17-ketosteroids and dihydroequilin

The absorption of equilin sulfate and equilin from the gastrointestinal tract was determined in normal men after the ingestion of [3H]equilin-[35S]sulfate or a mixture of [3H]equilin and equilin-[35S]sulfate, while the metabolism of equilin sulfate was investigated after iv administration of [3H]equilin sulfate to postmenopausal women. After the oral administration of [3H]equilin-[35S]sulfate, equilin sulfate containing both 3H and 35S was isolated from plasma; however, only in the first sample taken at 10 min was the 3H/35S ratio the same as that of the [3H]equilin-[35S]sulfate ingested. The 3H/35S ratio then increased, and by 12 h only traces of equilin-[35S]sulfate were detectable. Similarly, after the ingestion of [3H]equilin and equilin-[35S]sulfate, [3H]equilin-[35S]sulfate was isolated from plasma. The 3H/35S ratio was at all time points greater than the 3H/35S ratio of the ingested mixture. Analysis of urine indicated that over 98% of 35S was not associated with any steroid and was most likely inorganic sulfate. After iv administration of [3H] equilin sulfate to postmenopausal women, equilin, equilenin, 17 beta-dihydroequilin, and 17 beta-dihydroequilenin were isolated from the urine. These results indicate that 1) some of the orally administered equilin sulfate was absorbed from the gut without prior hydrolysis, 2) some equilin sulfate was hydrolyzed in the gut before absorption; 3) equilin was absorbed more efficiently than equilin sulfate; 4) equilin absorbed was readily sulfated and circulated in this form; and 5) equilin sulfate was extensively metabolized, and the metabolites were excreted in the urine mainly conjugated with glucuronic acid.

Topics: 17-Ketosteroids; Administration, Oral; Age Factors; Digestive System; Equilenin; Equilin; Female; Humans; Injections, Intravenous; Intestinal Absorption; Male; Menopause; Middle Aged

The MCRs of equilin sulfate and equilin were determined in normal postmenopausal women and a normal man by single iv injections of either [3H]equilin sulfate or [3H] equilin. After the administration of [3H]equilin sulfate, blood was drawn at various time intervals, and the plasma obtained was fractionated into the unconjugated, sulfate, and glucuronide fractions. The bulk of radioactivity was present in the sulfate fraction, and from this, [3H]equilin sulfate, [3H]17 beta-dihydro-equilin sulfate, [3H]equilenin sulfate, and [3H]17 beta-dihydroequilenin sulfate were isolated and purified, and their concentrations were measured. The disappearance of radioactivity from plasma as equilin sulfate can be described as a function that is the sum of two exponentials. The initial fast component (half-life, 5.2 +/- 1.2 min) represents distribution and transfer from a space, with a mean volume of 12.4 +/- 1.6 liters. The mean value for the rate constant of total removal from the initial volume is 163 +/- 19 U/day, of which 15.8 +/- 2% is irreversible. The mean half-life of the slower component of equilin sulfate is 190 +/- 23 min, and the mean MCR is 176 +/- 44 liters/day . m2. Similarly, after the administration of [3H]equilin to a normal postmenopausal woman and a man, the disappearance of radio-activity from plasma as equilin could be fitted by a single straight line, consistent with a one-compartment system. The half-life of equilin was approximately 19-27 min, and the MCR of equilin was calculated to be 1982 liters/day/m2 in the normal man and 3300 liters/day/m2 in the normal postmenopausal woman. The bulk of [3H]equilin was very rapidly metabolized to mainly equilin sulfate. Small amounts of 17 beta-dihydroequilin sulfate and 17 beta-dihydroequilin were also isolated from the plasma. The in vivo formation of 17 beta-dihydroequilin and its sulfate may be of importance, as this estrogen is approximately 8 times more potent as a uterotropic agent than equilin sulfate.

Topics: 17-Ketosteroids; Adult; Equilenin; Equilin; Estrogens, Conjugated (USP); Female; Humans; Kinetics; Male; Menopause; Metabolic Clearance Rate; Middle Aged

[3H]Equilin [3H-labeled 3-hydroxy-1,3,5(10), 7-estratetraen-17-one] was administered iv to a pregnant mare in the 10th month of gestation. Maternal urine was collected for 3 days, and blood samples were taken 35 min and 3, 6, 12, and 24 h after the injection. The half-life of the disappearance of radioactivity from the blood was approximately 2.5 h. Over 90% of the administered dose was excreted in the first 24 h. The urine was extracted, hydrolyzed, and fractionated. The bulk of the radioactive material (75%) was present in the phenolic sulfate fraction from which radiochemically pure equilin, equilenin [3-hydroxy-1,3,5(10),6,8-estrapentaen-17-one], 17 alpha-dihydroequilin [1,3,5(10), 7-estratetraen-3,17 alpha-diol], 17 beta-dihydroequilin [1,3,5-(10,7-estratetraen-3,17 beta-diol], 17 alpha-dihydroequilenin [1,3,5(10),6,8-estrapentaen-3,17 alpha-diol], and 17 beta-dihydroequilenin [1,3,5(10),6,8-estrapentaen-3,17 beta-diol] were isolated and identified. Except for equilenin, the above-named steroids were also isolated and identified from the glucuronide fraction. Along with these estrogens, the two classical estrogens, estrone and 17 alpha-estradiol, were also isolated, but both of these estrogens were devoid of any radioactivity. These results indicate that 1) the B ring unsaturated estrogens are not metabolized to the B ring saturated estrogens (classical estrogens), 2) all of the B ring unsaturated estrogens isolated and identified from the pregnant mare's urine are metabolites of equilin, 3) the major metabolite of equilin excreted in the urine was equilin sulfate, 4) from the specific activity of the isolated equilin sulfate and the amount of [3H]equilin injected, the secretion rate of equilin was calculated to be 96 mg/24 h, and 5) the major reduced metabolites of equilin are the biologically less active 17 alpha-reduced products.

Topics: 17-Ketosteroids; Animals; Equilin; Estradiol; Estrone; Female; Glucuronates; Horses; Pregnancy; Pregnancy, Animal

Topics: 17-Ketosteroids; Animals; Cross Reactions; Equilin; Estrogens, Conjugated (USP); Female; Haptens; Horses; Humans; Immune Sera; Methods; Radioimmunoassay; Steroids