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At least 19 recordsLinked to original sources
PubMed1989

Metabolism of [3H]equilin-[35S]sulfate and [3H]equilin sulfate after oral and intravenous administration in normal postmenopausal women and men.

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.

17-Ketosteroids↗
PubMed1983

Pharmacokinetics of equilin and equilin sulfate in normal postmenopausal women and men.

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.

17-Ketosteroids↗
PubMed1993

Metabolic clearance rate of equilin sulfate and its conversion to plasma equilin, conjugated and unconjugated equilenin, 17 beta-dihydroequilin, and 17 beta-dihydroequilenin in normal postmenopausal women and men under steady state conditions.

The constant infusion of [3H]equilin sulfate ([3H]EqS) was used to estimate the MCR of equilin sulfate (EqS) and to measure the conversion of this estrogen to equilin (Eq), equilenin (Eqn), equilenin sulfate (EqnS), 17 beta-dihydroequilin (17 beta-Eq), 17 beta-dihydroequilin sulfate (17 beta-EqS), 17 beta-dihydroequilenin (17 beta-Eqn), and 17 beta-dihydroequilenin sulfate (17 beta-EqnS) in normal postmenopausal women and men. Infusion of [3H]EqS was started in five postmenopausal women and two men 30 min after a priming dose and continued at a constant rate of 12-15 microCi/h for 3 h. Blood samples were taken 15 min before the end of infusion, at the end of the infusion, and 15 min after the end of infusion. Unconjugated and sulfate-conjugated Eq, Eqn, 17 beta-Eq, and 17 beta-Eqn were isolated from plasma. The mean MCR of EqS was calculated to be 280 +/- 24 L/day or 170 +/- 18 L/day.m2. The mean conversion ratios for precursor EqS to product 17 beta-EqS, EqnS, 17 beta-EqnS, 17 beta-Eq, Eq, Eqn, and 17 beta-Eqn were 0.300, 0.190, 0.100, 0.020, 0.016, 0.008, and 0.004 respectively. In both the sulfate-conjugated and unconjugated forms, 17 beta-Eq was the most abundant metabolite formed. 17 beta-Eq estrogen is a potent uterotropic agent and has a much higher affinity for estrogen receptors than Eq. Its formation may be of importance in the overall biological activity of EqS present in conjugated equine estrogen preparations.

Aged↗
PubMed1995

Metabolism of equilin sulfate in the dog.

The metabolism of equilin sulfate was determined in female dogs receiving 2.5 mg/kg of [3H]equilin sulfate alone or in a preparation that contained all the components that are present in the conjugated equine estrogen product Premarin. The pharmacokinetic parameters of total radioactivity indicated that the drug is rapidly absorbed and it has a moderate half-life in plasma. The total radioactivity in plasma following administration of [3H]equilin sulfate as part of a mixture of conjugated equine estrogens had significantly lower peak concentration (Cmax), a lower area under the curve (AUC), a longer terminal half-life (t1/2) and a longer mean residence time (MRT) than when [3H]equilin sulfate was given alone, indicating that the other components in the conjugated equine estrogen preparation altered the pharmacokinetics of equilin sulfate. An average of 26.7 +/- 4.4% of the administered radioactive dose was excreted in urine of dogs receiving [3H]equilin sulfate. Again, a significantly lower percentage (21.4 +/- 6.3%, P = 0.023) was eliminated in urine of dogs receiving [3H]equilin sulfate in the conjugated equine estrogen preparation, indicating that the absorption of equilin sulfate was perhaps altered by the other components in the conjugated equine estrogen preparation. Metabolite profiles of plasma and urine were similar. Equilin, equilenin, 17 beta-dihydroequilenin, 17 beta-dihydroequilin, 17 alpha-dihydroequilenin and 17 alpha-dihydroequilin were present in both matrices. 17 beta-Dihydroequilin and equilin were the two major chromatographic peaks in plasma samples. 17 beta-Dihydroequilenin and 17 beta-dihydroequilin were the major metabolites in urine. In conclusion, following oral administration of [3H]equilin sulfate to dogs, the radioactivity is rapidly absorbed. The disposition of equilin sulfate is altered by the other components that are present in the conjugated equine estrogen preparation Premarin. The reduction of the 17-keto group and aromatization of ring-B are the major metabolic pathways of equilin in the dog.

Animals↗
PubMed1981

Radioimmunoassay of plasma equilin and estrone in postmenopausal women after the administration of premarin.

A RIA for the measurement of plasma equilin (3-hydroxy-1,3,5-(10)7-estratetraen-17-one) and estrone in postmenopausal women and other estrogen-deficient women on exogenous equine estrogen replacement therapy is described. Antiserum against estriol-3,16,17-trihemisuccinate-HSA and high specific activity [2,4-3H]equilin and [6,7-3H]estrone were used in the assay procedure. Specificity of the assay was achieved by separation of equilin from estrone by chromatography on micro-Celite partition columns using silver nitrate as the stationary phase. The sensitivity of the standard curves for both equilin and estrone was 10-20 pg, and the smallest amount of estrone and equilin that could be measured accurately in the plasma was 250 pg/ml for both steroids. The coefficient of variation for both steroids ranged from 1-8%, over a range of 250-5000 pg/ml plasma. The interassay coefficients of variation for equilin and estrone were 4.6% and 2.4%, respectively. After the administration of 10 mg Premarin iv, maximum concentrations of 4 and 11.2 ng/ml for equilin and estrone, respectively, were obtained after 20 min. Thereafter, both steroids disappeared from the plasma gradually. When 10 mg Premarin were administered orally, equilin and estrone appeared in the blood gradually, and maximum levels of 560 and 1400 pg/ml were reached after 3 and 5 h for equilin and estrone, respectively. Equilin gradually disappeared, and by 24 h, only small amounts (125 pg/ml) were detectable. The levels of estrone declined more rapidly, though it was still detectable after 24 h. These preliminary results indicate that equilin sulfate is converted to circulating unconjugated equilin in a manner similar to the conversion of circulating estrone sulfate to estrone.

17-Ketosteroids↗
PubMed1997

Equilin, a principal component of the estrogen replacement therapy premarin, increases the growth of cortical neurons via an NMDA receptor-dependent mechanism.

Regulation of both the outgrowth and the survival of neurons involved in cognitive function can have a significant impact on the function of neural networks involved in memory and other cognitive processes. Results of this investigation demonstrated that 17beta-estradiol and the estrogenic steroids estrone, estriol, mestranol, and equilin induced significant increases in cortical nerve cell growth. Of the neurotrophic estrogenic steroids, equilin was most efficacious. We therefore conducted an extensive analysis of equilin-induced neurotrophism. Equilin induced highly significant increases in the growth of both the macro and micro features of cortical nerve cell morphology. The growth-promoting effects of equilin were present in both serum-containing and serum-free media, indicating that the growth-promoting effect of equilin is direct and not dependent upon factors present in serum. Analysis of the regional selectivity of equilin-induced neurotrophism in the cerebral cortex demonstrated that equilin significantly increased the growth of neurons from the frontal, temporal, and occipital regions, with neurons from the parietal region also influenced, though more modestly. We pursued the mechanism of equilin-induced neurotrophism and found that the growth-promoting effects of equilin were completely abolished in the presence of the glutamatergic NMDAreceptor antagonist AP5. Equilin is a major component of Premarin, the leading prescribed pharmaceutical for estrogen replacement therapy for postmenopausal women in the United States. Results of this investigation have the potential of influencing the application and design of therapeutic agents for the prevention of cognitive decline in estrogen deficient women and for the prevention of Alzheimer's disease in postmenopausal women, a group that comprises a large sector of the population, the size of which will continue to grow in the coming decades.

2-Amino-5-phosphonovalerate↗
PubMed1981

In vivo metabolism of [3H]equilin in the pregnant mare.

[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.

17-Ketosteroids↗
PubMed1982

The metabolism of equilin in normal men.

Healthy adult males received either [3H]-equilin intravenously (one subject) or a larger mass of unlabelled equilin orally (three subjects). Blood samples were taken at 20, 40, 60, 90 and 120 min and every h thereafter until eight h after injection. Urine was collected in 24 h aliquots for five days from all subjects. The half-life of the disappearance of the unconjugated radioactivity from blood was 30 min and that in the conjugated sulfate fraction was 5 1/2 h. Approximately 50% of the injected radioactivity was recovered in the urine over 5 days. After extraction, hydrolysis and fractionation, most (83%) of the radioactive material found in the urine was present in the glucuronide fraction while only 2 and 6% were present in the unconjugated and sulfate fractions, respectively. The three fractions were combined for further isolation and identification of the metabolites. Radiochemically pure equilin, equilenin, 17 beta-dihydro-equilin and 17 beta-dihydroequilenin were isolated and identified but the largest fraction of radioactivity (70.5%) was present in the form of metabolites which are more polar than any of the known ring B unsaturated estrogens. These appear to be polyhydroxy 17-reduced ring B unsaturated estrogens. These results indicate that the ring B unsaturated estrogen equilin is being metabolized in man in a somewhat similar manner to that of the classical estrogen estrone. Knowledge of the formation of 17 beta-dihydroequilin from equilin in man is of importance because this estrogen is approximately 8 times more potent as a uterotrophic agent than the commonly used estrogen, equilin.

17-Ketosteroids↗
PubMedDate not supplied

Immunoaffinity extraction for liquid chromatographic determination of equilin and its metabolites in plasma.

Immunoaffinity extraction for the high-performance liquid chromatographic determination of equilin and its metabolites in plasma has been achieved. The antibody raised against an equilin 3-O-carboxymethyl ether-bovine serum albumin conjugate was characterized as having a high affinity for equilin and equilenin. One mL of the immunoaffinity adsorbent prepared by immobilization of an antibody was capable of retaining up to 1 microgram of equilin and equilenin, to 100 ng of other metabolites including 2-methoxylated and 17 beta-reduced compounds, and to 0.3 micrograms of glucuronic acid conjugates at C-3. The adsorbates were recovered qualitatively by elution with 90% aqueous (v/v) methanol without any interfering peaks on the chromatogram.

Chromatography, Affinity↗
PubMed1980

Serum equilin, oestrone, and oestradiol levels in postmenopausal women receiving conjugated equine oestrogens ('Premarin').

Two groups of postmenopausal women were seen at monthly intervals during a 6-month trial of cyclic therapy with conjugated equine oestrogens ('Premarin'). the seven women in the first group were taking premarin alone and the six women in the second group were taking premarin plus a progestagen, norethisterone acetate. On each visit, serum unconjugated oestrogens were measured by radioimmunoassay. Mean concentrations for the first group were 393 (+/- 203, SD) pmol/l for 17 beta-oestradiol, 599 (+/- 180) pmol/l for oestrone, and 6840 (+/- 5130) pmol/l for equilin. Corresponding levels for the second group were 342 (+/- 112) pmol/l, 564 (+/- 279) pmol/l, and 8840 (+/- 4020) pmol/l. 3 months after completion of therapy, the oestrone and 17 beta-oestradiol concentrations had returned to pre-treatment levels in both groups, but equilin was detected in 3 out of 3 women in the first group at a mean level of 532 (+/- 267) pmol/l and in 2 out of 4 women in the second group at 1170 (+/- 870) pmol/l. In view of the prolonged presence of equilin and the possible association between treatment with conjugated equine oestrogens and endometrial cancer, it is suggested that equilin-containing compounds should not be given for more than 12 months.

17-Ketosteroids↗
PubMed1999

The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone.

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. In this study, we have compared the chemistry of the major catechol metabolite of equilin (4-hydroxyequilin), which is found in several estrogen replacement formulations, to the equilenin catechol (4-hydroxyequilenin). Unlike endogenous catechol estrogens, both equilin and equilenin were primarily converted by rat liver microsomes to 4-hydroxylated rather than 2-hydroxylated o-quinone GSH conjugates. With equilin, a small amount of 2-hydroxyequilin GSH quinoids were detected (4-hydroxyequilin:2-hydroxyequilin ratio of 6:1); however, no peaks corresponding to 2-hydroxyequilenin were observed in incubations with equilenin. These data suggest that unsaturation in the B ring alters the regiochemistry of P450-catalyzed hydroxylation from primarily 2-hydroxylation for endogenous estrogens to 4-hydroxylation for equine estrogens. 4-Hydroxyequilenin-o-quinone reacts with GSH to give two mono-GSH conjugates and one di-adduct. The behavior of 4-hydroxyequilin was found to be more complex than 4-hydroxyequilenin as conjugates resulting from 4-hydroxyequilenin were detected in addition to the 4-hydroxyequilin-GSH adducts. The mechanism of decomposition of 4-hydroxyequilin likely involves isomerization to a quinone methide which readily aromatizes to 4-hydroxyequilenin followed by autoxidation to 4-hydroxyequilenin-o-quinone. Similar results were obtained with 2-hydroxyequilin, although, in contrast to 4-hydroxyequilenin, 2-hydroxyequilenin does not autoxidize and the reaction stops at the catechol. Since 4-hydroxyequilin is converted to 4-hydroxyequilenin and 4-hydroxyequilenin-o-quinone, similar effects were observed for this equine catechol, including consumption of NAD(P)H likely by the 4-hydroxyequilenin-o-quinone, depletion of molecular oxygen by 4-hydroxyequilenin or its semiquinone radical, and alkylation of deoxynucleosides and DNA by 4-hydroxyequilenin quinoids. Finally, preliminary studies conducted with the human breast tumor cell line MCF-7 demonstrated that the cytotoxic effects of the catechol estrogens from estrone, equilin, and 2-hydroxyequilenin were similar, whereas 4-hydroxyequilenin was a much more potent cytotoxin ( approximately 30-fold). These results suggest that the catechol metabolites of equine estrogens have the ability to cause alkylation/redox damage in vivo primarily through formation of 4-hydroxyequilenin quinoids.

Animals↗
PubMed1999

Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+.

Excess 17beta-estradiol (E2), the most potent of human estrogens, is known to act as a stimulus for the growth of breast tumors. Human estrogenic 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction of inactive estrone (E1) to the active 17beta-estradiol in breast tissues, is a key enzyme responsible for elevated levels of E2 in breast tumor tissues. We present here the structure of the ternary complex of 17beta-HSD1 with the cofactor NADP+ and 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin), an equine estrogen used in estrogen replacement therapy. The ternary complex has been crystallized with a homodimer, the active form of the enzyme, in the asymmetric unit. Structural and kinetic data presented here show that the 17beta-HSD1-catalyzed reduction of E1 to E2 in vitro is specifically inhibited by equilin. The crystal structure determined at 3.0-A resolution reveals that the equilin molecule is bound at the active site in a mode similar to the binding of substrate. The orientation of the 17-keto group with respect to the nicotinamide ring of NADP+ and catalytic residues Tyr-155 and Ser-142 is different from that of E2 in the 17beta-HSD1-E2 complex. The ligand and substrate-entry loop densities are well defined in one subunit. The substrate-entry loop adopts a closed conformation in this subunit. The result demonstrates that binding of equilin at the active site of 17beta-HSD1 is the basis for inhibition of E1-to-E2 reduction by this equine estrogen in vitro. One possible outcome of estrogen replacement therapy in vivo could be reduction of E2 levels in breast tissues and hence the reduced risk of estrogen-dependent breast cancer.

Amino Acid Sequence↗
PubMed1975

Oestrone and equilin in the plasma of the pregnant mare.

A method for the extraction of oestrone and equilin from the plasma of the pregnant mare is described, and the levels obtained for eighty-two samples from fourteen Welsh Mountain Ponies at different stages of pregnancy are recorded. Oestrone (fifteen samples) and equilin (three samples) were not found before Day 120. From Day 120 to 240, oestrone levels exceeded 100 ng/ml and then declined to parturition. The high concentrations of oestrone in mid-pregnancy were associated with gradually increasing concentrations of equilin which tended to plateau after Day 180 at just under 100 ng/ml and declined significantly only in the last month of pregnancy. Evidence is presented that both oestrone and equilin occur in peripheral plasma largely as sulphates.

17-Ketosteroids↗
PubMed1975

[Equilin sulphate in the treatment of the menopausal syndrome (author's transl)].

0.25 sodium equilin sulphate and 0.625 mg Premarin were compared as to their effects in 12 postmenopausal syndrome. The initial daily dosage of 0.25 mg equilin had a stronger oestrongenic effect in the alleviation of vasomotor disturbances than subsequently-administered Premarin. No significant difference was found in effect on the vaginal epithelium or the endometrium or in the incidence of irregular bleeding. The number of women in whom withdrawal bleeding was reported was considerably reduced by lowering the dosage to 0.2 mg equilin sulphate. Consequently 0.2 to 0.3 mg equilin sulphate must be considered the optimum dosage.

17-Ketosteroids↗
PubMed2000

HPLC-fluorescence determination of equilin and equilenin in postmenopausal women's urine.

A high-performance liquid chromatographic (HPLC) method with fluorescence detection (lambda(ex) = 280 nm; lambda(em) = 410 and 312 nm) in combination with a post-column on-line photochemical derivatization is described for the determination of equilin and equilenin in urine from normal postmenopausal women after therapy with conjugated oestrogens. The column effluents were subjected on-line to UV irradiation (254 nm) and the photo-induced modifications were useful for the identification of the analytes. The conjugated (sulphate and glucuronide) forms were analysed after enzymatic or chemical hydrolysis and extracted with chloroform. Solid-phase extraction using strong anion-exchange sorbent was applied to the analysis of unconjugated oestrogen fraction to obtain a practical and reliable sample clean-up. The HPLC separations were achieved using ODS columns with a mobile phase consisting of 0.05 M triethylamine phosphate buffer (pH 4.0)-acetonitrile (64:36, v/v) at a flow rate of 1.0 mL/min. The method was accurate and reproducible; for the equilin and equilenin separation isocratic conditions were satisfactory, allowing a sensitive detection in urine samples with a detection limit of about 50 fmol for equilin (lambda(ex) = 280 nm; lambda(em) = 312 nm, after photoderivatization) and 10 fmol for equilenin (lambda(ex) = 280 nm; lambda(em) = 410 nm).

Chromatography, High Pressure Liquid↗
PubMed1987

Equilin and equilenin biosynthesis. Stereochemistry of aromatization of 3-hydroxy-3,5,7-androstatrien-17-one by horse placenta.

The metabolic pathway leading to equilin and equilenin biosynthesis in the pregnant mare is different from that of estrone and estradiol and it is apparently cholesterol-independent. The precise precursors and intermediates and the stereomechanism of equine placental aromatization have not been established. [1,2-3H, 4-14C]3-Hydroxy-3,5,7-androstatrien-17-one was synthesized as a potential substrate and the 3H-distribution was analyzed by biochemical and chemical derivatization methods. The substrate was converted to equilin, equilenin and Heard's ketone by horse placental microsomes with a sp. act. of 74, 18 and 2.8 pmol/h/mg, respectively, and only to equilin by human placental microsomes with a rate of 26 pmol/h/mg. Analysis of the loss of 3H-labeling during aromatization showed the stereospecific 17 beta,2 beta-cis hydrogen elimination for equine estrogen biosynthesis both by horse and human placental microsomes. This is the same as for estrone and estradiol biosynthesis by both placentas. The biosynthesis of Heard's ketone, a non-phenolic ring-B aromatic C18 steroid, by horse placental microsomes was found to involve none of the four hydrogens at C-1 and C-2. This refutes the previous postulate that Heard's ketone arises from equilenin by reduction of the ring-A.

17-Ketosteroids↗
PubMed1991

Metabolism of [3H]equilin in normal and malignant human endometrium and in endometrial adenocarcinoma transplanted into nude mice.

One of the main components of conjugated equine estrogens is equilin sulfate and this estrogen in postmenopausal women is metabolized to 17 beta-dihydroequilin, 17 beta-dihydroequilenin and equilenin. To investigate the possibility that some of these estrogens may be formed directly in the target tissues, we studied the in vitro metabolism of [3H]equilin in various types of normal and malignant human endometrium, including adenocarcinoma grown in athymic nude mice. The results indicate that normal and neoplastic human endometrium can form the above three metabolites. The highest level of 17 beta-reduced products were isolated from the normal secretory endometrium. Equilenin was the most abundant metabolite isolated from both the normal and malignant endometrium. The formation of [3H]equilenin indicates the presence of a 6,8(9) steroid dehydrogenase-isomerase in the human endometrium. The formation of 17 beta-dihydroequilin in the endometrium may be of importance as this estrogen is 8 times more potent as a uterotrophic agent than equilin and estrone.

Adenocarcinoma↗