Estrone and estradiol

Although estrone and estradiol (26) have both been isolated from human urine, it has recently been shown that it is the latter that is the active compound that binds to the so-called estrogen receptor protein. Reduction of estrone with any of a large number of reducing agents (for example, any of the complex metal hydrides) leads cleanly to estradiol. This high degree of stereoselectivity to afford the product of attack at the alpha side of the molecule is characteristic of many reactions of steroids. 

Although both estrone and estradiol are available for replacement therapy, they suffer the disadvantage of poor activity on oral administration and short duration of action even when administered parenterally, because of ready metabolic disposition. In order to overcome these deficiencies, there was developed a series of esters of estradiol with long-chain fatty acids. These esters are oil-soluble and correspondingly water-insoluble compounds. 

The ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). 

Polyphenols and flavanoids in rat liver microsomal fractions have been demonstrated to inhibit glucuronidation of estrone and estradiol in vitro (Zhu et al, 1998). In addition, flavonoids have also been found to induce phase I and II enzymes in rats including UDP-glucuronosyl transferase (Seiss et al, 1996). However, the effects of phytoestrogens have not been evaluated for either their inhibition or induction of glucuronosyl transferase activity. 

SCHEME 10.11 Estrone and estradiol are oxidized to catechols and o-quinones, which isomerizes to /j-QMs. 

A series of experiments was also conducted by Bowman et al. [34] to ascertain the effects of differing environmental factors on the sediment-water interactions of natural estrogens (estradiol and estrone) under estuarine conditions. Sorption onto sediment particles was in this case relatively slow, with sorption equilibrium being reached in about 10 and 170 h for estrone and estradiol, respectively. On the other hand, true partition coefficients calculated on colloids were found to be around two orders of magnitude greater that those on sediment particles. Hence, it was concluded that under estuarine conditions, and in comparison to other more hydrophobic compounds, both estrone and estradiol... 

Estriol, etjuilin, estrone, and estradiol AgNQ, ILO-MeOH (40 60). Octsiiecyl 24 ... 

The ovary normally ceases its gametogenic and endocrine function with time. This change is accompanied by a cessation in uterine bleeding (menopause) and occurs at a mean age of 52 years in the USA. Although the ovary ceases to secrete estrogen, significant levels of estrogen persist in many women as a result of conversion of adrenal and ovarian steroids such as androstenedione to estrone and estradiol in adipose and possibly other nonendocrine tissues. 

Nelson et al. [60] published a method for estrone and estradiol measurement using the dansyl derivatives with analysis by APCI. After adding di-estrone and ck-estradiol to 0.5 ml serum, the steroids are extracted with 6 ml methylene chloride. After drying the solvent, 50 pi of sodium bicarbonate and (100 mmol/1, pH 10.5) 50 pi of dansyl chloride (1 g/1) are added. The samples can be injected after heating at 60 C for 1 min. 

The routine measurement of estrone and estradiol by immunoassay techniques has also given rise to the familiar problems of poor sensitivity, cross-reactivity, and poor intermethod reproducibility. Most automated methods cannot measure these steroids in sera of children and men. Development of LC-MS/MS methods has also proven challenging as most investigators have found that estrone and estradiol are poor ionizers and the desired sensitivity has not been achieved. The Mayo group [60] published the LC-MS/MS quantification of estradiol and estrone using dan-syl chloride derivatives (described above) and 2H5 estradiol and 2H4 estrone internal standards. 

Quest diagnostics also provide commercial estrone and estradiol measurement by MS/MS and their normative data are listed in Table 5.3.1. 

Hormones detected in milk include some from the peptide and steroid classes but none of the amino hormones. Prolactin, a protein of 199 amino acid residues, is normally present in a concentration of about 50 /tg/liter, and the hexapeptide gonadotropin-releasing hormone of the hypothalmus at about 1.5 g/liter. Steroid hormones from the adrenal cortex include the glucocorticoids cortisol and corticosterone, totaling 0.2-0.6 /tg/liter. Those from the ovary—progesterone, estrone, and estradiol—have concentrations of 10-30, 30, and 175 /ig/liter, respectively. Hormones in milk have been reviewed by Koldovsky (1980) and Pope and Swinburne (1980). The prolactin in milk is biologically active (Gala et al. 1980). 

Ramanathan, R., Cao, K., Cavalieri, E., and Gross, M. L. (1998). Mass spectrometric methods for distinguishing structural isomers of glutathione conjugates of estrone and estradiol. J. Am. Soc. Mass Spectrom. 9 612-619. 

Modic, W.M. (2004). The Role of Testicular Aromatase in the Atrazine Mediated Changes of Estrone and Estradiol the Male Wistar Rat. Thesis submitted to North Carolina State University. Department of Molecular Structural Biochemistry, Raleigh, NC,... 

Yamashita K, Okuyama M, Watanabe Y, Honma S, Kobayashi S, NumazawaM (2007) Highly sensitive determination of estrone and estradiol in human serum by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids 72 819-827... 

Since the neutral molecules of steroid hormones and metabolites are not easily ionized under either APCP or ESI+/ modes, LC-MS/MS is less sensitive when used directly in either APCP or ESI+/ modes, with LOQs at ng/mL level as shown in Table 4 [20, 21, 52], It has been observed that estrone, 16a-hydroxyestrone, 2-methoxyestrone, 4-methoxyestrone, and 2-hydroxy-3-methoxyestrone are sensitive to APCI+ mode, while 2-hydroxyestrone and 4-hydroxyestrone are sensitive to APCI- mode, and even more sensitive to ESI mode [29], Estrone, estradiol, estradiol, and estriol are sensitive to ESI" mode, and testosterone is sensitive to ESP mode [76, 77], Similarly, estrone and estradiol are sensitive to APPI" mode, and testosterone is sensitive to APPI+ mode with LOQs in a range of 1.5-10 pg/mL [22], which are comparable with those steroid hormones and metabolites derivatized with hydroxylamine or dansyl chloride, and detected under ESP mode [2, 8],... 

Antibodies. The antibody A-1 against estrone and estradiol-17/8 was raised in a sheep against estradiol-17/3 coupled at C-17 to bovine serum albumin. At 50% displacement of tritiated estradiol-17/8, the cross-reac-... 

After diethyl ether extraction from 1-ml serum samples and chromatography on Sephadex LH-20 columns, estrone and estradiol-17/3 were estimated after incubation by the method of Hotchkiss et al. with antibody A-1. 

TABLE IV Influence of the Duration of Contact of the Incubates with the Minicolumns on the Amount of Antibody-Bound Tritiated Estrone and Estradiol-17/8 Passing through the Sephadex G-25 Fine Minicolumns" ... 

Antibody A-1 was incubated with untritiated estrone and estradiol-17/3 in amounts of 0 pg and 100 pg and with the same tritiated estrogen, respectively. 

---