DISTRIBUTION AND METABOLISM OF IODO-α-ESTRADIOL LABELED WITH RADIOACTIVE IODINE

Iodohexestrols. II. Characterization of the binding and estrogenic activity of iodinated hexestrol derivatives, in vitro and in vivo

“…It is apparent that the pattern of uptake and retention by the uterus, pituitary, and mammary tissue differs little from that of control tissues, such as liver, stomach, kidney, and spleen. The major portion of radioactivity is found in the gut (and gut contents, not shown) where it appears initially in the small intestine and later in the colon and cecum; pronounced enterohepatic circulation is typical for estrogen distribution and elimination (Slaunwhite et al, 1973) and was previously noted by Albert et al (1949) in his study of iodinated estradiols. From the progressively increasing uptake by the thyroid, it is apparent that some free iodide is being produced through metabolism; the thyroid uptake, 3 Female rats (20-weeks old) were ovariectomized 19 hr prior to i.v.…”

“…) Aliphatic iodine compounds have a high susceptibility toward substitution and elimination reactions (Gould, 1959); therefore, on the grounds of chemical stability, we considered it preferable to have the iodine bonded to an aryl group. The preparation of both 2-and 4-monoiodo-17/3-estradiol and 2,4-diiodo-17/3-estradiol (Albert et al, 1949;Hillmann-Elies et al, 1953;Nambara et al, 1971; Matkovics et al, 1971) had been reported. Although the iodine in these derivatives appeared to be metabolically stable, these compounds showed either low or negligible uterotrophic activity (Albert et al, 1949;Hillmann-Elies, 1953;Peck et al, 1961), and they were not taken up selectively by the uterus (Albert et al, 1949).…”

“…The preparation of both 2-and 4-monoiodo-17/3-estradiol and 2,4-diiodo-17/3-estradiol (Albert et al, 1949;Hillmann-Elies et al, 1953;Nambara et al, 1971; Matkovics et al, 1971) had been reported. Although the iodine in these derivatives appeared to be metabolically stable, these compounds showed either low or negligible uterotrophic activity (Albert et al, 1949;Hillmann-Elies, 1953;Peck et al, 1961), and they were not taken up selectively by the uterus (Albert et al, 1949). It is not certain whether this was the result of the failure to satisfy criteria 2 or 3, but as the estrogen receptor is known to be relatively intolerant of bulk at A-ring positions 2 and 4 (Katzenellenbogen et al, 1973b), it appeared that functionalization of these positions in a steroidal ligand was not consistent with high receptor binding (criterion 2).…”

Iodohexestrols. I. Synthesis and photoreactivity of iodinated hexestrol derivatives

“…o-iodophenol is reported to be ca. five times faster than conversion of the o-iodophenol to a o.o'-diiodophenol (Mayberry, 1967), we have found that the successive iodination reactions of hexestrol ( 1) are sufficiently similar in rate that treatment of hexestrol with 1 equiv of iodine in aqueous ammonium hydroxide-methanol (Albert et al, 1949) produces a mixture of starting material and the five possible orthoiodinated derivatives 2-6 (Scheme I) in the molar ratio 10: 3:2.5:2:1. Iodination with iodine monochloride in acetic acid (Wallingford and Krueger, 1949) tended to give more highly substituted products and was less convenient.…”