Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Estrone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

Behavioral characteristics of freemartins administered estradiol, estrone, testosterone, and dihydrotestosterone.

Eighteen genetic females born co-twin with males and diagnosed as being sterile intersexes (freemartins) were studied from birth to 79 weeks of age. Testosterone (T) and estrone (EI) were administered in Silastic capsules of two groups from birth to 50 weeks of age and other animals were left untreated. At 50 weeks the two treated groups had larger implants installed and the untreated animals were assigned to a new estrone (EII) and estradiol (E2) treatment. Later a dihydrotestosterone (DHT) group was formed in comparison with new E2 and testosterone propionate-enanthate (TP-TE) groups, plus untreated controls. Vulvar interest, Flehmen lip curl, mounting, and agonistic behavior were recorded daily for 30 min while animals were allowed social interaction. Agonistic behavior, interest in the genital area, and mounting were induced or stimulated by T, TP-TE, and E2, but not by DHT or estrone (EI or EII). Also, only animals in the T, TP-TE, and E2 groups induced to mount displayed the standing type of behavioral estrus. Flehmen lip curl was stimulated only by T or TP-TE. The evidence is interpreted to indicate that T, per se, evokes the lip curl, but it probably stimulates other responses at the neural level by conversion to E2. Also, the freemartin response, the response of castrates to steroid hormones, and current knowledge of circulating steroid hormones in male and female cattle could be interpreted to indicate that the neural tissue responsible for sexual behavior in both sexes of this species may respond similarly in several respects.

Agonistic Behavior↗

The affinity alkylators, 11 alpha-bromoacetoxyprogesterone and estrone 3-bromoacetate, modify a common histidyl residue in the active site of human placental 17 beta,20 alpha-hydroxysteroid dehydrogenase.

Purified human placental 17 beta,20 alpha-hydroxysteroid dehydrogenase (native enzyme) was completely inactivated by the affinity alkylator, estrone 3-bromoacetate, in the presence of cofactor (NADPH). The inactivated enzyme was reactivated to 100% activity by base-catalyzed hydrolysis of the steroidal ester-enzyme conjugate and then repurified by dialysis. Control enzyme in mixtures which contained estrone in place of alkylator was treated the same as the reactivated enzyme. 11 alpha-Bromo[2'-14C]acetoxyprogesterone, an active site-directed affinity alkylator of the enzyme, produced 5.0-fold less radiolabeled 3-(carboxymethyl)histidine and S-(carboxymethyl)cysteine plus 1.4-fold more 1,3-bis(carboxymethyl)-histidine in the reactivated enzyme than in the control enzyme. The lesser amount of S-(carboxymethyl)cysteine and greater amount of 1,3-bis(carboxymethyl)histidine resulted from nonspecific interactions between the reactivated enzyme and the progestin radioalkylator. The nonradiolabeled 3-(carboxymethyl)histidine originally produced by estrone 3-bromoacetate in the enzyme active site hindered radioalkylation of this amino acid by 11 alpha-bromo[2'-14C]acetoxyprogesterone to yield 5-fold less radiolabeled 3-(carboxymethyl)histidine in the reactivated enzyme relative to control enzyme. Thus, the estrogen and progestin affinity alkylators modified a common histidyl residue in the active site. These studies are direct evidence that the estradiol 17 beta-dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities reside at a common locus on a single protein.

Alkylation↗

Use of a monoclonal antibody to estrone-3-glucuronide in an enzyme-linked immunosorbent assay (ELISA).

A direct urinary ELISA for estrone-3-glucuronide has been produced following cloning and characterisation of a monoclonal antibody to the above estrogen metabolite. The ELISA follows our established pattern of absorbing a thyroglobulin conjugate, to which estrone-3-glucuronide has been coupled, to the wells of a microtitre plate using guanidine hydrochloride. A competition reaction between either standards/samples and the adsorbed hormone compete for antibody combining sites. The assay is completed by addition of an anti-mouse Ig-peroxidase complex and read at 492 nm following additions of O-phenylenediamine substrate in under 4 h. The correlation between urinary "total estradiol" and "total estrone and estradiol" is very good and, in conjunction with our ELISA for pregnanediol glucuronide, has allowed for the improved clinical management of infertile and subfertile women.

Animals↗

Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men.

The feminization frequently observed in men with alcoholic liver disease has not been satisfactorily explained by existing reports. We have measured plasma estrone, prolactin, estrogen-stimulated neuorphysin, and sex steroid-binding globulin concentrations in 50 men with chronic alcoholism and varying degrees of alcoholic liver disease in an effort to further elucidate possible hormonal mechanisms responsible for the observed feminization. Plasma concentrations of each of these parameters were at least two-fold elevated (p smaller than or equal to 0.01) when compared to values obtained for the same steroid or protein in plasma obtained from normal men. The plasma concentrations of estrone and prolactin in men studied with synecomastia were significantly greater (p smaller than or equal to 0.01 and p smaller than or equal to 0.05, respectively) than were the concentrations of these two hormones in those without this physical sign. Similarly, those men with spider angiomata had significantly greater (p smaller than or equal to 0.01) plasma estrone levels than did the men without this cutaneous vascular abnormality. These significant hormone elevations may contribute to the pathogenesis of feminization so frequently observed in chronic alcoholic men.

Adult↗

Identifications of radioactive steroid estrogen conjugates in blood plasma of laying hens after intramuscular injection of (4--14C)-estrone.

[4--14C] Estrone was injected intramuscularly into six laying hens. Fifty minutes later the hens were exsanguinated. The plasmas were examined for conjugates of radioactive phenolic steroids by recovery on columns of Amberlite XAD-2 or by extraction with tetrahydrofuran followed by chromatography on a column of DEAE-Sephadex A-25 in a gradient of NaCl. The biggest Sephadex chromatographic fraction (50,4% of total) contained about 42% of its radioactivity as estradiol-17alpha-3-sulfate and 18% as estradiol-17beta-3-sulfate and the remaining 40% was identified tentatively as estradiol-17alpha-17-sulfate plus a small proportion of estradiol-17beta-17-sulfate. The second biggest Sephadex chromatographic fraction (12.7% of total) was a mixture of conjugates not further identified. Minor fractions identified comprised estrone-beta-glucuronide (2.8%), estradiol-17alpha-3-beta-glucuronide (2.8%), estradiol-17beta-3-beta-glucuronide (2.3%) and estrone sulfate (6.0%). Evidence was obtained for the presence of small proportions of estradiol-17alpha disulfate and estradiol-17beta disulfate.

Animals↗

Identification of some plasma metabolites of 6, 7-3-H-estrone glucosiduronate in male dogs.

Following the constant infusion of 6, 7-3-H-estrone glucosiduronate in male dogs for a period of 120 minutes, the radioactive metabolites present in the plasma were separated by solvent partition, DEAE-Sephapadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and steroids and their derivatives. Most of the radioactivity in the plasma was identified as estrone glucosiduronate. The major metabolite present was estradiol-17-beta-3-glucosiduronate. Small amounts of estradiol-17-alpha-3-glucosiduronate and free estrone were also identified. Three other minor conjugates were separated, but positive identification could not be made.

Animals↗

The transfer of estrone glucuronide to bile in an isolated perfused rat liver system.

An isolated rat liver perfusion system has been utilized in a study of the biliary excretion of estrone glucuronide. The estrogen was initially shown to be excreted without prior metabolism. Disappearance from the medium was rapid and biliary concentrations exceeded that in the medium by more than a thousand-fold. Disappearance rates were decreased when medium estrone glucuronide concentrations exceeded 0.29 mM. Inhibition by other steroidal conjugates, testosterone glucuronide, 2-methoxyestrone (3-hydroxy-2-methoxy-estra-1,3,5(10)-trien-17-one glucuronide and 2-hydroxyestrone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) glutathione, was also demonstrated. Phenolphthalein glucuronide, at 10 times the molar concentration of estrone glucuronide, did not affect the medium clearance of the latter compound. These findings indicate the possibility of utilizing this system for further studies of possible interactions by other organic compounds for excretion via the biliary route.

Animals↗

Steroid estrogen conjugates in hens' urine II. Identifications of some minor conversion products of intramuscularly injected [4(-14C)]estrone.

[4(-14C)]Estrone was injected intramuscularly into two mature laying Rhode Island Red hens. Radioactive steroids and steroid conjugates recovered from the urine on Amberlite XAD-2 columns were fractionated on columns (100 cm) of DEAE-Sephadex A-25 by NaC1 gradients. The presence of the following were confirmed, the figures in brackets indicating average proportions as per cent of total radioactivity recovered after Sephadex column chromatography:-the 3-beta-glucuronides of estrone (10.9) and of estradiol-17alpha plus estradiol-17beta(9.8): the 17-beta-glucuronides of estradiol-17alpha plus estradiol-17beta (2.1); the 3-sulfates of estrone (14.5) and of estradiol-17alpha plus estradiol-17beta(27.4); and the disulfates of estradiol-17alpha plus estradiol-17beta (2.3). The following additional conjugates were identified:-a beta-glucuronide of 16-epiestriol (0.2) and a beta-glucuronide of 16-keto-estradiol-17beta (0.2); the 3-sulfates of 16-epiestriol (1.4), of 17-epiestriol (0.9), of 16,17-epiestriol (0.7), of 16-keto-estradiol-17beta (1.1), and of 2-methoxyestrone (0.7). Some evidence was obtained for the presence of 16,17-epoxy-estratrienol-3-sulfate (1.9).

Animals↗

Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.

The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.

Adult↗

Identification of 6 alpha- and 7 alpha-hydroxyestrone as major metabolites of estrone and estradiol in porcine uterus.

Polar metabolites extracted from the effluents of viable porcine uterine strips superfused with either 6,7-3H-estrone or 6,7-3H-estradiol were identified as a 1:1 mixture of 6 alpha-hydroxyestrone and 7 alpha-hydroxyestrone by paper chromatography in various systems, derivatization and crystallizations to a constant specific activity. The hydroxylated compounds are the only derivatives detected after estrone superfusion. The major metabolite of estradiol released in short-time experiments is estrone followed by its 6 alpha- and 7 alpha-hydroxylated derivatives.

Animals↗

Estrone sulfatase activity in human uterine leiomyoma.

Human uterine leiomyoma is a benign tumor and its development is closely related to estrogen. In this study, estrone sulfatase (E1SF) activity and concentrations of estrone (E1) and estrone sulfate (E1S) were measured in endometrial, leiomyoma, and myometrial tissues of the same human uterus (n = 11) with a leiomyoma. E1SF activity in endometrial tissue overlying a leiomyoma was 2.62 +/- 0.29 nmole/hr/mg protein (mean +/- SD), this activity being significantly higher (P less than 0.01) compared with that in normal endometrial tissue (2.0 +/- 0.24 nmole/hr/mg protein). E1SF activity in normal endometrial tissue was significantly higher (P less than 0.001) compared with that in leiomyoma tissue (0.49 +/- 0.82 nmole/hr/mg protein) or myometrial tissue (0.76 +/- 0.10 nmole/hr/mg protein). We also found a significant difference (P less than 0.05) in E1SF activity between leiomyoma tissue and myometrial tissue. On the other hand, the E1 concentration in endometrial tissue overlying a leiomyoma (10.9 +/- 8.9 pg/mg protein) proved to be higher than that in endometrial tissue overlying normal myometrium (1.23 +/- 1.97 pg/mg protein). E1S concentrations in these tissues, however, were 631 +/- 339 and 902 +/- 482 pg/mg protein, respectively, these values showing a trend opposite that of the E1 concentration data. Thus, these results suggest that high E1SF activity and high E1 concentration in the endometrium overlying a leiomyoma may be related to estrogen supply to a uterine leiomyoma node.

Endometrium↗

Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue.

Specific activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 48 tissue specimens of human female breast cancer and, in addition, 48 nonmalignant tissue specimens obtained in each case from the same cancer-bearing breast. In all cases the nonmalignant tissue showed greater conversion of estradiol-17 beta into estrone than the neoplastic tissues. In normal human breast tissue of premenopausal women specific enzyme activity depended on the phase of the MENSTRUAL CYCLE: the highest values of 17 beta-HSD activity were found in the early secretory phase. To determine the intracellular distribution of the 17 beta-HSD, purified microsomes, mitochondria, peroxysomes, lysosomes, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the 17 beta-HSD was mainly located in mitochondria and microsomes. Furthermore it could be demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17 beta-HSD was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements and maximal velocities) of a cytoplasmic, nuclear, mitochondrial and microsomal 17 beta-HSD of normal and neoplastic human mammary tissue were compared. Maximal velocity was highest in enzyme preparations of normal mammary tissue obtained from premenopausal women in the early secretory phase. Km-values wrere nearly identical in normal and neoplastic mammary tissue preparations (approx. 1 X 10(-6) M). NAD was more efficient than NADP as a cofactor. For the conversion of estradiol to estrone the optimum temperature was approximately 40 degrees C and the optimum pH 9.5. For the reduction of estrone the optimum pH was 6.5. Sulphydryl groups were shown to be essential for catalysis.

Breast↗

Use of ion-exchange and hydrophobic-interaction chromatography for the rapid purification of lysozyme-estrone glucuronide conjugates.

Estrone glucuronide conjugates of hen egg white lysozyme were prepared by both the mixed-anhydride and active-ester coupling procedures. Both methods gave good yields of conjugate but the active-ester procedure gave a more diverse range of products consistent with a greater acylating ability. Unreacted lysozyme which was present in all cases was removed by a combination of cation-exchange chromatography on a Pharmacia Mono-S column and hydrophobic-interaction chromatography on an Alkyl Superose column. The conjugate families were more hydrophobic than native lysozyme. The chromatographic behaviour of the reaction mixtures on Mono S columns under non-denaturing conditions was complex as a result of hydrophobic effects and only at pH values above 7.0 did the conjugates elute in the order of their overall charges. At pH values below 6.0 the conjugates, although less charged than lysozyme, eluted last on salt gradients. In contrast when denaturing 7 M urea buffers were used the conjugates eluted in the order of their electrostatic charges and reproducible patterns were obtained which served as an excellent analytical system for lysozyme-steroid glucuronide conjugates. The purified conjugate material from the active-ester reaction gave over 90% inhibition of the lytic activity in the presence of an estrone glucuronide antibody. When used in a homogeneous enzyme immunoassay system the levels of urinary estrone glucuronide encountered in a normal menstrual cycle were easily measured.

Chemical Phenomena↗

Effect of bovine growth hormone gene expression, sex and age on plasma gonadotropins, estrone and testosterone in prepuberal pigs.

Chronic supraphysiological blood levels of growth hormone (GH) may retard sexual maturation in swine. Pigs used in this study included four founder transgenic pigs (two gilts and two boars) expressing a mouse transferrin (TF) promoter fused to a bovine (b) GH structural gene, 13 second- or third- generation transgenic pigs (seven gilts and six boars) expressing a mouse metallothionein (MT) promoter fused to a bGH structural gene and 16 control littermates (eight gilts and eight boars). Blood plasma levels of LH, FSH, estrone and testosterone were measured to determine whether expression of bGH genes altered secretion of hormones between 80 and 180 days of age. Presence of a bGH gene was detected by hybridization of DNA in dot blots of tail biopsies. Expression of a bGH gene was detected by radioimmunoassay of plasma bGH. In four TFbGH founder transgenic pigs bGH ranged from 164 to 1948 ng/ml; in one MTbGH transgenic boar of line 3104 bGH was 1211 ng/ml; and in 12 pigs of line 3706 bGH ranged from 25 to 190 ng/ml. Expression of bGH in transgenic pigs lowered (P = .0192) plasma LH with no significant differences between sexes, had no significant effect on plasma FSH and lowered plasma estrone (P = .0001) and testosterone (P = .0269) in boars (but not gilts). Plasma estrone and testosterone were higher (P = .0001) in boars than in gilts. Plasma FSH was higher (P = .0001) in gilts than boars and decreased (P = .0001) with advancing age in gilts but not in boars.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Inhibition of human placental sterylsulfatase by synthetic analogs of estrone sulfate.

Synthetic analogs of estrone sulfate which carry differently substituted sulfonyl groups at position 3 of an invariable 3-desoxyestrone (dE1) moiety were tested in vitro as inhibitors of the human placental sterylsulfatase. Using both placental microsomes and a highly purified placental sterylsulfatase preparation as the enzyme source and dehydroepiandrosterone [35S]sulfate or estrone [35S]sulfate as the substrate, the following order of inhibitory potencies was observed: dE1-3-sulfonylchloride > dE1-3-sulfonylfluoride approximately dE1-3-sulfonate > dE1-3-sulfonamide approximately 3-methylsulfonyl-dE1. According to the results, the association of enzyme and inhibitor appears to be favored by an electronegative substituent at the sulfur atom (-C1, -F, -O-). Since, however, even the most potent synthetic inhibitor was bound by the enzyme with significantly lower affinity than was the natural substrate estrone sulfate, an oxygen function between the aromatic ring and the sulfur atom may be necessary for high affinity binding towards the sterylsulfatase. In addition to its fast reversible association with the enzyme, dE1-3-sulfonylchloride further affected the sulfatase activity in a time-dependent manner. This latter inhibitory activity which may be due to a covalent modification (alkylation) of sterylsulfatase by the analog was partially prevented in the presence of substrate.

Arylsulfatases↗

Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase.

A series of estrone conjugates of the type estrone-3-O-C(O,S)-X have been prepared and evaluated for inhibition of human steroid sulfatase (STS). Among the carbamate (6), thiocarbamate (8), cyanate (7), formate (9), and acetate (10) analogs of estrone, only 9 was found to inhibit STS in a time- and concentration-dependent manner. With an IC(50) of 0.42 microM 9 is the first potent inactivator of STS which does not feature the sulfamate group. Furthermore a formate-type inhibitor featuring a benzoxazole moiety in place of the steroid skeleton (14) was prepared, suggesting a general principle of inactivation by the formate group. As the mode of action we propose an immediate transfer of the formyl moiety to a nucleophilic residue in the active site of STS.

Binding Sites↗

Bone density effects of continuous estrone sulfate and varying doses of medroxyprogesterone acetate. Ogen/Provera Study Group.

OBJECTIVE: To establish the optimum oral daily dose of medroxyprogesterone acetate with estrone sulfate for 2 years to maintain bone density. METHODS: A multicenter, double-blind study involved 568 postmenopausal women given estrone sulfate, 1.25 mg, and randomized to receive 2.5, 5, or 10 mg of medroxyprogesterone acetate. Bone density analyses of the lumbar spine and femoral neck were done at baseline and 12 and 24 months. RESULTS: There was a significant increase from baseline to 24 months in mean lumbar spine (4.0% +/- 0.27%) and femoral neck (3.2% +/- 0.28%) bone density, with no significant differences between the treatment groups. Factors most influencing bone density changes were baseline bone density and treatment duration. Significant increases were seen in the spine over 2 years; in the hip, those occurred in the first 12 months only. In both sites, lower baseline bone density resulted in greater increases. In the spine only, no previous hormone replacement therapy, higher body mass index, more than 2 years postmenopause, and nonsmoking resulted in greater gains. Once those covariates and center-to-center variations were corrected for, in the spine, the 10-mg group had smaller increases than the other groups. Changes were unrelated to age, parity, calcium, and alcohol intakes in either site. CONCLUSION: Daily estrone sulfate, 1.25 mg, with 2.5, 5, or 10 mg medroxyprogesterone acetate was effective for preventing bone loss in postmenopausal women.

Adult↗

Direct evidence for the involvement of prostaglandin F2 alpha in the first step of estrone-induced blastocyst implantation in the spayed rat.

The effect of prostaglandin F2 alpha (PGF2 alpha) on blastocyst implantation in spayed rats has been studied. In preliminary experiments, the first implantation sites were observed 8 - 12 hours after a single injection of estrone in ovariectomized and progesterone-conditioned rats. Intraluminal instillation of PGF2 alpha into the right uterine horn 8 - 10 h after the estrone injection increased the number of implantation sites. Even treatment with PGF2 alpha without previous estrone injection induced the first step of blastocyst implantation as shown by uterine dye site reaction (Niagara-blue test). The results are discussed with regard to the possible role of PGF2 alpha in the regulation of the blastocyst implantation processes in the rat.

Animals↗