Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of PCBs (mixture of 2, 3, 4, 5-tetra; 2, 2', 4, 5, 5'-penta; 2, 2', 3, 3', 6, 6'-hexa and 2, 2', 3, 3', 4, 4', 5, 5'-octa congeners) on androgen production were investigated by suspension of Leydig cells from adult rat testis. hCG-stimulated androgen production was significantly inhibited by PCBs while progesterone level was not affected. Progesterone supported testosterone production was also decreased by PCBs, while conversion of androstenedione to testosterone was unchanged. These results suggest that the activity of microsomal enzyme C21 side-chain cleavage P450 was decreased by PCB treatment of Leydig cells in vitro.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Effect of PCBs on androgen production by suspension of adult rat Leydig cells in vitro. 777 64

Limited proteolysis of intact yeast methionine aminopeptidase (MAP1) with trypsin releases a 34 kDa fragment whose NH2-terminal sequence begins at Asp70, immediately following Lys69. These results suggest that yeast MAP may have a two-domain structure consisting of an NH2-terminal zinc finger domain and a C-terminal catalytic domain. To test this, a mutant MAP lacking residues 2-69 was generated, overexpressed, purified and analyzed. Metal ion analyses indicate that 1 mol of wild-type yeast MAP contains 2 mol of zinc ions and at least 1 mol of cobalt ion, whereas 1 mol of the truncated MAP lacking the putative zinc fingers contains only a trace amount of zinc ions but still contains one mole of cobalt ion. These results suggest that the two zinc ions observed in the native yeast MAP are located at the Cys/His rich region and the cobalt ion is located in the catalytic domain. The kcat and Km values of the purified truncated MAP are similar to those of the wild-type MAP when measured with peptide substrates in vitro and it appears to be as active as the wild-type MAP in vivo. However, the truncated MAP is significantly less effective in rescuing the slow growth phenotype of map mutant than the wild-type MAP. These findings suggest that the zinc fingers are essential for normal MAP function in vivo, even though the in vitro enzyme assays indicate that they are not involved in catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1995 Jan 20
PMID:Evidence that two zinc fingers in the methionine aminopeptidase from Saccharomyces cerevisiae are important for normal growth. 786 96

Progesterone hydroxylase cytochrome P-450 was purified to homogeneity from Phycomyces blakesleeanus microsomes by a four step procedure. An M(r) value of 60,000 was determined for this protein by SDS-PAGE. The DEAE-cellulose and Blue-1 MIMETIC affinity fractions gave major peaks at 452 nm in a dithionite-reduced, carbon monoxide, difference spectrum. NaIO4-dependent progesterone hydroxylation was obtained by the pure enzyme without NADPH and NADPH-cytochrome P-450 reductase. NADPH-dependent hydroxylation required the addition of other Phycomyces microsomal proteins present in the Blue-1 fraction.
J Steroid Biochem Mol Biol 1995 Feb
PMID:Microbial transformation of steroids--IX. Purification of progesterone hydroxylase cytochrome P-450 from Phycomyces blakesleeanus. 787 54

The MAP kinase cascade is regulated by many hormones and growth factors and its activation leads to changes in properties of cytoplasmic, membrane-associated, and nuclear proteins. The MAP kinases themselves are activated by MEKS. MEKs lie at a point of convergence for multiple upstream signals, mediated by distinct protein kinases, Raf, MEK kinase, and Mos, all of which have MEK kinase activity. Additional inputs that stimulate the MAP kinase pathway are the activation of protein kinase C and the yeast protein kinase STE20. Mechanisms of regulation of some of the upstream components of this cascade have not yet been fully elucidated.
Cell Mol Biol Res 1994
PMID:Regulation of the MAP kinase cascade. 787 3

Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways.
Mol Cell Biol 1994 Nov
PMID:Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element. 793 70

We have described previously the presence of binding sites in particulate fractions of the porcine corpus luteum (CL) which were specific for progesterone. We now demonstrate the presence of similar progesterone-specific binding sites in particulate fractions of the ovine CL. Preincubation of ovine luteal membranes with radiolabelled steroids demonstrated binding of progesterone and pregnenolone to a low-density particulate fraction (1.07-1.09 g/cm3). Preincubation with digitonin perturbed the buoyant density of this fraction (to 1.10-1.14 g/cm3) without causing release of steroid. Androgens and oestrogens did not bind appreciably to control luteal membranes, but were bound when preincubated with digitonin. In contrast, steroid conjugates (oestrone sulfate, pregnanediol glucuronide), cortisol, fatty acids (arachidonic acid, prostaglandin F2 alpha) and cholesterol ester failed to bind to ovine luteal membranes, with or without digitonin pretreatment. The effects of digitonin on steroid binding led us to examine its effects on steroid binding to ovine luteal membrane fractions in vitro. Specific progesterone binding was absent in the absence of digitonin, even at very high membrane concentrations. However, binding of 3H-labelled progesterone was stimulated 5-15-fold in a dose-dependent fashion by increasing digitonin concentrations, reaching a plateau at about 100 microM. In the presence of digitonin, [3H]progesterone binding increased linearly with luteal membrane concentration. Other detergents, saponins and cardiotonic steroids tested did not stimulate progesterone binding to ovine luteal membranes. [3H]Progesterone binding was dependent on the pH, duration and temperature of incubation. Unlabelled progesterone decreased binding of [3H]progesterone (half-maximal displacement of specific binding (IC50) at about 60 nM) whereas androgens were less potent (IC50, 500-3300 nM), whilst a wide range of other steroids and inhibitors of steroidogenic enzymes were ineffective, except at very high concentrations. Similarly, a number of progesterone receptor agonist and antagonist analogues failed to compete for progesterone binding to luteal membranes, suggesting that these binding sites were unrelated to progesterone receptors. Modifications to the 3, 4, 5 and 11 positions of progesterone, removal of the steroid side-chain or aromatization of the A-ring decreased binding potency dramatically, whereas changes to the 17 or 20 positions had relatively minor effects. Our results indicate the presence of a low density particulate fraction in ovine corpora lutea which contains specific binding sites for endogenous and exogenous progesterone.
Mol Cell Endocrinol 1994 Jul
PMID:Particulate binding sites for steroid hormones in subcellular fractions of the ovine corpus luteum: properties and hormone specificity. 795 96

Porcine granulosa cells have been shown previously to both secrete and respond to insulin-like growth factor-I (IGF-I), suggesting an autocrine function of this peptide in the follicle. The present work was undertaken to determine possible effects of IGF-I on in vitro maturation, in vitro fertilization, and early embryonic development in culture. Granulosa and cumulus cell proliferation and differentiation based on 3H-thymidine uptake and progesterone production, respectively, were also assessed. The results showed that the cleavage rate of oocytes was markedly stimulated in a dose-dependent manner by the addition of IGF-I to the oocyte maturation medium (P < 0.05). Embryo development beyond the 8-cell stage was improved by IGF-I, reaching a maximum of 22% at 200 ng/ml IGF-I. Treatment with IGF-I after fertilization increased the percentage of total oocyte cleavage (P < 0.05) to approximately 52%, 43%, and 57% at, respectively, 25, 50, and 100 ng/ml IGF-I. 3H-thymidine incorporation by granulosa cells was significantly increased in cultures treated with FSH (3-fold) or IGF-I (6-fold) compared to the control. For the cumulus cells, FSH caused a similar increase (3-fold) in 3H-thymidine incorporation while IGF-I stimulated a 15-fold increase. Progesterone production by the granulosa cells was increased to the same extent by treatment with FSH or IGF-I (4.7 and 5.1-fold, respectively). However, for the cumulus cells, while FSH caused a marked 16-fold increase in progesterone production, IGF-I caused only a marginal increase of 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 Aug
PMID:Effect of IGF-I on pig oocyte maturation, fertilization, and early embryonic development in vitro, and on granulosa and cumulus cell biosynthetic activity. 798 Sep 45

Progesterone metabolism by guinea pig amnion, chorion, myometrium, and endometrium was studied at the following gestational stages. Day 45 represents mid-gestation, about 5 days before strong chorion interaction between the entire surface of the chorion and the uterus; days 57-58, 1-2 days after chorion attachment, and 2-3 days before the onset of pubic symphysis relaxation; days +1-+6, 1-6 days after the onset of pubic symphysis relaxation, i.e. within 1 week of parturition. The high metabolic activity of chorion exceeded that by amnion at all stages. Metabolism by endometrium and myometrium was always low. Conversion of progesterone by amnion significantly decreased (P < 0.05) between days 57-58 and days +1-+6. Progesterone metabolites produced by chorion and amnion were identified by TLC, HPLC, and capillary GC/MS. Both tissues converted progesterone to three major products during 60-min incubations. These were 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 3 beta-hydroxy-5 alpha-pregnan-20-one. The metabolite pattern differed between the two tissues. Three-minute incubations with chorion resulted in a significantly higher proportion of 3 alpha-hydroxy-4-pregnen-20-one (P < 0.01) and 5 alpha-pregnane-3,20-dione (P < 0.025) than at 60 min. The production of 3 beta-hydroxy-5 alpha-pregnen-20-one by chorion decreased (P < 0.05) between days 50-51 and 57-58. The ratio of 3 alpha-hydroxy-5 alpha-pregnan-20-one to 3 beta-hydroxy-5 alpha-pregnan-20-one increased (P < 0.05) between days 45 post-relaxation. The marked conversion of progesterone by chorion, or the formation of one or more of its metabolites, may serve to influence uterine function prior to delivery.
J Steroid Biochem Mol Biol 1994 Nov
PMID:Progesterone metabolism by guinea pig intrauterine tissues. 798 Nov 29

The effect of single or repetitive fluke-infections on rat liver steroid hormone metabolism was studied. Fascioliasis was induced by oral administration of 20 metacercariae of Fasciola hepatica to rats, by week-6 (mono-infected) or 12 and 6 (bi-infected), or 12, 9 and 6 (tri-infected) before killing. Total microsomal cytochrome P450 and P450 isoenzymes were measured spectrophotometrically and by Western-blot analysis, respectively. Progesterone and testosterone metabolism were quantified by normal phase high performance liquid chromatography. In control rats, progesterone and testosterone were mainly converted to 2 alpha- and 16 alpha-hydroxymetabolites. In the liver of mono-infected rats, hepatic cytochrome P450 was significantly decreased by 36-64% whereas the expression of all investigated isoenzymes was decreased by 36-82% with the exception of the unchanged P4502E1. 16 alpha- and 2 alpha-hydroxylations of progesterone and testosterone were significantly decreased by 50-90%, these decreases were correlated with those of P4502B1/2 and P4502C11 isoenzymes, respectively. In bi- and tri-infected rats, steroid hormones were metabolized similarly to control rats. The return of steroid drug metabolizing enzyme activities to control level could be related to the immune response associated to the development of the animal resistance to the parasitic infection.
J Steroid Biochem Mol Biol 1994 Nov
PMID:Consequences of challenge infections with Fasciola hepatica on rat liver P450-dependent metabolism of sex hormones. 798 Nov 30

Progesterone elicits a rapid, transient calcium influx in sperm that is a prerequisite for the progesterone-induced acrosome reaction. The possibility that the GABAA receptor/chloride channel was the receptor that mediated the progesterone-induced calcium influx in human sperm was examined. A-ring reduced 3 alpha-hydroxy pregnane steroids (e.g. alfaxalone, allopregnanolone, pregnanolone), which are active on the GABAA receptor/chloride channel, were found to be much weaker than progesterone at stimulating Ca2+ influx in sperm. The effects of a variety of progesterone metabolites and analogs and other steroids were compared for their ability to (i) stimulate GABA-induced 36Cl- uptake in synaptoneurosomes, (ii) stimulate GABA-induced Cl- currents in HEK-293 cells transfected with alpha 1, beta 2, and gamma 2 subunits of the GABAA receptor/chloride complex, and (iii) elicit a rapid Ca2+ influx in sperm. No correlation was observed between the ability of a given steroid to stimulate Ca2+ influx and efficacy in eliciting either 36Cl- uptake or chloride currents. Importantly, the action of progesterone to stimulate Ca2+ influx was not modified by GABA, diazepam, picrotoxin and pentobarbitol (known regulators of the GABAA receptor/chloride channel). It is concluded from these studies that the cell surface progesterone binding site on human sperm that mediates progesterone-induced changes in [Ca2+]i is unlike the steroid binding site on the GABAA receptor/chloride channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Sep
PMID:The cell surface progesterone receptor which stimulates calcium influx in human sperm is unlike the A ring reduced steroid site on the GABAA receptor/chloride channel. 798 50


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