours. Sorption isotherms generally were linear for the chemicals studied on one of these soils (Drummer soil), ranged from 23.4 to 83.2 L kg and log ranged... 

Finlay-Moote O., P.G. Hartel, and M.L. Cabrera (2000). 17 3-Estradiol and testosterone in soil and runoff from grasslands amended with broiler litter. Journal of Environmental Quality 29 1604-1611. 

Despite the distinct advantages of pneumatic nebulizers, ultrasonic nebulizers may alternatively be used, in some instances, with success. In a recent application, a variation of ultrasonic nebulizer called spray nozzle-rotating disk FTIR interface was successfully applied to confirm the presence of methyltestosterone, testosterone, fluoxymesterone, epitestosterone, and estradiol and testosterone cyp-ionate in urine, after solid-phase extraction and reversed-phase LC separation (151). Using a commercial infrared microscopy spectrometer, usable spectra from 5 ng steroid deposits could be readily obtained. To achieve success with this interface, phosphate buffers in the mobile phase were not used because these nonvolatile salts accumulate on the collection disk and their spectra tend to swamp out small mass deposits. Another limitation of the method was that only nonvolatile analytes could be analyzed because volatile compounds simply evaporated off the collection-disk surface prior to scanning. 

The sex hormones estradiol and testosterone are steroids that the body produces from the most abundant steroid of all—cholesterol. 

In women and children, the main effect will be one of virilization in its various forms, ranging from hirsutism and deepening of the voice to enlargement of the female clitoris and male pattern baldness the effect on the voice rapidly becomes irreversible because of changes in the larynx laryngeal polyps have also been observed (69). In women, menstrual abnormalities are likely. Shortterm treatment can produce increases in estradiol, dihydrotestosterone, testosterone (total and unbound), and the ratio of dihydrotestosterone to testosterone. 

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. 

Figure 33.2. Endocrine feedback loops of the mammalian hypothalamic-pituitary-gonadal (HPG) axis. (Adapted from La Barbera A. R. Differentiation and function of the female reproductive system. In Boekelheide, K., Chapin, R. E., Hoyer, P. B., and Harris, C. (Eds.). Comprehensive Toxicology, Vol. 10, Reproductive and Endocrine Toxicology, Elsevier, New York, 1997, pp. 255-272 and Creasy, D. M., and Foster, P. M. D. Male reproductive system. In Haschek, W. M., Rousseaux, C. G. and Wallig, M. A. (Eds.). Handbook of Toxicologic Pathology, 2nd ed., Academic Press, San Diego, 2002,pp. 785-846. E2, estradiol T, testosterone, DHT, dihydrotestosterone, FSH, follicle stimulating hormone LH, luteinizing hormone.

Figure 50-9 The regulatory feedback loop of the hypothalamic-pituitary-gonadal axis. Neural and sensory input from the brain elicits the release of Gn-RH. Gn-RH in turn stimulates the synthesis and release of the gonadotropins FSH and LH, which act on the gonads (ovary and testes) to elicit the ripening and ovulation of the ovary and steroidogenesis (estradiol and progesterone) in the female and spermatogenesis and testosterone production in the male. Inhibin formed by the ovaries and testes along with estradiol and testosterone negatively feeds back to the hypothalamic-pituitary axis to modulate Gn-RH, FSH, and LH release.

Boys with 17fi-hydroxysteroid dehydrogenase deficiency fail to form testosterone from androstenedione, androstenediol fi om DHEA, or estradiol from estrone in a normal manner (see Figure 53-4). At puberty, plasma concentrations of testosterone and DHT are low, and plasma androstenedione and estrone are elevated in those individuals. ... 

Androgens have a 19-carbon nucleus and serve as precursors to more potent analogs produced in the periphery. The adrenal gland can synthesize estradiol and estrone from testosterone and androstene-dione, respectively however, the quantities are extremely small. The rates of production for the various steroids produced by the adrenal gland are listed in Table 74—1. 

Estradiol, an important female hormone, is synthesized from testosterone. Estradiol and progesterone together regulate the monthly changes in the uterus and ovaries that are described collectively as the menstrual cycle (Figure 17.31). 

Testosterone, the testicular hormone, is identified as a male hormone. Estradiol (17/3), which differs from testosterone only by loss of a methyl group and aromatization of ring A, is the ovarian hormone. Progesterone is the progestational hormone and is essential for fertilization and maintenance of pregnancy. Once again medicinal chemists, by further alteration of structures, have made more potent oral and more useful progestins. 

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