The proposed investigations include three related areas: 1) the interaction of steroid hormone-receptor complexes with nucleotides; 2) influence of nucleotides in the process of transformation of cytosol receptors to a nuclear binding form; 3) the interaction of activated hormone-receptor complexes with nuclear components of the target tissues. Steroid rceptors have been shown to interact with ATP. This interaction has been studied in crude cytosol preparations from target cells for progesterone, estrogen and glucocorticoids. Efforts will be made to study this nucleotide-receptor interaction in purified progesterone receptor preparations. ATP presence has been shown to promote in vitro receptor activation at 0-4 C in salt-free conditions. The activated receptor shows increased affinity to bind to DNA-cellulose, isolated nuclei, and ATP-Sepharose. Studies will be performed to determine whether or not similar binding sites on the activated receptor are involved in their uptake by these receptors; and to investigate if the nucleotide-dependent activation of steroid-receptors involve physio-chemical changes similar to those brought about by conventional procedures like heat- and salt-activation. In recent years certain phosphatase inhibitors (molybdate, tungstate, vanadate) have been identified which stabilize the steroid-receptors but selectively block the process or receptor activation. These studies have advanced the hypothesis that phosphorylation and dephosphorylation of the receptor or a regulatory molecule may be involved in the process of steroid binding and receptor activation, respectively. Studies will be designed to test this hypothesis and to determine whether these phosphate inhibitors act directly by interacting with the receptor molecules. These studies are expected to provide correlation between such events as hormones binding, activation of steroid-receptor complex, and the interaction of the activated receptor with nuclear sites. Such information will enhance our understanding of the molecular aspects of the process of reproduction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK020893-07A1
Application #
3226823
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1978-12-01
Project End
1990-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Oakland University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Rochester
State
MI
Country
United States
Zip Code
48309
Cordoba-Chacon, Jose; Gahete, Manuel D; McGuinness, Owen P et al. (2014) Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice. Am J Physiol Endocrinol Metab 307:E928-34
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Hurd, C; Dinda, S; Khattree, N et al. (1999) Estrogen-dependent and independent activation of the P1 promoter of the p53 gene in transiently transfected breast cancer cells. Oncogene 18:1067-72
Dinda, S; Kodali-Gali, S; Sevilla, L et al. (1997) Inhibition of proliferation of T47D human breast cancer cells: alterations in progesterone receptor and p53 tumor suppressor protein. Mol Cell Biochem 175:81-9
Hurd, C; Khattree, N; Dinda, S et al. (1997) Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and antiestrogens in breast cancer cells. Oncogene 15:991-5
Hurd, C; Khattree, N; Alban, P et al. (1995) Hormonal regulation of the p53 tumor suppressor protein in T47D human breast carcinoma cell line. J Biol Chem 270:28507-10
D'souza, A; Hinduja, I N; Kodali, S et al. (1994) Interaction of newly synthesized antiprogesterone ZK98299 with progesterone receptor from human myometrium. Mol Cell Biochem 139:83-90
Haske, T; Nakao, M; Moudgil, V K (1994) Phosphorylation of immunopurified rat liver glucocorticoid receptor by the catalytic subunit of cAMP-dependent protein kinase. Mol Cell Biochem 132:163-71

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