Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crude subcellular fractions from rat uterus contain a HCO-3 -stimulated Mg2+ -ATPase with properties analogous to those previously reported for the enzyme in gastric mucosa, pancreas, salivary gland and liver lyosome. Estradiol-17 beta treatment of ovariectomized rats resulted in an increase in uterine mitochondrial (HCO-3 +Mg2+)-ATPase and Mg2+ -ATPase activity. In an early response (105 min) to estradiol-17 beta treatment of ovariectomized rats, the lysosomal enzyme, beta-N-acetylglucosaminidase increased in the nuclear and mitochondrial fractions and decreased in the microsomal and supernatant fractions.
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PMID:Properties of a bicarbonate-stimulated ATPase from rat uterus. 13 20

17 beta-Hydroxysteroid dehydrogenase activity towards estradiol-17 beta has been demonstrated in the 105,000 x g supernatant of rabbit uterus. Hydroxylapatite chromatography of the enzyme activity isolated by ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography yielded a single 17 beta-hydroxysteroid dehydrogenase activity. Further purification of the enzyme preparation by isoelectric focusing resulted in multiple peaks of activity. The molecular weight of the enzyme, caculated from mobility data on Sephadex gel, is approximately 64,000. Some properties of partially purified 17 beta-hydroxysteroid dehydrogenase activity have been studied. Estradiol-17 beta reacts at a faster rate than testosterone. The Km for estradiol is 4.16 x 10(-5) mol/l for the NAD-linked enzyme activity and 4.37 x 10(-5) mol/l when NADP as cofactor was used. The ratio of the maximal velocity for NADP to that for NAD was 1.42. The pH-optimum for estradiol appears between 9.5 and 10.5 and for estrone between 5.5 and 6.5. The enzyme appears to be of the sulfhydryl type.
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PMID:Purification and properties of the soluble 17 beta-hydroxysteroid dehydrogenase of rabbit uterus. 16 Jun 96

Estradiol is a natural estrogen which favors cellular hyperplasia at the level of its target organs. As for progesterone, its activity may be synergic or antagonist of estradiol. In the first case, progesterone has generally a secretory activity upon the target cells "prepared" by estrogens, in particular the cells of the female genital tract (uterus, breast). In the second case, progesterone may be an antiestrogen not only at the level of genital cells but also at the level of other receptors such as vascular system, etc. If an unbalance occurs in the quantitative and chronological ratio between estradiol and progesterone production (which determines the number of target cells and their secretory activity), a cellular dysplasia may be observed. This unbalance is generally characterized by an insufficiency in progesterone secretion which may be physiological (puberty, menopause) or pathological. Such a progesterone insufficiency may play a role in the pathogenesis of genital cancers (endometrial and possibly mammary). Experimental data which give some support to such an hypothesis are reported. They emphasize the importance of treatment of the progesterone insufficiency of the premenopausal period in women with the aim of preventing cellular dysplasia of the female genital tract.
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PMID:[Is progesterone insufficiency carcihogenic?]. 16 65

This is a review of estrogen receptors, largely taken from the authors' works, including estrogen receptors in the rat estrous cycle, in response to exogenous estrogens, endogenous estrogens, early responses, and the action of antiestrogens. Their method of measuring nuclear estrogen-receptor complexes entails incubating nuclear fractions with labeled estradiol, and with labeled estradiol in an excess of diethylstilbestrol, and quantitating the difference. Specific nuclear binding was documented in uterus, vagina, and pituitary of rats, in response to estradiol, diethylstilbestrol, estrone, and estriol, with a maximum of binding sites in proestrus, and the peak of estrogen secretion. The amount of estradiol bound increased with estradiol dose, but the rate of disappearance of bound nuclear estrogens was also more rapid with estrogen dose. Estradiol and estriol exhibited equal influences on early events such as RNA synthesis, but estriol did not maintain nuclear estrogen complex after 3 hours, nor permanent increase in uterine dry weight. These data lead the authors to suggest that a certain level of nuclear-receptor must be retained for at least 6 hours, as opposed to the theory that pivotal events like increased uterine blood flow, fluid imbibition, glucose transport, histamine release, and synthesis of the IP protein, is all that is required for uterine growth. Using the estrogen antagonists nafoxidine (Upjohn, 11,100 A), Cl-628, and clomiphene, and the charcoaldextran assay of total cytoplasmic estrogen-receptor binding, it was shown that the antagonists do stimulate nuclear binding, for up to 19 days in rats, but inhibit synthesis or replenishment of cytoplasmic receptors. Thus, the often observed fact that these estrogen antagonists are not antagonistic at 24 hours, but do antagonize estradiol later, is explained by prolonged retention of nuclear receptors.
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PMID:Estrogen-receptor binding: relationship to estrogen-induced responses. 17 88

Norethindrone (ENT), which is a representative in estrane series of progestogen, is not only strongly progestational but also estrogenic and in some cases, antiestrogenic. To understand progestational effect and antiestrogenic effect, the interactions of ENT on estrogen and progestogen receptors were studied in the uterine cytosol of white female rabbit. The 274,200 X G supernatant of uterine homogenate was used as cytosol. 3H-Estradiol, 3H-Progesterone, 3H-ENT or cold ENT were incubated with uterine cytosol at 4 degrees C for 2 hours. Results are as follows: 1. Sucrose gradient centrifugation [5 approximately 20% linear and 40,000 rpm (159,200 X G) for 16 hours at 4 degrees C]: ENT was bound to extrogen 8S receptor in immature rabbit uterus (Fig. 2 & 3), and to progestogen 8S receptor in estrogen primed rabbit uterus (Fig. 5). 2. Kinetic study, determined by dextran coated charcoal (0.001% dextran and 0.1% charcoal): (1) In the uterine cytosol of immature rabbit, 3H-estradiol-receptor binding was observed with Kd divide by 3.6 X 10-9 M and it was revealed that ENT was a competitive inhibitor to this binding with Ki divide by 2.6 X 10-6 M, as in Fig. 6. (2) 8S component, obtained by centrifugation of uterine cytosol (Fig. 1) in estrogen primed rabbit, binds 3H-progesterone with Kd divide by 8.1 X 10-10 M and Bm (maximal binding sites) divide by 5.0 X 10-8 M/mg of protein, and ENT was a competitive inhibitor in this binding with Ki divide by 2.3 X 10-9 M (FIG. 7 & 8). 3H-ENT-8S binding was demonstrated with Kd divide by 1.1 X 10-9 M and Bm divide by 8.7 X 10-8 M/mg of cytosol protein (Fig. 8). These results indicate: (a) ENT is bound to both estrogen and progestogen receptors in 8S macromolecules of uterine cytosol, (b) competitive inhibition of ENT to these bindings indicated that ENT is bound to these receptors at the steroid binding sites where estradiol and progesterone bind to, (c) ENT has much more affinity to progestogen receptor (Ki divide by 2.3 X 10-9 M) than to estrogen receptor (Ki divide 2.6 X 10-6 M), (d) while ENT is bound to progestogen and estrogen receptors at the same time, Bm of ENT (8.7 X 10-8 M/mg of cytosol protein) is more than Bm of progesterone (5.0 X 10-9 M/mg of cytosol protein), and Kd of ENT (1.1 X 10-9 M) was less than Ki of ENT (2.3 X 10-9 M) in the binding to progesterone-receptor. Biologically, while ENT is bound to progestogen -receptor with high affinity and to estrogen receptor with low affinity, ENT is actually progestational in low dose and antiestrogenic in high dose but the anti-estrogenicity seems to be incomplete in vivo as ENT may be metabolized to a potent estrogenic compound, ethinyl estradiol
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PMID:[Interaction of norethindrone on estrogen and progesterone receptors in the rabbit uterine cytosol (author's transl)]. 18 90

Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.
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PMID:Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. 20 80

Estradiol treatment of ovariectomized-adrenalectomized rats produced an increase in cytosol progestin binding in the hypothalamus-preoptic area (HPOA), pituitary, and uterus. In the HPOA and pituitary, this induction of progestin receptors by estradiol was inhibited by the antiestrogen CI-628 under a variety of dose and time conditions. In the uterus, inhibition of the full effect of estradiol on progestin binding was observed after 3 days of injection of antiestrogen and estradiol. In the absence of estradiol, the antiestrogen produced a slight induction of progestin receptors in the HPOA and pituitary and a substantial induction of progestin receptors in the uterus. The results suggest that the induction of progestin receptors could be a key intermediate step in some behavioral and neuroendocrine actions of estradiol.
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PMID:Antiestrogen inhibits the induction of progestin receptors by estradiol in the hypothalamus-preoptic area and pituitary. 22 31

Estradiol is shown to induce histidine decarboxylase and histamine to activate adenylate cyclase in the rat uterus. Cyclic AMP like histamine simulates the effect of estradiol, intensifying RNA synthesis and inducing glycolytic enzymes and uterus inhibition. It was found by autoradiography that 3H-estradiol is accepted by the nuclei of some myometrium cells, 3H-histamine by their cytoplasm and 3H-cAMP is selectively bound by endothelium cells of the uterus capillaries. The estradiol messengers (histamine and cAMP) seem to mediate hormonal effect of some uterus heterofunctional cells forming a kind of multicellular functional system.
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PMID:[Multiphasic regulatory system mediating the effect of estradiol in rat uterus]. 22 31

The estrogen receptor has been purified to homogeneity from calf uterus cytosol by sequential affinity chromatography by using heparin--Sepharose 4B and 17-hemisuccinyl-17beta-estradiol-ovalbumin--Sepharose 4B. The procedure yields about 1.2 mg of receptor protein from 1 kg of calf uteri, with a recovery of 53%. The receptor protein, as a complex with 17beta-[3H]estradiol, is purified more than 99%. A single band is seen on polyacrylamide gel ectrophoresis under nondenaturing conditions. 17beta-[3H]Estradiol comigrates with the protein band. As computed from the specific activity of radioactive hormone, 64,450 g of purified receptor protein binds 1 mol of 17beta-estradiol. 17beta-[3H]Estradiol bound to the protein is displaced by estrogenic steriods but not by progesterone, testosterone, or cortisone. As judged by chromatography on calibrated Sephadex G-200 columns, the purified receptor is identical with native receptor in crude cytosol: both show a Stokes radius of 6.4 nm. On sucrose gradient in low-salt buffer, the purified receptor sediments at 8 S. On electrophoresis in NaDodSO4 gels, the purified receptor migrates as a single protein band with an apparent molecular weight of 70,000. The sedimentation coefficient measured on sucrose gradients in the presence of chaotropic salts [1 M NaBr or NaSCN (0.1 M)] is 4.2 S. We conclude that the estrogen receptor of cytosol consists of a single subunit weighing about 70,000 daltons and endowed with one estrogen binding site. Under native conditions in cytosol, several subunits associate to form a quaternary structure with a Stokes radius of 6.4 nm.
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PMID:Estrogen-binding proteins of calf uterus. Purification to homogeneity of receptor from cytosol by affinity chromatography. 44 62

The synthesis of biospecific adsorbents for the purification of the cytosol estrogen receptor from calf uterus is described. The characteristic of several estradiol derivatives, spacer chains, and insoluble matrix were systematically studied. Estradiol derivatives substituted at positions C2, 3, 4 7 alpha, 17 alpha, and 17 beta were tested for their affinities for the receptor; positions 7 alpha and 17 alpha were the most suibable. Acidic compounds had lower affinities than their methylester analogues. Long chain derivatives bound the receptor less firmly than corresponding shorter chains. However, when these ligands were attached to an insoluble matrix, the long spacer chain derivatives (greater than or equal to 14 atoms) were more efficient than the shorter ones. There was a satisfactory parallelism between affinities of free ligands and receptor binding to the respective biospecific adsorbents. On the basis of their stability in the presence of cytosol (no release of ligand), due to the absence of ester bonds, long chains were selected as spacers. Both acrylamide and agarose biospecific adsorbents displayed some ionic exchange capacity and consequently nonspecifically bound proteins; the influence of this nonspecific binding on the purification of the receptor was studied. On the basis of their stability, of their binding specificity, and of their selectivity for the receptor, the estradiol-7 alpha derivative adsorbents were selected for the purification of the receptor.
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PMID:New biospecific adsorbents for the purification of estradiol receptor. 55 54


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