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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homogenates from human myometrium with an added NADPH regenerating system and ATP were incubated with 4-(14)C progesterone. Six metabolites were identified: 5alpha-pregnane-3, 20-dione, 5beta-pregnane-3, 20-dione, 3alpha-hydroxy-4-pregnen-20-one, 3beta hydroxy-4-pregnen-20-one. 20alpha-hydroxy-4-pregnen-3-one and 20beta-hydroxy-4-pregnen-3-one. The identification of these metabolites was based on their behaviour in paper and thin layer chromatography and especially in radiogaschromatography either as free compounds or after formation of derivatives. The identification of the two allylic metabolites was supplemented by specific microchemical and enzymatic reactions. The formation of 5beta-pregnane-3, 20-dione, 20beta-hydroxy-4-pregnen-3-one and of the two allylic alcohols 3alpha-hydroxy-4-pregnen-20-one and 3beta-hydroxy-4-pregnen-20-one in human myometrium homogenates was demonstrated for the first time.
Steroids 1977 Jul
PMID:New progesterone metabolites in human myometrium. 91 10

The 15-azasteroid, 1,10,11,11a-tetrahydro-11a-methyl-2H naphth (1,2-g)indol-7-o1, inhibits the growth of the cell culture lines KB and L-M as well as several strains of bacteria. The inhibition of growth is reversed following removal of the steroid from the growth medium. Using in vitro grown L-M cells, the compound inhibited the transport of amino acids and uracil. The action was non-detergent like and at least 100 times more effective in terminating metabolite transport than sodium azide. The azasteroid inhibited the oxidation of glutamate in isolated rat liver mitochondria. The oxidation of succinate was not effected by the azasteroid alone but in the presence of glutamate, the azasteroid uncoupled the oxidation of succinate from the ADP-ATP control. It is suggested that the azasteroid may be acting directly on the electron transport system and/or acting indirectly through membrane perturbations which disrupts the electron transport process.
Steroids 1976 Oct
PMID:15-Azasteroid blockage of cell permeability and mitochondrial respiration. 100 23

The biotransformation of estradiol (E2) and estrone (E1) in the uterus of rabbits treated with norgestrel (NG), norethindrone (NET), norethindrone acetate (NETA), progesterone (P4), and E2 either by subcutaneous injection in oil or by intrauterine steroid-releasing silastic implants was carried out under an in vitro short-term incubation system. The studies have shown that E2 stimulates 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSD) much more than P4 as compared to untreated controls. The kinetic studies on E2 metabolism in the presence of added coenzyme NAD showed an initial rapid estrone formation and a gradual reconversion of E1 to E2. The addition of NADPH, ATP, and glucose-6-phosphate facilitates the reconversion of E1 to E2. The interconversion of E2 and estrone in the presence of coenzymes was five- to ten-fold higher in the endometrium than in the myometrium per milligram protein. Both E2 and progestins stimulate the uterine 17 beta-OHSD activity in rabbit uterus. This study further suggested that the hormone-induced metabolism of estradiol and estrone in the rabbit uterus is essentially modulated by the availability of coenzymes.
Steroids 1989 Jun
PMID:Effect of progestins, estradiol, and coenzymes NAD and NADPH on the interconversion of estradiol and estrone in rabbit uterus in vitro. 255 42

In the present study the possible dual effects of adenosine as substrate and adenosine receptor agonist in rat granulosa cells, cumulus-oocyte complexes, luteal cells and ovarian membranes are discussed. Adenosine is an indispensable compound in cell energy metabolism, as precursor to cofactors, second messenger and nucleic acids. Adenosine is also an agonist to adenosine receptors. The adenosine receptor can either inhibit (A1) or stimulate (A2) adenylate cyclase. Alternatively, in some cells adenosine receptor activation is linked to other cellular events like inhibition of Ca2+ fluxes. Adenosine is taken up by isolated preovulatory granulosa and luteal cells from pregnant mare serum gonadotropin-treated immature rats, but follicle stimulating hormone (FSH) decreases the uptake by granulosa cells. Adenosine, but not the non-metabolizable adenosine analogs 5'-(N-ethyl)carboxamide-adenosine (NECA), 2-chloro-adenosine (2-Clado), N6-(R-phenyl-isopropyl)-adenosine (R-PLA) and N6-(S-phenyl-isopropyl)-adenosine (S-PLA), increase granulosa cell ATP levels. FSH and luteinizing hormone (LH) decrease granulosa cell ATP levels in the presence or absence of adenosine. It has previously been shown that FSH and LH decrease oxygen consumption by cumulus-oocyte complexes and increase their lactate production. These effects have been suggested to be due to a competition of cofactors (e.g. ADP) common to glycolysis and the respiratory chain. The fact that adenosine reverse the gonadotropin-induced effects on oxygen consumption and lactate production support this theory. Adenosine and its analogs increase cAMP accumulation in luteal and granulosa cells only in the presence of gonadotropins, and this effect is antagonized by the adenosine receptor antagonist 8-phenyl-theophylline (8-PHT). Furthermore, adenylate cyclase is stimulated by adenosine analogs in membranes from non-luteinized and luteinized ovarian membranes and in luteal cell homogenates. The effect of NECA is antagonized by 8-PHT. In the membranes, the rank order of potency was NECA greater than 2-Clado greater than R-PLA greater than S-PLA, suggesting adenosine A2 receptors. In summary, it is suggested that adenosine can act both as a substrate to intracellular metabolism and as an adenosine A2 receptor agonist in granulosa and luteal cells. A paracrine short loop positive feedback model is proposed where extracellular adenosine, derived from a gonadotropin-induced extracellular increase in cAMP and a decrease in cellular ATP, enhances gonadotropin stimulation in granulosa and luteal cells.
Steroids 1989 Nov
PMID:Adenosine as substrate and receptor agonist in the ovary. 255

A number of diverse biological compounds involved in the regulation of the hypothalamo-hypophyseal-ovarian axis have been examined for effects on the conversion of 3H-progesterone to 3H-5 alpha-dihydro-progesterone and 3H-3 alpha-hydroxy-5 alpha-pregnan-20-one by female rat hypothalamus and/or anterior pituitary. Broken cell preparations were incubated with 3H-progesterone and NADPH, and product 5 alpha-reduced progestins were quantitated by reverse isotopic dilution analysis. Progesterone 5 alpha-reductase activity was reduced up to 50% in the presence of 10(-2) to 10(-3) M serotonin in both preparations. At 10(-3) M, various indoles including n-acetylserotonin, melatonin, 5-methoxytryptamine, 5-methoxytryptophol, and 5-hydroxyindole acetic acid decreased by 10 to 30% 5 alpha-reduced product formation. At 10(-2) M, carbamylcholine and norepinephrine were without effect, while 10(-2) M dopamine reduced by 20% the 5 alpha-reduction of progesterone only in pituitary homogenates. The LHRH protease inhibitor bacitracin (2 X 10(-3) M) decreased by 10 to 40% progesterone 5 alpha-reductase activity in both tissues. By itself, LHRH did not affect the 5 alpha-reduction of progesterone nor did it potentiate the bacitracin effect. In the presence of 1 mM ATP, 100 micronM cAMP and 100 micronM cGMP increased 5 alpha-reduced product formation in the hypothalamus by 19 and 14%. The gonadotropins LH and FSH and the prostaglandins E1, E2, F1 alpha, and F2 alpha were without effect. Thus, these results and others indicate that a number of cellular components and other factors can affect the in vitro 5 alpha-reduction of progesterone in broken cell preparations.
Steroids 1980 Sep
PMID:The effects of neurotransmitters and other cellular modulators and factors on hypothalamic and anterior pituitary delta 4-steroid (progesterone) 5 alpha-reductase activity. 610 99

The rate of steroid synthesis is regulated by the rate of transport of cholesterol to mitochondria. The transport process involves two elements of the cytoskeleton (microfilaments and intermediate filaments) and Ca2+/ calmodulin. Electron microscopy and immunofluorescence reveal that lipid droplets in which steroidogenic cholesterol is stored in the cytoplasm are tightly attached to vimentin intermediate filaments. Mitochondria are also attached to intermediate filaments. Ca2+/calmodulin is known to be essential for the steroidogenic response to ACTH and acts to increase transport of cholesterol to mitochondria. Ca2+/ calmodulin promotes phosphorylation of two important adrenal proteins: vimentin via its protein kinase and myosin light chain via the calmodulin-dependent light-chain kinase. In permeabilized adrenal cells Ca2+/calmodulin causes an ATP-dependent contraction of the cells. Phosphorylation of vimentin is known to cause breakdown of intermediate filaments. Electron microscopy reveals that actin filaments cross-link intermediate filaments in adrenal cells. It is proposed that ACTH has at least two second messengers, Ca2+/calmodulin and cAMP. Ca2+/calmodulin causes breakdown of vimentin filaments and activates a contractile event dependent on ATP and myosin light chain. These changes reorganize the cytoskeleton in such a way as to facilitate the interaction of lipid droplets with mitochondria, resulting in transport of cholesterol to these organelles and hence increased steroid synthesis.
Steroids 1997 Jan
PMID:The roles of calmodulin, actin, and vimentin in steroid synthesis by adrenal cells. 902 35

Progesterone synthesis in the corpus luteum is regulated primarily by luteinizing hormone which acts via the adenylate cyclase/cyclic AMP/protein kinase A signalling cascade. Protein phosphorylation therefore plays a key role in the regulation of steroidogenesis, but there are relatively few studies of the in situ phosphorylation of luteal cell substrates. This may in part reflect the difficulties inherent in measuring changes in protein phosphorylation in intact cells preloaded with 32P and difficulties in interpreting data obtained using broken cell preparations. We have now applied a method of stable permeabilization of luteal cell plasma membranes by exposure of cell populations to a high intensity electric field. Under optimum conditions (5 kV/cm, six discharges) electrical permeabilization reproducibly produced populations of luteal cells in which 70-80% of the cells were permeabilized, as assessed by Trypan blue exclusion and [14C] sucrose space measurements. Pores were stable for at least 1 h, and there were no ultrastructural changes to the cells that could be detected by transmission electron microscopy. Permeabilized cells showed rapid cyclic AMP-induced changes in phosphorylation of endogenous proteins when provided with [gamma - 32 P] ATP. Our results demonstrate that the electricity permeabilized luteal cell offers a useful model for studying intracellular events in steroidogenic stimulus-response coupling cascades.
Steroids 1997 Jul
PMID:Electrical permeabilization of rat luteal cells: in situ phosphorylation of endogenous protein. 925 93

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, canalicular multispecific organic anion transporter/multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transporter/multidrug resistance protein 2 has been suggested. Therefore, to examine the effect of hydrophobicity on the substrate specificity of canalicular multispecific organic anion transporter/multidrug resistance protein 2, we examined the effect of organic anions and bile acid conjugates on biliary excretion of three taurine-conjugated bile acid sulfates with different hydrophobicity, taurolithocholate-3-sulfate, taurochenodeoxycholate3-sulfate, and taurocholate-3-sulfate in rats. Biliary excretions of these bile acid conjugates were delayed in Eisai hyperbilirubinemic rats. Biliary excretion of these bile acid conjugates was inhibited by sulfobromophthalein, whereas biliary excretion and taurocholate-3-sulfate was not inhibited by phenolphthalein glucuronide. Taurolithocholate-3-sulfate and ursodeoxycholate-3-glucuronide decreased biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate, but ursodeoxycholate-3,7-disulfate did not affect biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate. These findings indicate that very hydrophilic organic anions are not good substrates of canalicular multispecific organic anion transporter/multidrug resistance protein 2.
Steroids 1999 Nov
PMID:Effect of organic anions and bile acid conjugates on biliary excretion of taurine-conjugated bile acid sulfates in the rat. 1057 37

Interactions between transmembrane and cytoplasmic domains of Ca2+-ATPase from sarcoplasmic reticulum (SR) have been studied. To affect the hydrophobic transmembrane domain, we used four amphiphilic steroids - esters of a dibasic acid and 20-oxypregnene. All four steroids contained cholesterol-like nuclei and differed by the structure of side chains. Steroids with carboxyl groups in the side chains inhibited the rates of ATP hydrolysis and Ca2+ transport, whereas a steroid without the carboxyl group did not appreciably affect Ca2+-ATPase function. Fluorimetric titration of FITC-labelled Ca2+-ATPase in SR vesicles by Nd3+ showed that steroids increased the apparent dissociation constant for Nd3+ bound to the hydrolytic site, the potency order of the steroids being the same as for the sterol-induced inhibition of the hydrolytic activity of Ca2+-ATPase. These results suggest structural changes in the active site. Ca2+ transport was inhibited more efficiently by steroids than the hydrolytic activity of the enzyme. This could be partially due to the increase of the membrane passive permeability induced by steroids, which, in turn, reflected the efficiency of the interaction of the steroids with lipid bilayers. The effects of the steroids were largely dependent on their amphiphilicity (the availability of polar groups in regions A and D), the structure of the side chains, and, possibly, on the distance between the molecular polar groups. We suggest that the inhibition of hydrolytic and transport functions of Ca2+-ATPase in the SR membrane is due to the interaction of the steroids with the transmembrane alpha-helical segments.
 ...
PMID:Steroid-induced conformational changes of FITC-labelled sarcoplasmic reticulum Ca2+-ATPase. 1149 6

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transport has been suggested. Ursodeoxycholic acid, the 7beta-epimer of chenodeoxycholic acid, is clinically used for various hepatobiliary diseases. In our previous study, the contribution of multidrug resistance protein 2 for biliary excretion of taurine-conjugated bile acid sulfates depended on the numbers of hydroxyl residue. Therefore, to further examine the effect of hydrophobicity on the substrate specificity of multidrug resistance protein 2, we examined the effect of bile acid conjugates and organic anions on biliary excretion of tauroursodeoxycholate-3-sulfate, taurine and sulfonate-conjugated ursodeoxycholic acid, in rats. Biliary tauroursodeoxycholate-3-sulfate excretions was markedly delayed in Eisai hyperbilirubinemic rats. Taurolithocholate-3-sulfate inhibited but ursodeoxycholate-3,7-disulfate did not affect biliary tauroursodeoxycholate-3-sulfate excretion. Biliary tauroursodeoxycholate-3-sulfate excretion was inhibited by sulfobromophthalein, but was not inhibited by dibromosulfophthalein and cefpiramide. These findings indicate that tauroursodeoxycholate-3-sulfate is very specific for multidrug resistance protein 2.
Steroids 2001 Sep
PMID:Biliary excretion of tauroursodeoxycholate-3-sulfate in the rat. 1154 58


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