Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A protein has been identified that reconstitutes the 4.5S androgen receptor to the classical 8S form on sucrose gradients of low ionic strength (25 mM KCl and 50 mM Tris). Rat prostate Dunning tumor (R3327) cytosol labeled with [3H]dihydrotestosterone was chromatographed on phosphocellulose to separate the 4.5S receptor from this protein, which we refer to as 8S androgen receptor-promoting factor. The 8S promoting factor has the following physiocochemical properties: heat labile (60 C; 30 min), Stokes radius of 58 degrees A, molecular weight of 170,000 or more, precipitates in 40% saturated (NH4)2SO4, elutes from DEAE-Sepharose in 0.1 M KCl, and elutes from phosphocellulose in 0.1 M KCl. The reconstituted 8S receptor complex is similar to the native 8S receptor in that it is labile to heat and physiological salt concentrations, has a Stokes radius of 91 degrees A, and has a molecular weight of approximately 326,000. The 8S promoting factor is present in mature male rat serum, but is undetectable in sera of male rats 16 days of age or younger. The factor appears to be produced by androgen-responsive cells, since it was found in all tissues of the 15-day-old male rat known to contain androgen receptor. Spleen was found to lack both the 8S promoting factor and the androgen receptor. The 8S promoting factor was detected in serum of female rats and in hypophysectomized (44 days) or castrated (2 or 4 weeks) mature male rats. Salt extracts of purified nuclei from the androgen-dependent Dunning tumor also contain the factor. It is suggested that a specific interaction between the two intracellular proteins, 8S androgen receptor-promoting factor and the androgen receptor, may modulate the androgen responsiveness of target cells.
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PMID:Identification of an 8S androgen receptor-promoting factor that converts the 4.5S form of the androgen receptor to 8S. 725 51

There is a concern that certain industrial chemicals found in the environment may mimic or antagonize endogenous hormones and adversely affect the endocrine as well as the immune system. The objective of this study was to determine if exposure of Crl:CD (SD)BR male rats to 17beta-estradiol (17beta-E2), an estrogen receptor agonist, or flutamide (FLUT), an androgen receptor antagonist, would significantly alter the primary IgM humoral immune response to sheep red blood cells (SRBC). This study was conducted in the context of a male in vivo Tier I battery designed to identify endocrine-active compounds (EACs). The Tier I male battery consists of organ weights coupled with a comprehensive hormonal assessment. Rats were dosed by the intraperitoneal route for 15 days with vehicle or 0.001, 0.0025, 0.0075, or 0.050 mg/kg/day 17beta-E2 or 0.25, 1, 5, or 20 mg/kg/day FLUT. Six days prior to termination, selected rats were injected intravenously with SRBC for assessment of humoral immune function. Spleen cell number and spleen and thymus weights were obtained. Serum was analyzed for anti-SRBC IgM antibody by using an enzyme-linked immunosorbent assay. At 0.050 mg/kg/day 17beta-E2, mean final body and absolute thymus weights were significantly decreased to 84 and 65% of control, respectively. 17beta-E2 did not significantly alter spleen weight, spleen cell number, or the primary IgM humoral immune response to SRBC. The no-observed-adverse-effect level (NOAEL) for immune system alteration was 0.050 mg/kg/day 17beta-E2 since the decrease in absolute thymus weight was judged to be secondary to the decrements in body weight. In the Tier I male battery, responses to 17beta-E2 included decreased absolute testis and epididymis weights, decreased relative accessory sex gland unit weights, hormonal alterations (decreased serum testosterone (T), dihydrotestosterone (DHT), and luteinizing hormone (LH), and increased serum prolactin and E2 levels). The lowest-observed-adverse-effect level (LOAEL) for the reproductive indices was 0.001 mg/kg/day 17beta-E2 based on the hormonal alterations seen at this level; no NOAEL was established. Exposure to FLUT did not significantly alter mean final body, spleen, or absolute thymus weights, spleen cell number, or the primary IgM humoral immune response to SRBC. A significant increase (118% of control) in relative thymus weight was observed at 20 mg/kg/day FLUT. The NOAEL for immune system alteration was 5 mg/kg/day FLUT based on the increased relative thymus weights that were judged to be compound-related. In the Tier I male battery, responses to FLUT included decreased absolute epididymis and relative accessory sex gland unit weights and hormonal alterations (increased serum T, DHT, E2, and LH, and decreased follicle stimulating hormone levels). The LOAEL for the reproductive indices was 0.25 mg/kg/day FLUT based on the hormonal alterations seen at this level; no NOAEL was established. Based on these data, the reproductive and not the immune system appears to be the primary target organ of toxicity in young adult male rats treated with either 17beta-E2 or FLUT.
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PMID:Evaluation of the primary humoral immune response following exposure of male rats to 17beta-estradiol or flutamide for 15 days. 992 70

The production of B lymphocytes is regulated in part by physiologic levels of androgens and estrogens. While these sex hormones down-regulate B lymphopoiesis, augmentation of B lymphopoiesis occurs under conditions where androgen or estrogen levels are decreased. In this study we examine the effect of androgen ablation of male mice on B lymphopoiesis and on the phenotypic composition of peripheral B lymphocyte populations. Spleen and thymic weights are significantly increased following castration, as is the total number of peripheral blood lymphocytes. However, the absolute numbers of B cells in the periphery are selectively increased following castration; the numbers of T cells, NK cells and granulocytes remain unchanged. The increase in circulating B cells is due largely to increases in the numbers of recent bone marrow emigrants expressing a B220(lo+)CD24(hi+) phenotype and these cells remain significantly elevated in castrated mice for up to 54 days post-castration. Similar increases in the percentages of newly emigrated B cells are observed in mice that lack a functional androgen receptor (TFM:). Finally, assessments of B cell progenitors in the bone marrow revealed significant increases in the relative numbers of IL-7-responsive B cell progenitors, including cells in Hardy fractions B (early pro-B cells), C (late pro-B cells), D (pre-B cells) and E (immature B cells). These findings demonstrate that androgen ablation following castration significantly and selectively alters the composition of peripheral B cells in mice. Further, these alterations result from the potentiating effects of androgen ablation on IL-7-responsive pro-B cell progenitors.
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PMID:Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. 1128 94