Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sex steroid binding capacity was investigated in malignant cells from 32 patients with acute non-lymphoblastic leukemia (25 patients with acute myeloid leukemia, 4 with subacute leukemia, 3 with chronic myeloid leukemia in blast crisis) and 30 patients with acute lymphoblastic leukemia. Specific binding of labelled steroids was characterized either by competition assay in cytosol fraction or by whole-cell incorporation. In some cases further characterization of the receptor complex was attempted by sucrose gradient centrifugation and gel filtration column. The results show the presence of specific binding sites for dexamethasone (22/32 in non ALL and 30/30 in ALL), for estrogens (11/15 in non-ALL and 5/12 in ALL), for progestins (8/25 in non-ALL and 5/13 in ALL) for androgens when R1881 was used as ligand (8/21 in non-ALL and 5/10 in ALL patients) but only 1/13 non-ALL patients and no ALL patients when labelled 5 alpha DHT was used. These results indicate that the blast cells from patients with acute leukemia contain specific proteins binding steroids with a high affinity. Our results for dexamethasone receptors are similar to those described in the literature in ALL and non-ALL.
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PMID:Androgen, estrogen and progestin binding sites in human leukemic cells. 694 98

Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at -106/-91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors.
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PMID:Androgen receptor repression of GnRH gene transcription. 2207 52