Estradiol radioactive

Hormone receptors for steroids were discovered in the early 1960s, when the technology to radioactively mark steroids became available. By obtaining tritium-labeled estradiol, Jensen could show the existence of an intracellular protein component that bound specifically to this hormone and that was called the estradiol receptor (ER). 

Monodisperse microspheres imprinted with theophylline or 17 (3-estradiol were used in competitive radioimmunoassays showing the MIP s high selectivity for the template molecule. In this case the assay is based on the competition of the target molecule with its radioactively labeled analogue for a limited number of antibody binding sites [77,118]. Figure 15 demonstrates that displacing the radioactively marked theophylline from the imprinted polymer was only possible with theophylline as competitor. Structurally related molecules showed effects solely at elevated concentrations [77]. 

Estradiol-17 derived from an implant is indistinguishable from the endogenous esfradiol-17 in the circulatory animal s system. Following administration of radiolabeled estradiol-17 to calves, radioactivity in urine was mainly due to estradiol-17, with much lower amounts of esfrone. Apart of the free forms, both compounds were present as conjugates as well. Radioactivity in feces was primarily due to estradiol-17 and to estradiol-17 and estrone, each compound occurring in the nonconjugated form (1). 

After administration of estradiol benzoate to calves, the major metabolites found in muscle were estradiol-17 and estrone. The pattern of metabolites occurring in fat was similar to that in muscle. Highest residue concentrations were found in kidney and liver, the major metabolites being identified in kidney including estradiol-17, estradiol-17 -glucuronide, estradiol-17, and estrone. In liver, major metabolites could not be identified but estradiol-17, estrone, estriol, and glucuronides accounted for the remaining radioactivity (2). 

Polymers with a molecular weight of about 26000 have been prepared. Their activity is attributed to the slow degradation of the polymeric chain, since after radioactive marking free estradiol could be detected in the urine. 

Figure 1 Autoradiogram of skin treated by the passive application of H-estradiol, in dimethylsulfoxide, for 2 hours. The exposure time was 81 days. (A) A macroscopic view illustrating the regions of the epidermis, hair shafts, and sebaceous glands with the highest levels of radioactivity is shown. (The arrow points at a sebaceous gland.) Penetration gradients of radioactivity are apparent between the epidermis and dermis (B-C) and regions of hair shafts and the hypodermis (D-E). The scale bar is 25 pm. (Reprinted with permission from Ref. 11.)...

Note Estradiol, DDD, and related compounds were strong inhibitors of radioactive estradiol to the receptor. IC50 for the inhibition of [3H]17B-estradiol binding to alligator estrogen receptor of several environmental chemicals are given. 

Tacey, R.L. Harman, W.J. Kelly, L.L. Development of a highly sensitive and specific assay for plasma ethinylestradiol using combined extraction, hquid chromatography and radioinununoassay. J.Pharm.Biomed.Anal., 1994, 12, 1303-1310 [plasma RIA detection SPE LOD 2 pg/mL] Standeven, A.M. Shi, Y.E. Sinclair, J.F. Sinclair, P.R. Yager, J.D. Metabolism of the fiver tumor promoter ethinyl estradiol by primary cultures of rat hepatocytes. Toxicol.Appl.PharmacoL, 1990, 102, 486-496 [gradient UV detection radioactivity detection extracted metabolites]... 

Layne et al. (1964) have shown that radioactive 17a-estradiol excreted by the rabbit after the administration of 16- C-estrone is conjugated at position 17 to... 

Using cell-free homogenates of testis from man, dog, and cat, Rabinowitz (1956) observed the formation of radioactive estradiol-17/8 from radioactive... 

The formation of 2-methoxyestrogens from the estrogens requires also 2-hydroxylation of the phenolic steroids. It has recently been shown by Fishman et al. (1960a) that this reaction does in fact occur in human tissues. Following the injection of estradiol-l7 9-i5-C into a 22-year-old man, 2-hydroxyestrone was isolated from the urine. The extent of 2-hydroxylation appears to be considerable about 12% of the administered radioactivity was recovered from the urine as radioactive 2-hydroxyestrone. An extensive study on 2-hydroxylation of estriol by rat liver in vitro was carried out by King (1961 a,b). It was found that the 2-hydroxylase activity is limited to the microsomal fraction and requires either NADHj or NADPHz, and possibly a folic acid derivative ATP appears to stimulate the 2-hydroxylase. 

In 1957, Mueller and Rumney showed that, when estradiol-17 9-76-C was incubated under aerobic conditions with mouse liver microsomes and NADPH2, a number of radioactive products more polar than estradiol-17/3 were formed. One of the products proved to be identical with 6-0x0-estradiol-17/3, whereas the two remaining phenolic substances were identified as 6 -hydroxyestrone and 6 j3 -hydroxycstradiol-17/9. Breuer et al. (1959a) next detected the same metabolites after incubation of estradiol-17/3 or estrone with rat liver slices. When these experiments were carried out, the absolute configuration of the 6-hydroxy group in the 6-hydroxy-estradiol-17/3 which served as a reference compound was unknown. The reference sample of 6-hydroxyestradiol-17/3 had been obtained by boro-hydride reduction of 6-oxoestradiol-17/8 (Longwell and Wintersteincr,... 

There is little question that the site of steroid conversions is intracellular. Complete removal of follicle cells which remain adherent to oocytes after manual dissection from their follicles does not alter chromatographic profiles, either quantitatively or qualitatively. Likewise, the profiles obtained from oocytes injected with radioactive progesterone were essentially identical to those obtained by incubation of oocytes with exogenous hormone. Thus, the observations reveal a heretofore unsuspected capability of oocytes to participate in steroid metabolism. This is not restricted to Bana pipiens, but also has been observed in Xenopus laevis and Rana catesbiana. Likewise, both exogenous deoxycorticosterone and estradiol are metabolized by isolated oocytes, giving rise to different kinds of metabolites than obtained with progesterone (Reynhout and Smith, 1973). 

This key problem was solved in 1985 by Jaouen et ai, who were able to stabilize Cr(CO)3 derivatives of estradiol and, by using radioactive complexes, to confirm the identity of ERa as the primary target of these organometallic... 

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