Estrogens, steroidal

Stern plane Sternutators Steroid Steroid acids Steroidal antiestrogens Steroidal estrogens... 

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. 

Through fractionating WWTW effluents and screening those fractions with cell-based bioassays responsive to estrogens, the natural steroidal estrogens Ej and... 

The sheer complexity of environmental mixtnres of EDCs, possible interactive effects, and capacity of some EDCs to bioaccumulate (e.g., in fish, steroidal estrogens and alkylphenolic chemicals have been shown to be concentrated up to 40,000-fold in the bile [Larsson et al. 1999 Gibson et al. 2005]) raises questions about the adequacy of the risk assessment process and safety margins established for EDCs. There is little question that considerable further work is needed to generate a realistic pictnre of the mixture effects and exposure threats of EDCs to wildlife populations than has been derived from studies on individual EDCs. Further discussion of the toxicity of mixtures will be found in Chapter 2, Section 2.6. 

Jobling, S., Williams, R., and Johnson, A. et al. (2006). Predicted exposures to steroid estrogens in U.K. rivers correlate with widespread sexual disruption in wild fish populations. Environmental Health Perspectives 114, 32-39. 

Thorpe, K.L., Cummings, R.I., and Hutchinson, T. et al. (2003). Relative potencies and combination effects of steroidal estrogens in fish. Environmental Science and Technology 37, 1142-1149. 

Russo, J. Russo, I. H. Genotoxicity of steroidal estrogens. Trends Endocrinol. Metab. 2004, 15, 211-214. 

Lai KM, Johnson KL, Scrimshaw MD, Lester JN (2000) Binding of waterborne steroid estrogens to solid phases in river and estuarine systems. Environ Sci Technol 34 3890-3894... 

Hanselman TA, Graetz DA, Wilkie AC, Szabo NJ, Diaz CS (2006) Determination of steroidal estrogens in flushed dairy manure wastewater by gas chromatography-mass spectrometry. J Environ Qual 35 695-700... 

Andersen HR, Hansen M, Kjolholt J, Stuer-Lauridsen F, Temes T, Halling-Sorensen B (2005) Assessment of the importance of sorption for steroid estrogens removal during activated sludge treatment. Chemosphere 61 139-146... 

Braga O, Smythe GA, Schafer AI, Feitz AJ (2005) Fate of steroid estrogens in Australian inland and coastal wastewater treatment plants. Environ Sci Technol 39 3351-3358... 

Koh YKK, Chiu TY, Boobis AR, Scrimshaw MD, Bagnall JP, Soares A, Pollard S, Cartmell E, Lester JN (2009) Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes. Environ Sci Technol 43 6646-6654... 

In order to review these putative relationships it is first useful to define a subset of well-characterized hormones and neurotransmitters that have been implicated in behavior. The chemicals selected for discussion here are among those for which a robust relationship with behavior has been proposed, including steroids (estrogens, progestins, androgens and glucocorticoids), proteins (prolactin) and the neuropeptides (oxytocin and vasopressin). All of these chemicals may act as hormones, neurotransmitters and/or neuromodulators. In addition, to understand the action of these hormones, it is helpful to be familiar with some of the more common neurotransmitters (described below). Space does not permit a discussion of the behavioral effects of many additional compounds with endocrine or paracrine properties. 

While differing significantly from steroid estrogenic hormones in terms of structure, this drug exhibits all of the characteristic biological properties as these hormones. Hexestrol is used for the same indications as estrone. It is also used for prostate cancer or its hypertrophy in men. Synonyms of this drug are sin-estrol, cycloestrol, and others. 

Aromatase catalyzes the conversion of C19 steroids (androgens) into Cig steroids (estrogens) containing a phenolic A ring (Scheme 3.1). It is an enzyme complex comprised of two proteins. One is nicotinamide adenine dinucleotide phosphate... 

Fosfestrol is indicated in the treatment of carcinoma of the prostate. It is a synthetic non-steroidal estrogen which is dephosphorylated to stilboestrol. Polyestradiol phosphate is an oestrogen with sustained activity that is exclusively used for prostate cancer. It is stored in tissues and slowly dephosphorylated to estrogen. 

Synthetic steroid hormones retain the common steroid nucleus, but they may contain novel substituents that affect their pharmacological activity. The two most widely used synthetic steroid estrogens are ethinyl estradiol (Estinyl) and mestranol, found in oral contraceptives. Synthetic steroids containing an ethinyl substitution are metabolized more slowly. Thus, these synthetic steroid hormones have better oral absorption properties and extended biological half-lives than the natural estrogens. 

Approximately 50% of a dose of mestranol is de-methylated to form ethinyl estradiol. Ethinyl estradiol also can be deethinylated. Subsequently, the metabolism of these two synthetic estrogens proceeds by means of the same pathways as the natural steroid hormones. The principal metabolites of mestranol and ethinyl estradiol are hydroxylated derivatives that are conjugated with either glucuronic acid or sulfate. The synthetic steroid estrogens, in contrast to the natural estrogens, are excreted primarily in the feces. 

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