17 -Estradiol

in both the gender and reproductive meaning of the word. The sex hormones determine whether an animal is male or female, and also the relative amounts of the different sex hormones determine the sexual characteristics of that animal, such as how masculine or feminine they appear and behave. 

That s the most important one, along with estrone and estriol, which are less potent. They are all based on the standard four-ring steroid structure, with just minor differences in side groups. And this includes testosterone too. It s quite amazing that all the differences between male and female come down to something as trivial as the side group of a molecule  

Testosterone - the male hormone. Note the difference with estradiol is only an extra methyl group, the OH has been oxidized to a ketone, and the phenyl ring reduced 

Although it can be produced by many cells in the body, including fat cells, in the brain and in artery walls (in males as well as females), most estradiol is synthesized in the ovaries from compounds derived from cholesterol (see p91). 

It helps a woman prepare for pregnancy, by supporting the reproductive organs, keeping the eggs healthy in the ovaries, and instigating the monthly ovulation and menstrual cycle. 

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Figure 10.3-25. a) Structure of diethylstilbestrol (DES) b) 3 D pharmacophore query of DES two hits were found c) estrone and d) estradiol. 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Testosterone promotes muscle growth deepening of the voice the growth of body hair and other male secondary sex characteristics Testosterone is formed from cholesterol and IS the biosynthetic precursor of estradiol the principal female sex hormone or estrogen Estradiol is a key substance m the regulation of the menstrual cycle and the reproductive process It is the hormone most responsible for the development of female secondary sex characteristics... 

Testosterone and estradiol are present m the body m only minute amounts and their isolation and identification required heroic efforts In order to obtain 0 012 g of estradiol for study for example 4 tons of sow ovaries had to be extracted ... 

The compound shown is diethylstilbestrol (DES) it has a number of therapeutic uses in estrogen replacement therapy DES is not a steroid but can adopt a shape that allows it to mimic estrogens such as estradiol (p 1100) and bind to the same receptor sites Construct molecular models of DES and estradiol that illustrate this similanty in molecular size shape and location of polar groups... 

Commercial products approved by the Food and Dmg Administration iaclude the naturaHy occurring hormone estradiol [50-28-2] (Compudose)... 

Very Htfle data are available regarding effects of anaboHc steroid implants on the Hpid metaboHsm in growing mminants. Lipogenic enzyme activity and fatty acid synthesis in vitro were elevated in subcutaneous adipose tissue from bulls implanted with estradiol (44), which may account for the increase in fat content of carcasses reported in some studies. TBA implants have no effect on Hpogenesis in intact heifers, and only tend to reduce Hpogenic enzyme activities in ovariectomized heifers (45). 

Withdrawal from anaboHc steroid treatment is not required before slaughter because residue levels in edible tissues are negligible, and are significantly lower than other sources of estradiol such as the normal endogenous production in humans and the phytoestrogens consumed in plant food sources (1). 

Estrogens are a group of naturally occurring steroid sex hormones which are characterized by their ability to induce estms in the female mammal. They are derivatives of the planar tetracycHc stmcture estra-l,3,5(10)-trien-3-ol [53-63-4](V) and the three principal estrogens in humans are estrone [56-16-7] (E ) (2), estradiol [50-28-2] (E2) (3), andestriol [50-27-1] (E ) (4). 

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. 

Diethylstlbestrol [56-53-1] (DES)(7), which was first synthesized in the 1930s, is the most widely studied nonsteroidal estrogen and has been extensively reviewed. It is an extremely potent estrogen, possessing four times the oral potency of estradiol (3), but carcinogenicity problems have limited its use. 

WS-7528 [132147-69-4][VI] a nonsteroidal estrogen, is an isoflavone which has been isolated from Streptomjces sp. No. 7528 and is an estrogen agonist. It inhibits [3ff]-estradiol binding to its receptor in rat uterine cytosol at an inhibitor for 50% of the rats tested (IC q) concentration of 5.7 nM. It also induces the growth of estrogen-dependent human breast cancer cell line MCE-7 (7). 

A stmcturally related series of phenyfiiydrazones resulted ia the selection of compound A-007 [2675-35-6] (DEKK-TEC)(37) for the treatment of hormone-dependent tumors. A-007 is an antiestrogen that, ia contrast to tamoxifen, demonstrated inhibitory activity both ia the presence and absence of estradiol ia ZR-75-1 estrogen-dependent human breast cancer cells, and afforded more protection than tamoxifen ia the 7,12-dimethylbenz[i7]anthracene... 

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