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Biomedical subjects

S Wu

Publications and source records attributed to S Wu.

At least 451 records · Page 25Linked to original sources
PubMed1993

Characteristics of the eukaryotic initiation factor 2 associated 67-kDa polypeptide.

A eukaryotic initiation factor 2 (eIF-2) associated 67-kDa polypeptide (p67) protects the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation, and this promotes protein synthesis in the presence of active eIF-2 kinase(s), [Datta, B., et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 3324-3328]. This report presents the results of studies related to characteristics of p67 action and the mechanism of p67:eIF-2 interaction: (1) p67 antibodies inhibited protein synthesis in hemin-supplemented rabbit reticulocyte lysates, and such inhibition was reversed by preincubation of the antibodies, specifically with p67. (2) p67 inhibited HRI- and dsI-catalyzed phosphorylations of the eIF-2 alpha-subunit and histones, but it did not inhibit casein kinase catalyzed phosphorylation of the eIF-2 beta-subunit. (3) p67 bound specifically to the eIF-2 gamma-subunit. p67 co-immunoprecipitated with the eIF-2 subunits when a p67/eIF-2 mixture was treated with p67 or eIF-2 subunit antibodies and protein A agarose. However, when eIF-2 was preincubated specifically with the eIF-2 gamma-subunit antibodies, subsequent co-immunoprecipitation of p67 with the eIF-2 subunits was completely inhibited. Similarly, preincubation of p67 and p67 antibodies prevented subsequent p67 binding to eIF-2. Preincubation of eIF-2, with either eIF-2 alpha- or beta-subunit antibodies, had no effect on p67 co-immunoprecipitation with the eIF-2 subunits. (4) p67:eIF-2 interaction is necessary for p67 activity to protect the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Casein Kinases↗
PubMed1993

Tumor necrosis factor alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor alpha expression.

Ovarian tumor cells produce macrophage colony stimulating factor, a potent chemoattractant for monocytes. Monocytes and macrophages produce tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha or interleukin 1 beta (IL-1 beta) that can stimulate ovarian tumor cell growth. The present study has explored whether paracrine stimulation by monocyte derived cytokines might induce autocrine growth stimulation of normal and malignant ovarian epithelial cells. Endogenous expression of TNF-alpha mRNA was detected in ascites ovarian cancer cells isolated directly from patients, but not in established cultures of normal or malignant ovarian epithelial cells. When ascites tumor cells were cultured for 7 days, TNF-alpha expression ceased but could be reinduced by treatment with TNF-alpha or IL-1 beta. Ascites fluid contained concentrations of the cytokines that could mediate these effects. Similarly, treatment of normal or malignant ovarian epithelial cells with purified recombinant IL-1 beta or TNF-alpha induced transcription of TNF-alpha mRNA within 1 h. TNF-alpha protein could be detected by enzyme-linked immunosorbent assay in conditioned medium from IL-1 beta treated ovarian cancer cells. [3H]thymidine incorporation by normal or malignant ovarian epithelial cells was stimulated by a 24-h incubation with IL-1 beta or TNF-alpha. Stimulation of proliferation by IL-1 beta could be partially blocked by an antibody against TNF-alpha or by soluble TNF-alpha-receptor. Thus, TNF-alpha may function as both an autocrine and a paracrine growth factor in ovarian cancer.

Animals↗
PubMed1993

Use of bispecific heteroconjugated antibodies (anti-T cell antigen receptor x anti-MHC class II) to study activation of T cells with a full length or truncated antigen receptor zeta-chain.

Ligand-induced activation of T cells involves recognition of monovalent peptide Ag complexed with a cell surface MHC-encoded molecule. In contrast, antibody-induced activation of T cells typically requires external cross-linking of the TCR. To examine the mechanisms that underlie the ability of these different stimuli to signal, we have created bispecific chimeric antibody molecules (BA) that mimic Ag in several important aspects. Anti-TCR-alpha, -beta, or anti-CD3-epsilon Fab fragments were covalently coupled to an anti-MHC class II Fab fragment. These BA elicited IL-2 production or proliferation from Ag-specific T cell hybridoma cells or splenic T cells, respectively, in the presence, but not the absence, of accessory cells expressing the appropriate MHC class II molecule. This response was prevented by soluble blocking antibodies against the TCR or MHC class II. When "presented" by MHC class II-bearing accessory cells, anti-TCR x anti-MHC class II BA, like cell surface Ag, elicited IL-2 production from T cell transfectants expressing full length TCR zeta-chain but not from otherwise identical cells expressing truncated zeta; when immobilized on a plastic surface these BA were potent stimulators that induced equal amounts of IL-2 from the same cells. Purified Ag/MHC complexes immobilized on plastic were able to induce IL-2 production from T cells expressing the full length, but not the truncated, form of zeta. We hypothesize that TCR-mediated T cell activation requires stable aggregation of the TCR. In this model, activation by mobile cell surface Ag/MHC or BA occurs in two steps, occupancy-induced TCR clustering followed by stable aggregation facilitated by the presence of a full length zeta-chain. Immobilized high affinity anti-TCR antibodies, but not low affinity Ag/MHC complexes, directly promote stable receptor aggregates, and thus would not require a full length zeta-chain.

Animals↗
PubMed1993

Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor (NF-E2) to an enhancer element required for expression of an erythroid-specific gene.

Induction by hemin increases, while induction with 12-O-tetradecanoylphorbol-13-acetate (TPA) represses, erythroid-specific gene expression in the human cell line K562. We analyzed the effects of hemin or TPA induction on the binding and activity of transcription factors at a regulatory element found within the transcriptional regulatory sequences of many erythroid-specific genes. TPA induction increases the binding of ubiquitous AP-1 factors to this element. TPA induction inhibits the binding of the lineage limited transcription factor NF-E2 to this transcriptional control element. Hemin induction of K562 cells does not facilitate the binding of NF-E2 to its recognition site. Hemin induction appears to nonspecifically increase the expression of transiently transfected genes in K562 cells. Beyond this nonspecific increase in gene expression, hemin induction acts to increase the activity of the lineage limited transcription factor NF-E2. The divergent effects of hemin and TPA on gene expression in K562 cells are mediated, in part, by their contrasting effects on the transcription factor NF-E2.

Base Sequence↗
PubMed1993

Cell growth regulation in epithelial ovarian cancer.

BACKGROUND: As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes. METHODS: Recent articles and abstracts have been reviewed. RESULTS: The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor-alpha, (2) loss of autocrine growth inhibition by transforming growth factor-beta, (3) mutation or amplification of ras in 2-12% of cases, (4) amplification of myc in 23% of specimens, (5) expression of fms in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin-1, interleukin-6 and tumor necrosis factor, (7) overexpression of c-erbB-2 (HER-2/neu) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, fms, and HER-2/neu. Antibodies against the extracellular domain of the HER-2/neu gene product p185 inhibit the growth of tumor cells that overexpress HER-2/neu and are associated with marked decreases in diacylglycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin-mediated killing. Coexpression of HER-2/neu and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors. CONCLUSIONS: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER-2/neu gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy.

Carcinoma↗
PubMed1993

Conformation of complementarity determining region L1 loop in murine IgG lambda light chain extends the repertoire of canonical forms.

The refined structure of Se155-4 Fab fragment, the first murine antibody with the lambda light chain, reveals a novel conformation of the light chain complementarity determining region L1. This conformation extends the repertoire of canonical structures. The main determinant of this conformation is the packing of the Val27c side-chain into a hydrophobic pocket formed by the side-chains of Ala33, Leu66, Ala71 and Leu90. The framework L-FR3 loop, encompassing residues 66 to 72, which packs next to the L1 loop, bends significantly more toward the exterior of the molecule than in other Fab fragments. Sequence analysis suggests that the conformations of the L1 and L-FR3 loops observed in Se155-4 are adopted by a majority of murine lambda light chains.

Amino Acid Sequence↗
PubMed1993

Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post-transcriptional mechanisms.

Parathyroid hormone-related protein (PTHrP), a tumor product responsible for malignancy-associated hypercalcemia, is also produced in many normal tissues, including vascular smooth muscle cells (SMC). As PTHrP exhibits vasodilatory properties, we postulated that other vasoactive agents may control PTHrP gene expression in SMC. Addition of angiotensin II to serum-deprived SMC resulted in a marked induction of PTHrP mRNA by 2 h, with a peak (6-10-fold) at 4-6 h. Angiotensin II effects on PTHrP gene expression were inhibited by saralasin, an angiotensin II receptor antagonist, and blocked by actinomycin D and cycloheximide, suggesting a requirement for gene transcription and protein synthesis. Nuclear run-off assays revealed a 3-fold increase in PTHrP gene transcription 1 h after angiotensin II treatment. Angiotensin II also prolonged PTHrP mRNA half-life by 2-3-fold. Angiotensin-induced PTHrP mRNA is partially dependent on cyclooxygenase products and protein kinase C activation. Other vasoconstrictor substances, including serotonin and bradykinin, also stimulated PTHrP expression, whereas the vasodilator atrial natriuretic peptide did not. Addition of recombinant PTHrP-(1-141) significantly inhibited angiotensin II-induced SMC DNA synthesis. PTHrP expression is increased by angiotensin II through transcriptional and post-transcriptional mechanisms. In addition, PTHrP modulates the effect of angiotensin II on SMC proliferation. This suggests that PTHrP acts locally in SMC, possibly to oppose the vasoactive and/or growth-promoting effects of vasoconstrictor agents such as angiotensin II.

Angiotensin II↗
PubMed1993

Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two-domain protein with a calcium binding parallel beta roll motif.

The three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa, a zinc metalloprotease, has been solved to a resolution of 1.64 A by multiple isomorphous replacement and non-crystallographic symmetry averaging between different crystal forms. The molecule is elongated with overall dimensions of 90 x 35 x 25 A; it has two distinct structural domains. The N-terminal domain is the proteolytic domain; it has an overall tertiary fold and active site zinc ligation similar to that of astacin, a metalloprotease isolated from a European freshwater crayfish. The C-terminal domain consists of a 21-strand beta sandwich. Within this domain is a novel 'parallel beta roll' structure in which successive beta strands are wound in a right-handed spiral, and in which Ca2+ ions are bound within the turns between strands by a repeated GGXGXD sequence motif, a motif that is found in a diverse group of proteins secreted by Gram-negative bacteria.

Amino Acid Sequence↗
PubMed1993

Structure of Paramecium tetraurelia calmodulin at 1.8 A resolution.

The crystal structure of calmodulin (CaM; M(r) 16,700, 148 residues) from the ciliated protozoan Paramecium tetraurelia (PCaM) has been determined and refined using 1.8 A resolution area detector data. The crystals are triclinic, space group P1, a = 29.66, b = 53.79, c = 25.49 A, alpha = 92.84, beta = 97.02, and gamma = 88.54 degrees with one molecule in the unit cell. Crystals of the mammalian CaM (MCaM; Babu et al., 1988) and Drosophila CaM (DCaM; Taylor et al., 1991) also belong to the same space group with very similar cell dimensions. All three CaMs have 148 residues, but there are 17 sequence changes between PCaM and MCaM and 16 changes between PCaM and DCaM. The initial difference in the molecular orientation between the PCaM and MCaM crystals was approximately 7 degrees as determined by the rotation function. The reoriented Paramecium model was extensively refitted using omit maps and refined using XPLOR. The R-value for 11,458 reflections with F > 3 sigma is 0.21, and the model consists of protein atoms for residues 4-147, 4 calcium ions, and 71 solvent molecules. The root mean square (rms) deviations in the bond lengths and bond angles in the model from ideal values are 0.016 A and 3 degrees, respectively. The molecular orientation of the final PCaM model differs from MCaM by only 1.7 degrees. The overall Paramecium CaM structure is very similar to the other calmodulin structures with a seven-turn long central helix connecting the two terminal domains, each containing two Ca-binding EF-hand motifs. The rms deviation in the backbone N, Ca, C, and O atoms between PCaM and MCaM is 0.52 A and between PCaM and DCaM is 0.85 A. The long central helix regions differ, where the B-factors are also high, particularly in PCaM and MCaM. Unlike the MCaM structure, with one kink at D80 in the middle of the linker region, and the DCaM structure, with two kinks at K75 and I85, in our PCaM structure there are no kinks in the helix; the distortion appears to be more gradually distributed over the entire helical region, which is bent with an apparent radius of curvature of 74.5(2) A. The different distortions in the central helical region probably arise from its inherent mobility.

Amino Acid Sequence↗
PubMed1993

Crystal structure of the complex of human alpha-thrombin and nonhydrolyzable bifunctional inhibitors, hirutonin-2 and hirutonin-6.

The crystal structure of the complexes of hirutonin-2 and hirutonin-6 with human alpha-thrombin have been solved and refined to R-factors of 0.169 (2.0 A resolution) and 0.162 (2.1 A), respectively. Hirutonins belong to a family of bifunctional inhibitors bearing a noncleavable moiety mimicking the scissile bond. Hirutonin-2 is an analog of (D)Phe-Pro-Arg-Gly-hirudin49-65; hirutonin-6 has the same N-terminal tripeptide connected to a shortened fibrinogen exosite-binding part by a short, nonpeptidyl linker. The hirutonin-6 molecule is well defined in the electron density with the exception of the C-terminal Leu-h61. The linker follows near the bottom of the canyon connecting the active site with the exosite, forms a short antiparallel beta-sheet-like arrangement with Leu40-Leu41 and makes van der Waals contacts with Glu39-Leu40-Leu41 of thrombin. In the thrombin-hirutonin-2 complex, the N- and C-terminal parts of the inhibitor are well ordered (except the C-terminal Gln-h65) while the central portion of the linker is partially disordered. The glycine analog in the P1' position of hirutonin-2 assumes a conformation similar to that of the canonical form (Bode and Huber (1992) Eur. J. Biochem. 204:433-451) and supports the identification of the S1' site as restricted by His57, Trp60D, Lys60F, and the Cys42-Cys58 disulfide bridge. The carbonyl oxygen of the P1 arginine residue is located in the oxyanion hole formed by the NH groups of Gly193 and Ser195, while the carbonyl carbon is positioned within a short distance, 2.8 A, from the O gamma of Ser195. This resembles the conformation of the substrate-like inhibitors bound to other serine proteases. The N-terminal (D)Phe-Pro-Arg fragment common to both inhibitors binds to thrombin in a fashion very similar to that of other inhibitors having this motif. The binding of the C-terminus of hirutonins to the fibrinogen-binding exosite is similar to that observed in hirudin and hirulog complexes.

Amino Acid Sequence↗
PubMed1993

Establishment of National Quality Control Reference Panels and Requirements for Hepatitis B diagnosis reagents in China.

A National Quality Control Reference Panel for Hepatitis B Diagnostic Kits has been established. Markers for these standards which were prepared include National Standards for HBsAg and anti-HBs calibrated against WHO International Standards. In addition, Reference Panels for HBeAg, anti-HBe, anti-HBc, anti-HBc IgM and HBV were established and National Requirements set. These panels have been used for the nationwide evaluation of HB kits and for licensing purposes.

China↗
PubMed1993

The isolation of Cryptococcus neoformans from pigeon droppings and serotyping of naturally and clinically sourced isolates in China.

This is the first report on the isolation of Cryptococcus neoformans from pigeon droppings in China and their serotypes. C. neoformans colonies which produced brown colonies on caffeic acid-cornmeal agar were found in Twenty-five out of thirty-six samples of pigeon droppings. Fifty-one colonies randomly picked from the positive samples were identified as C. neoformans by a commercially available kit for carbon source assimilation test and Christensen's urea agar. Forty (78%) out of the 51 strains were serotyped as A and 11 (22%) as AD. At the same time, seventeen out of nineteen clinical isolates were serotyped as A and 2 as B. There are three findings in our results. One is that only C. neoformans var. neoformans strains could be isolated from pigeon droppings, although the variety gattii strains were found in the clinical isolates obtained in the same geographic site in China. The second is that serotype A strains were most frequently seen in natural and clinical materials in the southeast part of China, and serotype AD strains were isolated in pigeon droppings but not in clinical materials. The third is that the coexistence of serotype A and AD cells of C. neoformans strains in same samples of pigeon droppings were observed.

Animals↗
PubMed1993

Use of receptor antibodies to demonstrate membrane glucocorticoid receptor in cells from human leukemic patients.

Anti-peptide antibody to the human glucocorticoid receptor (GR) was produced and used to demonstrate that a subset of the GR population resides in the plasma membrane of human leukemic cells. Characterization of the antibody with intracellular GR (iGR) showed its ability to shift [3H]triamcinolone acetonide-labeled GR (4S protein) from two human leukemic cell lines to a higher density in sucrose gradients; Western and autoradiographic analysis of affinity-labeled ([3H]dexamethasone 21-mesylate) receptor revealed an immunoreactive and competitively labeled band of 94 kDa. CCRF-CEM cell membrane GR (mGR) resolved as a > 7S protein on density gradients and immunoselected cell surface protein labeled by whole cell biotinylation or affinity-labeling with [3H]dexamethasone 21-mesylate was approximately 145 kDa, demonstrating that mGR was larger in size than iGR, as has been shown previously for the mGR of mouse lymphoma cells. Analysis of mGR in lymphocytes of leukemic patients and the CCRF-CEM cell line indicated differences in levels of expression as shown by FACS and immunocytochemical analyses. We are currently using this system to study the correlation between the quantity of membrane-resident GRs and the glucocorticoid-induced lytic response, a relationship previously shown in the murine (S-49 cell) system.

Amino Acid Sequence↗
PubMed1993

Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants.

Genetic reassortment of the A/Shanghai/11/87 (H3N2) variant of influenza A virus with A/PR8/34 (H1N1) virus [the standard donor of high yield (hy) genes for influenza vaccine viruses] resulted in the isolation of two reassortants with differing H3 haemagglutinin (HA) phenotypes, X-99 and X-99a. The two HA phenotypes were derived from individual subpopulations of the H3N2 wild-type virus during the reassortment event. The HA mutants and their respectively derived reassortants (identical in RNA genotype) differed in antigenicity, replication characteristics, yield in chick embryos and haemagglutinin gene sequence. Despite antigenic differences in reactions to polyclonal rabbit antisera of 60%, both X-99 and X-99a, the hy reassortants, were equally immunogenic and protective in BALB/c mice to challenge by parental wild-type virus. Differences in HA phenotype were related to a Ser to Ile change at amino acid position 186. These findings emphasize the polymorphism of influenza virus strains as well as the need for caution in selection of vaccine strains from among antigenically distinct viral subpopulations.

Amino Acid Sequence↗
PubMed1993

Retroposition in a family of carcinoma-associated antigen genes.

The gene encoding the carcinoma-associated antigen defined by the monoclonal antibody GA733 is a member of a family of at least two type I membrane proteins. This study describes the mechanism of evolution of the GA733-1 and GA733-2 genes. A full-length cDNA clone for GA733-1 was obtained by screening a human placental library with a genomic DNA probe. Comparative analysis of the cDNA sequence with the previously determined genomic sequence confirmed that GA733-1 is an intronless gene. The GA733-2 gene encoding the monoclonal antibody-defined antigen was molecularly cloned with a cDNA probe and partially sequenced. Comparison of GA733-2 gene sequences with the previously established cDNA sequence revealed that this gene consists of nine exons. The putative promoter regions of the GA733-1 and GA733-2 genes are unrelated. These findings suggest that the GA733-1 gene was formed by the retroposition of the GA733-2 gene via an mRNA intermediate. Prior to retroposition, the GA733-2 gene had been affected by exon shuffling. Analysis of GA733-2 exons revealed that many delineate structural motifs. The GA733-1 retroposon was localized either to chromosome region 1p32-1p31 or to 1p13-1q12, and the GA733-2 founder gene was localized to chromosome 4q.

Amino Acid Sequence↗
PubMed1993

Effects of N-terminal, midregion, and C-terminal parathyroid hormone-related peptides on adenosine 3',5'-monophosphate and cytoplasmic free calcium in rat aortic smooth muscle cells and UMR-106 osteoblast-like cells.

N-Terminal analogs of PTH-related protein (PTHrP) and PTH bind to a common receptor and exhibit similar biological properties. However, recent studies suggest that certain midregion and C-terminal PTHrP peptides have activities distinct from those of PTH in the placenta and in osteoclasts, respectively. In this study we determined the biological activities of full-length recombinant PTHrP-(1-141) and several synthetic N-terminal, midregion, and C-terminal PTHrP fragments in two PTHrP-producing cell types. Peptides were tested for their ability to stimulate cAMP production and raise intracellular free calcium ([Ca2+]i) in primary rat aortic smooth muscle cells (VSMC) and UMR-106 rat osteoblast-like (UMR) cells. In UMR cells PTHrP-(1-34)NH2, PTHrP-(1-141), and bovine PTH-(1-34) all increased cAMP (approximately 50 fold) and [Ca2+]i (180 nM). By contrast, in VSMC, these N-terminal peptides increased cAMP (3-fold) but had no detectable effect on [Ca2+]i. PTHrP-(1-34) and PTHrP-(1-141) significantly blunted the angiotensin II-induced rise in cAMP (but not the calcium signal) consistent with the concept that PTHrP opposes angiotensin II activity in VSMC. PTHrP-(67-86)NH2, PTHrP-(107-138)NH2, and PTHrP-(107-111)NH2 had no effect on either cAMP or [Ca2+]i in either cell type. VSMC and UMR-106 cells both expressed a 2.5-kilobase PTH/PTHrP receptor messenger RNA (mRNA) transcript. However, high affinity specific binding of 125I-labeled [Tyr36] PTHrP-(1-36)NH2 was detected in UMR cells but not in VSMC. We conclude that the PTH-like, N terminus of the PTHrP molecule is critical in induction of cAMP and [Ca2+]i pathways in UMR cells, and for cAMP stimulation in VSMC. In addition, PTHrP, like other established vasodilators, signals in VSMC mainly (if not exclusively) by increasing the production of cAMP.

Animals↗
PubMed1993

Regulation of atrial natriuretic peptide, thromboxane and prostaglandin production by androgen in elderly men with coronary heart disease.

Several recent observations suggest that atrial natriuretic peptides (ANP) can modulate steroidogenesis in isolated rat Leydig cells and in young men. Other observations suggest that catechol estrogen can inhibit prostaglandin (PGI2) release in the endothelium, and we had found that androgen can relieve angina pectoris and improve myocardial ischemia in elderly men with coronary heart disease (CHD), possibly through relieving coronary artery smooth muscle spasm. Because ANP and PGI2 are vasoactive peptides which regulate vasomotion, there must be an interaction between steroidogenesis hormones and vasoactive peptides. We evaluated the effects of androgen (Sustanon 250) administration on plasma ANP, PGI2 and thromboxane (TXA2) levels in elderly men with CHD. Thirty 60-75-year-old men with CHD received 250 mg (1 ml) Sustanon 250 injection, and 30 age- and sex-matched CHD patients received 1 ml saline. Plasma ANP, PGI2, TXA2, estradiol (E2) and testosterone (T) were determined before injection and 3 weeks thereafter. The results showed that Sustanon 250 administration increased plasma ANP levels, decreased TXA2 and increased PGI2 levels significantly, and thereby improved the TXA2/PGI2 imbalance in CHD patients (all P < 0.01). Meanwhile, serum T levels rose (P < 0.01), but E2 levels remained unchanged, and thus the E2/T ratio decreased (P < 0.05). Our findings demonstrate that androgen exerts its regulatory role by altering plasma ANP levels and the TXA2/PGI2 ratio.

6-Ketoprostaglandin F1 alpha↗