GATA-4 and GATA-6 modulate tissue-specific transcription of the human gene for P450c17 by direct interaction with Sp1.

Cytochrome P450c17 catalyzes steroidogenic 17alpha-hydroxylase and 17,20 lyase activities. Expression of the gene for P450c17 is cAMP dependent, tissue specific, developmentally programmed, and varies among species. Binding of Sp1, Sp3, and NF1-C (nuclear factor 1-C) to the first 227 bp of 5'flanking DNA (-227/LUC) is crucial for basal transcription in human NCI-H295A adrenal cells. Human placental JEG-3 cells contain Sp1, Sp3, and NF1, but do not express -227/LUC, even when transfected with a vector expressing steroidogenic factor 1 (SF-1). Therefore, other factors are essential for basal expression of P450c17. Deoxyribonuclease I footprinting and EMSAs identified a GATA consensus site at -64/-58 and an SF-1 site at -58/-50. RT-PCR identified GATA-4, GATA-6, and SF-1 in NCI-H295A cells and GATA-2 and GATA-3, but not GATA-4, GATA-6, or SF-1 in JEG-3 cells. Cotransfection of either GATA-4 or GATA-6 without SF-1 activated -227/LUC in JEG-3 cells, but cotransfection of GATA-2 or GATA-3 with or without SF-1 did not. Surprisingly, mutation of the GATA binding site in -227/LUC increased GATA-4 or GATA-6 induced activity, whereas mutation of the Sp1/Sp3 site decreased it. Furthermore, promoter constructs including the GATA site, but excluding the Sp1/Sp3 site at -196/-188, were not activated by GATA-4 or GATA-6, suggesting an interaction between Sp1/Sp3 and GATA-4 or GATA-6. Glutathione-S-transferase pull-down experiments and coimmunoprecipitation demonstrated interaction between GATA-4 or GATA-6 and Sp1, but not Sp3. Chromatin immunoprecipitation assays confirmed that this GATA-4/6 interaction with Sp1 occurred at the Sp site in the P450c17 promoter in NCI-H295A cells. Demethylation with 5-aza-2-deoxycytidine permitted JEG-3 cells to express endogenous P450c17, SF-1, GATA-4, GATA-6, and transfected -227/LUC. Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells.

The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway.

Cytochrome P450c17 catalyzes both 17alpha-hydroxylation and 17,20-lyase conversion of 21-carbon steroids to 19-carbon precursors of sex steroids. P450c17 can mediate testosterone biosynthesis via the conversion of pregnenolone to dehydroepiandrosterone (the delta(5) pathway) or via conversion of progesterone to androstenedione (the delta(4) pathway). In many species, the 17, 20-lyase activity of P450c17 for one pathway dominates, reflecting the preferred steroidogenic pathway of that species. All studies of recombinant human P450c17 and of human adrenal microsomes have found high 17, 20-lyase activity only in the delta(5) pathway. Because the 17, 20-lyase activities in both the delta(4) and delta(5) pathways for testicular P450c17 have not been directly compared, however, it is not known if the delta(5) pathway dominates in the human testis. To resolve this issue, we assayed the conversion of 17alpha-hydroxypregnenolone to dehydroepiandrosterone (delta(5) 17, 20-lyase activity) and of 17alpha-hydroxyprogesterone to androstenedione (delta(4) 17, 20-lyase activity) by human fetal testicular microsomes. We obtained apparent Michaelis constant (K(m)) and maximum velocity (V(max)) values of 1.0 microM and 0.73 pmol.min(-1). microg(-1) for delta(5) 17, 20-lyase activity and of 3.5 microM and 0.23 pmol.min(-1). microg(-1) for delta(4) 17, 20-lyase activity. Catalytic efficiencies, expressed as the ratio V(max)/K(m), were 0.73 and 0.066 for the delta(5) and delta(4) reactions, respectively, indicating 11-fold higher preference for the delta(5) pathway. We conclude that the majority of testosterone biosynthesis in the human testis proceeds through the conversion of pregnenolone to dehydroepiandrosterone via the delta(5) pathway.

Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.

The ACTH receptor (MC2R) is expressed predominantly in the adrenal cortex, but is one of five G protein-coupled, seven-transmembrane melanocortin receptors (MCRs), all of which bind ACTH to some degree. Testing of MC2R activity is difficult because most cells express endogenous MCRs; hence, ACTH will elicit background activation of assayable reporter systems. Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH, also known as familial glucocorticoid deficiency (FGD). These patients are usually seen in early childhood with very low cortisol concentrations, normal mineralocorticoids, hyperpigmentation, and increased bodily growth. Several MC2R mutations have been reported in FGD, but assays of the activities of these mutants are cumbersome. We saw two patients with typical clinical findings of FGD. Genetic analysis showed that patient 1 was homozygous for the mutation R137W, and patient 2 was a compound heterozygote for S74I and Y254C. We tested the activity of these mutations in OS-3 cells, which are unresponsive to ACTH but have intact downstream cAMP signal transduction. OS-3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc) were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40-fold. Addition of ACTH to cells cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is similar to previously reported values. By contrast, the MC2R mutant R137W had low activity, and the S74I or Y254C mutants elicited no measurable response. This assay provides excellent sensitivity in an easily assayed transient transfection system, providing a more rapid and efficient measurement of ACTH receptor activity.

Jodocus Hondius en Hugh Broughton : bijdrage tot de kennis der eerste Hebreeuwsche uitgaven in Amsterdam

Aus: Het boek ; [17.] 1928

Offenbacher Haggadah [Rezension]

A. L.

Die religiösen Grundlagen im Lichte des Christentums und des rabbinischen Judentums

Walter J. Fischel

[Rezension]

L. Bergsträßer

Na 1 Nachlass Max Horkheimer, 12 - Korrespondenzen u.a. mit Carl Dreyfuss (p. I 6, 184-311)

1 Brief von Max Horkheimer an die Zeitschrift The Dog's World, 05.06.1939; 5 Briefe zwischen John Dollard und Max Horkheimer, 1936-1938; 16 Briefe zwischen Josef Doppler und Max Horkheimer, 1934-1939; 2 Briefe zwischen Walter Dorn und Max Horkheimer, 27.09.1941, 24.03.1942; 2 Briefe zwischen Melvyn Douglas und Max Horkheimer, 02.03.1942, 18.12.1941; 34 Briefe zwischen Carl Dreyfuss und Max Horkheimer, 1937-1939; 1 Brief von der National City Bank of New York an den American Consul General London, 15.10.1937; 1 Brief und 2 Entwürfe von Max Horkheimer an den Americal Consul General London, 10.09.1937; 4 Briefe zwischen Walter Dubislav und Max Horkheimer, 1936, 02.10.1936; 3 Briefe zwischen A. E. Duncan-Jones und Max Horkheimer, 1938, 13.04.1938; 1 Brief von E. Duprée an Max Horkheimer, 04.02.1936; 2 Briefe zwischen Bonté Durán und Max Horkheimer, 15.04.1941;

Na 1 Nachlass Max Horkheimer, 63 - Korrespondenzen u.a. mit der American Philosophical Association (p. II 3, 1-132)

Drucksachen und Briefwechsel von der American Philosophical Association, 1942-1949; 2 Briefe von Max Horkheimer an Eugene N. Anderson, 25.05.1942; 1 Briefabschrift an Franz Neumann, 29.04.1942; 3 Briefe zwischen Walter L. Arensberg und Max Horkheimer, 1941; 17 Brief und Beilagen zwischen Aufbau [Zeitschrift] und Max Horkheimer, 1942-1948; 8 Briefe und Beilage ziwschen Bruno Franco Avardi und Max Horkheimer [Pollock], 1942-1943; 21 Briefe und Beilage zwischen Edward N. Barnhart von der University of California und Max Horkheimer, 1947-1949; 5 Briefe zwischen Salo W. Baron und Max Horkheimer, 1945; 5 Briefe zwischen Gertrude Bauer und Max Horkheimer, 1941-1946; 1 Brief und Beilage von Ralph L. Beals von der University of California an Max Horkheimer, 1947-1948; 5 Briefe zwischen Howard Becker und Max Horkheimer, 1948; 1 Brief und Beilage von Frank Beckwith an Max Horkheimer, 1944; 1 Brief zwischen Bruno Bettelheim und Max Horkheimer, 1944-1949 sowie 1 Manuskript von Bruno Bettelheim: The Thematic Apperception Test as an Educational and Therapeutic Device;

Na 1 Nachlass Max Horkheimer, 571 - Korrespondenzen mit Franz Neumann (p. VI 30, 1-224)

169 Briefe zwischen Franz Neumann und Max Horkheimer; 4 Briefe von Franz Neumann an Frederick Pollock, 1937 - 1941; 7 Briefe zwischen Franz Neumann und Walter L. Dorn, 1941 - 1942; 2 Briefe zwischen Walter L. Dorn und Max Horkheimer, März 1943; 1 Brief von Tom an Franz Neumann, 09.09.1941; 1 Brief von Phillip C. Jessup an Franz Neumann, 22.08.1941; 1 Brief von Athur und Wicky Goldschmidt an Franz Neumann, 22.08.1941; 2 Briefe von Goodwin Watson an Franz Neumann, 1941; 1 Brief von Harold Lasswell an Franz Neumann, 07.07.1941; 2 Briefe von Eugene N. Anderson an Franz Neumann, 1941; 1 Brief von C. J. Friedrich an Franz Neumann, 18.06.1941; 1 Brief von Alfred E. Cohn an Max Horkheimer, 30.01.1941; 1 Brief von Alfred E. Cohn an Franz Neumann, 30.01.1941; 3 Briefe von Leo Löwenthal an Franz Neumann, 1940; 1 Brief von Thurman Arnold an Max Horkheimer, 21.12.1938; 2 Briefe zwischen Ernst Kahn und Franz Neumann, 1938; 1 Brief von Franz Neumann an Walter Socoloff, 21.06.1938; 1 Brief von Franz Neumann an Flegenheimer, 31.06.1935; 1 Brief von Anita [Schwester von Felix Weil] an Felix Weil, 24.08.1937; 2 Briefe zwischen Franz Neumann und C. D. Medley, 1935/1936; 7 Briefe zwischen The Emergency Committee in Aid of Displaced German Scholars (New York) und Max Horkheimer, 1936; 1 Brief von Max Horkheimer an Guerreo, 08.09.1936; 1 Brief (Abschrift) von der Columbia University (New York) an United States of America, Consul General (London), 05.03.1936; 1 Brief von Franz Neumann an Juliette Favez, 11.12.1935;

Na 1 Nachlass Max Horkheimer, 572 - Korrespondenzen mit Franz Neumann und Friedrich Pollock (p. VI 30, 225-484)

169 Briefe zwischen Franz Neumann und Max Horkheimer; 7 Briefe zwischen Walter L. Dorn und Franz Neumann, 1941 -1942; 2 Briefe zwischen Max Horkheimer und Walter L. Dorn, März 1943; 1 Brief von dem U. S. Department of Justice an Max Horkheimer, 13.07.1942; 1 Brief von Max Horkheimer an John R. Brooks, 30.08.1947; 1 Brief an Robert (Bob) Schmid von Franz Neumann, 06.05.1947; 1 Brief an Franz Neumann von James E. Murray, 05.06.1942; 21 Briefe zwischen Friedrich Pollock und Max und Maidon Horkheimer, 1911-1921; 1 Brief von Max Horkheimer an Andrée, 01.12.1918;

Documents relating to reconstruction,

Issued in numbers as West Virginia university documents relating to reconstruction. Nos. 4-5 and 6-7 pub. as double numbers.

Christmas carols; old English carols for Christmas and other festivals.

"Published, autumn 1922."

Trust administration and taxation /

Mode of access: Internet.