Hormones diethylstilbestrol

Pitocin, a hormone, was reported to increase lipolysis (Kelly 1943, 1945), and another hormone, diethylstilbestrol, is said to increase lipase activity toward tributyrin but not toward milk fat (El-Nahta 1963). 

An bolic hormon l-type growth promoters Diethylstilbestrol 1972-1991... 

ANABOLIC HORMONAL-TYPE GROWTH Diethylstilbestrol Bovine muscle... 

Use of hormonal-type substances for growth promotion and fattening purposes in food-producing animals is prohibited or restricted in many countries. Administration of diethylstilbestrol, in particular, has been totally banned worldwide. This implies that adequate analytical methods should be available for regulatory control. Due to its sensitivity, radioimmunoassay has have become most important in diethylstilbestrol analysis and represents the final detection step in the EU reference method for stilbene residues analysis (100). 

In some instances, combinations of Cig and silica columns are also used for better purification of the crude extracts (431, 445). A combination of Cg, silica, and amino solid-phase extraction columns has been successfully employed to fractionate anabolic and catabolic steroid hormone residues from meat in polar and nonpolar neutral and phenolic compounds, and to purify further each fraction effectively (452). Another combination of two solid-phase extraction columns, one using a graphitized carbon black sorbent and the other Amberlite resin in the hydroxyl form, allowed neutral anabolics to be isolated and separated from acidic anabolics and their metabolites (453). A combination of basic alumina column placed in tandem with an ion-exchange column has also been applied for the purification of the crude extracts in the determination of diethylstilbestrol and zeranol (427), and estradiol and zeranol in tissues (450). 

Diethylstilbestrol continues to be recommended in some centers as one of the agents of last resort when prostate cancer proves refractory to steroid hormones or androgen deprivation therapy has done all it can (1). In a Japanese study in which 16 patients were given a daily intravenous injection of diethylstilbestrol diphosphate 250 mg for 28 days, the short-term response was favorable and the drug was well tolerated (2). 

In a randomized study of men treated hormonally for prostatic cancer (3), cardiovascular adverse effects were reported more often in patients treated with diethylstilbestrol than in those treated with cyproterone acetate. The risk was highest during the first 6 months of treatment. 

Initiatives by medical researchers, by DES Action, and by the Public Citizen s Health Research Group secured funding in the USA for medical research on the prevalence of cancer and other effects in the young women who had been exposed in utero, and eventually also the men. The US National Institute for Environmental Health Sciences (NIEHS) has been one of the centers for toxicological studies of the effects of diethylstilbestrol. A substantial amount of research on the effects of diethylstilbestrol— animal experiments as well as epidemiological studies— has produced a valuable body of knowledge about how hormones affect the development of the fetus and prime the individual for disease later in life. 

A further follow-up and analysis of 3879 women, taken from two earlier US studies, who had been exposed to diethylstilbestrol during pregnancy has been presented (42). The results showed a modest association between diethylstilbestrol exposure and the risk of breast cancer (RR = 1.27 95% Cl = 1.07,1.52). The increased risk was not further aggravated by a family history of breast cancer, by use of oral contraceptives, or by HRT. There was no evidence that diethylstilbestrol was associated with a raised risk of ovarian, endometrial, or other hormone-associated cancers. 

The effects of in-utero exposure to diethylstilbestrol on the menstrual cycle have been studied prospectively in 198 women and in 162 unexposed controls (44). A major limitation of this study was the exclusion of women with a severe menstrual abnormality. Exposure to diethylstilbestrol was associated with a statistical significantly lower duration of menstrual bleeding but not with dysmenorrhea. For most women exposed to diethylstilbestrol, any effects on reproductive hormonal function are in all probability minor, if present at all. 

Takezawa Y, Nakata S, Kobayashi M, Kosaku N, Fukabori Y, Yamanaka H. Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer. Scand J Urol Nephrol 2001 35(4) 283-7. 

Michinaga S, Ariyoshi A. High-dose intravenous diethylstilbestrol diphosphate therapy for hormone-refractory prostate cancer. Nishinihon J Urol 2002 64 203-5. 

The dextran-coated charcoal (DCC) assay measures the hormone-binding capacity of the cytosol fraction of the tumor tissue (Lee and Chan, 1994). Fresh tissue (more than 100 mg) is immediately frozen, homogenized, and the cytosol fraction is extracted. Aliquots of the cytosol are incubated with radiolabeled [3H] estradiol with and without 100-fold molar excess of nonradiolabeled competitor (diethylstilbestrol) to displace radiolabeled steroid from the low-capacity specific binding sites (ER), but not from the high-capacity nonspecific binding sites in the cytosol. The unbound steroid is removed by selective adsorption on DCC. 

Figure 8.11 Separation of a mixture of human hormones (a) total ion current (TIC) profile (b) UV profile (254 nm). Conditions injection volume, 60 nl capillary, 25 cm x 250 /xm I.D. PEEK capillary, C18, 5 /xm flow rate, 1 /xl/min gradient, 40-80% acetonitrile in 25 min. Peaks 1, nortestosterone 2, testosterone 3, diethylstilbestrol 4, methyltestosterone 5, medroxyprogesterone , diethylstilbestrol impurity. (Reprinted from Ref. 26 with permission.)...

C9. Chang, A., Yeap, B., Davis, T., Blum, R., Hahn, R., et al., Double-blind, randomized study of primary hormone treatment of stage D2 prostate carcinoma Flutamide versus diethylstilbestrol. J. Clin. Oncol. 14, 2250-2257 (1996). 

R9. Robertson, C. N., Roberson, K. M., Padilla, G. M., O Brien, E. T., Cook, J. M., etal., Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J. Natl. Cancer... 

The natural female steroid hormone with the greatest estrogenic activity is 17C-estradiol. It is important to note that some synthetic estrogens, such as diethylstilbestrol (DES), moxestrol, and ll)8-chloromethyl estradiol show 10 times more estrogenic activity than 17)8-estradiol in the E-SCREEN assay [136]. Ethinylestradiol has the same estrogenic activity as 17/1-estradiol, whereas the activity of the synthetic EDCs is by some orders of magnitude lower [136]. In this context it is important to note that most, if not all, efflu-... 

It is important to investigate the bioconcentration potential of natural hormones, such as 17 -estradiol, estrone (using or tritium labeled compounds) and synthetic hormones (e.g., mestranol, diethylstilbestrol etc.). However, the concentration in the water should be at environmental relevant concentrations (< 10 ng 1 ). 

In contrast, prooxidant effects of estrogens have been established in other model systems. 17(3-estradiol or other estrogens induce single-strand breaks or 8-hydroxylation of guanine bases of DNA in Syrian hamsters treated with these hormones. Moreover, metabolites of estrogen or diethylstilbestrol in the presence of peroxidase and DNA induce 8-hydroxylation... 

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