Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Progesterone inhibited D-amino acid oxidase (D-amino acid : O2 oxidoreductase (deaminating), EC 1.4.3.3) in competition with its substrate, D-alanine. Binding of progesterone brought about the increase in both fluorescence intensity and fluorescence polarization of FAD, which indicates that the environment surrounding FAD chromophore is modified due to a conformational change in the apoenzyme. 2. Ethinyl estradiol, testosterone, testosterone propionate, corticosterone and aldosterone also inhibited the enzyme slightly in the same manner. Their binding also produced a slight increase in FAD fluorescence without decreasing the fluorescence polarization. 3. Cholesterol did not inhibit the enzyme, though it increased the fluorescence polarization of FAD. This indicates the binding of cholesterol with the enzyme at a site other than the substrate binding site.
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PMID:Interaction of steroids with D-amino acid oxidase. 2 64

Cells of sarcoma 180 and of Ehrlich's carcinoma were maintained by serial transplantation in male and female Swiss mice. Either estrogen, progesterone, or testosterone were injected im at doses of 1 mg/mouse. Ascitic fluid was aspirated at intervals of 1, 3, 6, 24, and 48 hours following hormone injections. Enzyme activities were analyzed by subjective grading according to the intensity of staining reaction. Estrogen produced enhancement of alkaline phosphatase activity in both types of cells in both sexes of mice. Progesterone produced increased alkaline phosphatase activity in both types of cells from female hosts but an inhibitory effect in male hosts' cells. Testosterone produced no change in enzyme activity in tumor cells of female hosts but in male hosts it inhibited enzyme activity of sarcoma 180 cells and activated activity in carcinoma cells. The effect of all 3 hormones on acid phosphatase activity was activation. With adenosine triphosphatase, estrogen stimulated the activity in both types of tumor in both sexes. Progesterone stimulated cells from male hosts with little or no effect on cells from female hosts. This enzyme was resistant to testosterone. Succinate dehydrogenase activity under similar conditions was different. Estrogen reduced this activity and progesterone produced some inhibition of activity. Testosterone inhibited the sarcoma cells but had no effect on carcinoma cells of either sex. Others have shown that sex hormones affect the enzyme activities beyond the target tissues, particularly in the liver, kidney, and pancreas. Different responses of the enzymes seemed to depend on the endogenous hormonal status of the mice.
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PMID:Enzymatic responses of transplanted tumour cells towards estrogen, progesterone and testosterone. 13 8

Currently available forms of hormonal contraceptives with regard to their mechanism of action, effectiveness, and side effects are reviewed. The effectiveness of an oral contraceptive in preventing pregnancy is directly related to its ability to inhibit ovulation. Other effects are less important. The development of synthetic progestational agents made inhibition of ovulation possible without unacceptable side effects. The chemical structures of several estrogens are shown and their relationship to natural estrogen indicated. The chemical structures of synthetic progestational agents and their relationship to progesterone and testosterone are illustrated. Diethylstilbestrol is a nonsteroidal estrogenic compound with a potency of 1/25 of that of ethinyl estradiol. It is used only as a postcoital contraceptive for occasional use. Medroxyprogesterone acetate is a long-lasting injectable contraceptive agent. Available oral contraceptive preparations are listed by brand names, hormone content, and tablet amount. With combination compounds a 28-day routine of therapy has been established. In recently developed compounds the amount of hormone used has been reduced so that side effects are less. The pregnancy rate is less than .1%. The very low-dose preparations have a higher pregnancy rate and an increased incidence of intermenstrual bleeding. The sequential-type oral contraceptive is no longer available. The progestin-only type contains no estrogen, and they are taken continuously. They do not prevent ovulation. Their contraceptive effect is by alterations in cervical mucus and endometrial or tubal physiology. The pregnancy rate is relatively high. No single preparation is considered as suitable for all women. Patients with varicose veins or previous thromboembolic phenomena should not use any oral contraceptive. The combination preparations are most suitable for the majority of women.
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PMID:Hormonal contraception: current perspectives. Part I. An analysis of available agents. 14 41

Cholesterol and triglycerides were measured in plasma samples from patient with cancer of the prostate before and after 3 months treatment with either Premarin, Provera, Provera and diethylstilbestrol, or diethylstilbestrol alone. Cholesterol was also measured before and after one of three doses of diethylstilbestrol or placebo. Pretreatment cholesterol levels at 196 +/- 1.3 mg per 100 ml (X +/- SE, N = 1093) were significantly lower than these reported for similar age group noncancer controls. Significant increases occurred with some of the estrogen treatments. Pretreatment cholesterol levels showed a significant negative correlation with age in Stage III and IV patients of both studies and a positive correlation with hemoglobin in Stage III patients of both studies. Pretreatment triglyceride levels at 120 +/- 1.9 mg per 100 ml (X +/- SE, N = 1089) were similar to levels reported for noncancer controls of similar age. Estrogen treatment produced a significant increase in triglyceride levels. Serum triglycerides were significantly correlated with hemoglobin, weight, and cholesterol and negatively correlated with age, Analysis of covariance for both cholesterol and triglycerides showed highly significant treatment effects, but no stage effects and no stage-treatment interactions. It showed that the pretreatment value is of extreme importance for predicting or explaining the 3-month value. Death rates were calculated by level of pretreatment cholesterol or pretreatment triglycerides for all Stage II and IV patients, all treatments combined, and for Study 2 and Study 3 separately. No consistent trends were evident for cholesterol. Spearman correlation coefficients between category of initial triglyceride value and rank of death rate were computed to test for a quadratic effect. When the absolute values of the initial triglyceride values minus the overall mean were correlated with the death rate, a significant negative correlation was found for all causes of death and for deaths due to cardiovascular disease and prostatic cancer. These results indicate that the death rate is highest near the overal mean for initial triglyceride values and decreases as the initial values deviate above or below the mean. Initial triglyceride levels appear to have potential as indicators of risk of death in patients with prostatic cancer. The percentage of patients dead at 1 year by initial triglyceride levels, measured only in Study 3, revealed a pattern similar to that observed for the death rate, that is, the highest percentages were associated with values near the overall mean.
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PMID:Response of serum cholesterol and triglycerides to hormone treatment and the relation of pretreatment values to mortality in patients with prostatic cancer. 18 47

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

Estrogen priming increases uterine 8S macromolecule which binds progesterone specifically. Progesterone-8S complex in the cytoplasm enters into nucleus and is bound to chromatin finally. In this paper, the mode of nuclear translocation of steroid in exchange assay of receptor introduced by Anderson et al., and the mode of binding to chromatin were studied on the progesterone-receptor complex in the uterus of estrogen primed female rabbit. 1. After intravenous administration of 200 mug progesterone into the estrogen primed immature rabbit, uterine nuclei were prepared by the method in Table 1. These nuclei were incubated with 3H-progesterone and cold steroids at 4 degrees C for 30 minutes, and then washed with buffer A. The radioactivity of the nuclei was counted. This experiment was performed at 4 degrees C because progesterone receptor and chromatin were observed to be degraded at 37 degrees C for 20 minutes. The effect of cold steroids in vitro on the incorporation of 3H-progesterone into the uterine nuclei of rabbit pretreated with progesterone was found to be similar to their effect on progesterone-receptor binding in cytosol or chromatin (Fig. 1). 2. The effect of cold steroids on 3H-progesterone-receptor-chromatin triplex (Table 2 and Fig. 2) was examined. Once 3H-progesterone-receptor-chromatin triplex was formed, it was difficult to exchange 3H-progesterone to other steroids at 4 degrees C. These results (1 & 2) indicate that progesterone-receptor complex enters into nucleus and is bound to chromatin. Exchange of steroid may occur in the nuclear progesterone-receptor complex, which is free from the binding with chromatin. And thus exchange assay cannot represent quantitative data on receptor content. 3. 3H-progesterone-8S or 5S complexes were obtained by 5 approximately 20% sucrose linear gradient centrifugation (Fig. 3). The same molar concentration of these complexes from estrogen primed or castrated rabbit uterus were incubated with primed uterine chromatin for 30 minutes. Then the chromatin was washed with buffer A and the radioactivity was counted. It was shown in Fig. 4 that 3H-progesterone-8S complex was bound to chromatin much more tightly than 3H-progesterone 5-S complex in preparations obtained from both castrated or primed uterine cytosols. All these results indicate that 8S may be the biologically active form of the receptor. 4.3H-progesterone uptake into uterine nuclei was observed in very limited amount following the injection into uterine artery. The radioactivity in nuclei decreased easily by washing with buffer A as in Fig. 5. The small amount of residual radioactivity after washing, that is, very limited number of binding sites with high affinity is considered to be indicative of biologically active binding.
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PMID:[Studies on progesterone receptor in rabbit uterine cytosol -- nuclear translocation and chromatin binding-- (author's transl)]. 18 91

Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.
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PMID:Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry. 22 20

The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.
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PMID:Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats. 23 7

Uterine progesterone receptors are under dual hormonal control. Estrogen increases the concentration of receptor through a mechanism that depends on synthesis of both RNA and protein. Progesterone decreases the concentration of its own receptor, probably by enhancing its inactivation rate. This regulation explains receptor variations during the estrous cycle. In both guinea pig and rat uteri, cytosol receptor concentration is maximal at the preovulatory period and decreases after ovulation. Nuclear receptor was measured in the rat. Its concentration is also maximal at proestrus, but the higher nuclear to cytosol receptor ratio was observed at metestrus. There is a good correlation (r = 0.78) between nuclear receptor concentration, on one hand, and the product of cytosol receptor concentration times the plasma progesterone concentration, on the other hand. Autoradiographic studies show that receptor variations during the estrous cycle occur simultaneously in all cell types of uterine horn, cervix, and vagina, which suggests that similar mechanisms control receptor concentration in all of these cells. Progesterone receptor was also measured during pregnancy in rat uterus. Cytosol receptor concentration is low at the beginning of pregnancy (approximately 6000 binding sites per cell), declines slightly on Day 5 (approximately 4000 binding sites per cell), and then increases progressively during the remainder of pregnancy to attain its highest value on Day 22 (26,000 binding sites per cell). Nuclear receptor concentration is very low on Day 3 (1200 binding sites per cell), increases slightly on Day 5 (1900 binding sites per cell), decreases on Day 6, and then increases again to attain a plateau between Days 9 and 15 (approximately 2600 binding sites per cell). Thereafter, its concentration begins to decrease rapidly. On Day 22, the mean concentration is very low (700 binding sites per cell); in some animals (probably on the verge of parturition), no nuclear receptor can be detected.
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PMID:Hormonal control of progesterone receptors. 28 Nov 73

Estrogen stimulates development of mammary ducts, and progesterone and estrogen stimulate proliferation of secretory tissues. In vivo, sequential addition of insulin (step 1), glucocorticoid (step 2), and prolcatin (step 3) leads to biosynthesis of casein and lactose. In cows, mammogenesis continues until termination of pregnancy and overlaps onset of lactation. Progesterone probably inhibits differentiation of secretory cells at step 2 or step 3. Sensitivity of individual cells to progestational inhibition may decrease variably which may be interdependent upon relative increases in estrogen, prolactin, corticoids, and growth hormone to cause asynchronies among them at calving. Since prolactin in plasma is not correlated with progesterone or the estrogens, factors other than feed-back effects of ovarian steroids may be responsible for its sustained increase periparturiently. Also, elevated prolactin periparturiently may be unrelated to subsequent rates of lactation because its "basal" concentrations may meet requirements when inhibiting effects of progesterone are removed. This concept is attractive because mammary cells neither are synchronized highly for biosynthesis nor secrete normal milk for several days after calving. At the latter time, concentrations in plasma are low for progesterone and estrogen, similar to 3 days before calving for glucocoiticoids and prolactin, and increasing for insulin. Evidence of lactation under unusual circumstances was discussed.
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PMID:Hormonal control of mammogenesis and onset of lactation in cows--a review. 40 1


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