Recent progress in hormone research最新文献

{"title":"Regulation of a distinctive set of genes in glucocorticoid-evoked apoptosis in CEM human lymphoid cells.","authors":"E Brad Thompson,&nbsp;Betty H Johnson","doi":"10.1210/rp.58.1.175","DOIUrl":"https://doi.org/10.1210/rp.58.1.175","url":null,"abstract":"<p><p>Gene expression was evaluated in clones of the acute lymphoblastic leukemic cell line CEM that were sensitive or resistant to apoptosis evoked by the glucocorticoid, dexamethasone (Dex). Founding clones CEM-C7 (glucocorticoid sensitive) and CEM-C1 (glucocorticoid resistant) were subcloned to maximize uniformity of each population studied. Among subclones of C1, our original pseudodiploid clone of glucocorticoid-resistant cells, we found a high proportion of hyperploid clones. Most C1 subclones were glucocorticoid resistant but two C1 subclones were found to be revertants to glucocorticoid sensitivity. Glucocorticoid receptor content of the C1 subclones varied almost 5-fold but higher quantity of receptors did not guarantee steroid sensitivity. Gene expression analysis was carried out on microchips containing representations for approximately 12,600 human genes. When a group of four subclones from C1 (three glucocorticoid-resistant and one glucocorticoid-sensitive revertant) were compared with the glucocorticoid-sensitive subclone CEM-C7-14 for basal gene expression, the four C1 subclones clustered closely and far from C7-14. Thus, basal gene expression in the C1 subclones differed for a large number of genes from that in the C7 subclone. Reversion to glucocorticoid sensitivity did not cause a major shift in basal gene expression to a more C7-like state. Three clones (one revertant glucocorticoid sensitive from C1 subclone, one C7 sensitive subclone, and one C1 glucocorticoid-resistant subclone) were compared for the genes regulated by treatment for 20 hours with 10(-6)M Dex. This interval brings the cells to a point just before the onset of apoptosis. We tested the hypothesis that a distinctive set of genes would be regulated in the glucocorticoid-sensitive clones. This proved to be so. In three experiments, at our chosen levels of discrimination, 39 genes were consistently induced > or = 2.5-fold and 21 genes were consistently reduced > or = 2-fold in glucocorticoid-sensitive clones but not in the glucocorticoid-resistant clone. The glucocorticoid-resistant clone showed induction or reduction of 88 genes different from those regulated in the glucocorticoid-sensitive clones. These data support our hypothesis and further show that the glucocorticoid-resistant clone is capable of responding to steroid but with a different set of genes. We propose that a general metabolic switch accounts for the alteration.</p>","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"58 ","pages":"175-97"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22426615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paired-like repression/activation in pituitary development.","authors":"Lorin E Olson,&nbsp;Jeremy S Dasen,&nbsp;Bong Gun Ju,&nbsp;Jessica Tollkuhn,&nbsp;Michael G Rosenfeld","doi":"10.1210/rp.58.1.249","DOIUrl":"https://doi.org/10.1210/rp.58.1.249","url":null,"abstract":"<p><p>Pituitary gland development is controlled by signals that guide expression of specific combinations of transcription factors that dictate serial determination and differentiation events. One class of factors is paired-like homeodomain factors. Two that have been investigated are the repressor Hex1/Rpx and activator prophet of Pit-1 (Prop-1), which exert selective roles during pituitary development. The opposing actions of these factors provide one aspect of pituitary organogenesis.</p>","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"58 ","pages":"249-61"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22426618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic analysis of glucocorticoid-regulated promoters in murine T-lymphoma cells.","authors":"Lu Chen,&nbsp;Celeste Finnerty,&nbsp;William C Gustafson,&nbsp;Craig R Bush,&nbsp;Ping Chi,&nbsp;Huiping Guo,&nbsp;Bruce Luxon,&nbsp;Alan P Fields,&nbsp;E Aubrey Thompson","doi":"10.1210/rp.58.1.155","DOIUrl":"https://doi.org/10.1210/rp.58.1.155","url":null,"abstract":"<p><p>We have undertaken a high-throughput analysis to identify targets of glucocorticoid regulation in P1798 murine T-lymphoma cells. G1/S-arrested cultures were treated for 8 hours with 0.1 microM dexamethasone (dex) in the presence and absence of 1 microg/ml cycloheximide. Untreated cultures and cultures exposed to cycloheximide alone were prepared as controls. RNA was isolated and gene expression analyzed using Affymetrix MG-U74A oligonucleotide arrays (Gene Chips). Three independent experiments were performed. The data were analyzed using a variety of statistical and analytical approaches in order to identify primary transcriptional targets of the glucocorticoid receptor. We identified 44 genes that increase by > 2-fold in both dex-treated and dex + cycloheximide-treated cultures (relative to control and cycloheximide-treated cultures) in three replicate experiments. Statistical analysis of control data indicate that the probability that a given probeset would, as a result of random error, increase > 2-fold both in the presence and absence of cycloheximide in two independent experiments is approximately 7 x 10(-9). We have retrieved from the Celera mouse genomic sequence 8 kb of promoter sequence, spanning 4 kb either side of the 5'-end of the cDNA from eight of the induced genes. These sequences were analyzed for potential glucocorticoid receptor binding sites. Five of these genes contain the sequence ACAnnnTGTnCT within 4 kb of the presumptive transcriptional start site. Eight control genes were selected at random and analyzed for the sequence ACAnnnTGTnCT. Two control genes had such sequences within 4 kb of the transcriptional start site.</p>","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"58 ","pages":"155-74"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22426614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical approach to DNA chip analysis.","authors":"N M Svrakic,&nbsp;O Nesic,&nbsp;M R K Dasu,&nbsp;D Herndon,&nbsp;J R Perez-Polo","doi":"10.1210/rp.58.1.75","DOIUrl":"https://doi.org/10.1210/rp.58.1.75","url":null,"abstract":"<p><p>Statistical methods for analyzing data from DNA microarray experiments are reviewed. Specifically, we discuss common experimental setups, methods for data reduction and clustering, and analysis of time-course experiments. While early microarray studies focused mainly on the basic methodological and technical aspects of DNA arrays, emphasis has shifted to biological, medical, and clinical applications. We mention several of these and present results from our recent research as illustrative examples. New developments in this ever-growing field are outlined.</p>","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"58 ","pages":"75-93"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22427276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology.","authors":"Rachel J Mann,&nbsp;Ruth A Keri,&nbsp;John H Nilson","doi":"10.1210/rp.58.1.343","DOIUrl":"https://doi.org/10.1210/rp.58.1.343","url":null,"abstract":"<p><p>Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful transgenic mouse model.</p>","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"58 ","pages":"343-75"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22427757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular defects of the androgen receptor.","authors":"M. McPhaul","doi":"10.1210/RP.57.1.181","DOIUrl":"https://doi.org/10.1210/RP.57.1.181","url":null,"abstract":"Mutations in the androgen receptor (AR) gene cause a range of phenotypic abnormalities of male sexual development. At one end of the spectrum are individuals with complete androgen insensitivity (complete testicular feminization) who exhibit normal breast development and female external genitalia. At the other extreme are individuals with male phenotypes that are characterized by either subtle undervirilization or infertility. Studies in a number of different laboratories have identified mutations of the AR gene in subjects with androgen resistance syndromes. Defects that interrupt the AR open-reading frame have been traced to a number of distinct types of genetic alterations, have been identified in widely separated segments of the AR gene, and are invariably associated with the phenotype of complete androgen insensitivity. By contrast, mutations that cause single amino acid substitutions within the AR are localized to the DNA- or ligand-binding domains of the receptor protein and have been associated with the full range of androgen-resistant phenotypes. Regardless of the nature of the mutation, functional studies and assays of AR abundance suggest that the phenotypic abnormalities that result from mutation of the AR are the result of the impairment of receptor function, decreases in receptor concentration, or both.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"38 1","pages":"181-94"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72664158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factors underlying the development and endocrine functions of the placenta.","authors":"J. Cross, L. Anson-Cartwright, I. Scott","doi":"10.1210/RP.57.1.221","DOIUrl":"https://doi.org/10.1210/RP.57.1.221","url":null,"abstract":"The placenta has been the subject of extensive basic research efforts in two distinct fields. The developmental biology of placenta has been studied because it is the first organ to develop during embryogenesis and because a number of different gene mutations in mice result in embryonic lethality due to placental defects. The trophoblast cell lineage is relatively simple such that only two major, terminally differentiated cell types appear: an \"invasive trophoblast\" cell subtype such as extravillous cytotrophoblast cells in humans and trophoblast giant cells in mice, and a \"transport trophoblast\" cell subtype that is a syncytium (syncytiotrophoblast) in humans and mice. These two cell types also have been the focus of endocrinologists because they are the source of major placental hormones. Understanding the transcriptional regulation of placental hormone genes has given insights into the control of specificity of gene expression. Because most placental hormones are produced by very specific trophoblast cell subtypes, the transcriptional details promise to give insights into cell-subtype specification. The fields of developmental biology and molecular endocrinology appear to be meeting on this common ground with the recent discovery of key transcription factors. Specifically, the basic helix-loop-helix (bHLH) transcription factor Hand1 is essential for differentiation of trophoblast giant cells in mice and also regulates the promoter for the giant cell-specific hormone, placental lactogen I gene (Pl1). In contrast, formation of syncytiotrophoblast cells in mice is controlled by a distinct genetic pathway that is governed by the Gcm1 transcription factor, a homologue of the Drosophila glial cells missing gene. Human GCM I has been shown to regulate the activity of the placental-specific enhancer of the aromatase gene (CYP19), which is specifically expressed in syncytiotrophoblast. Together, these findings imply that some key transcription factors have the dual functions of controlling both critical cell fate decisions in the trophoblast cell lineage and later the transcription of cell subtype-specific genes unrelated to development.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"337 1","pages":"221-34"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76582204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the mitotic and meiotic cell cycles in the male germ line.","authors":"D. Wolgemuth, Erika Laurion, Karen M. Lele","doi":"10.1210/RP.57.1.75","DOIUrl":"https://doi.org/10.1210/RP.57.1.75","url":null,"abstract":"Mammalian gametogenesis provides a unique system in which to study cell-cycle regulation. Furthermore, understanding the genetic program controlling the mitotic and meiotic divisions of the germ line will provide insight into understanding infertility and new directions for contraception. Male and female germ cells have stages of cell-cycle regulation in common, including a mitotic proliferative stage, entry into meiosis, completion of a reductive division, and entry into a quiescent state awaiting signals at fertilization. However, the timing of these events - and, indeed, even the stage of development at which these events occurs - differs in the two sexes. The genes involved in controlling these specialized mitotic and meiotic cycles of mammalian germ cell differentiation are only now being identified. They include a complex array of kinases, phosphatases, regulatory proteins (e.g., cyclins), and an equally complex array of substrates, including components of the nuclear and cytoplasmic structures involved in cell division. This chapter provides an overview of our current understanding of cell-cycle regulation in mammalian mitotic cells and the importance of restriction points. A summary of observations regarding the expression of various cell-cycle regulatory genes in mouse gametes is provided, along with comments on interesting differences between mitotic and meiotic cells. Finally, the role of the novel A-type cyclin, cyclin A1, during male meiosis is discussed in depth.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"7 1","pages":"75-101"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82575574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anabolic steroids.","authors":"C. Kuhn","doi":"10.1210/rp.57.1.411","DOIUrl":"https://doi.org/10.1210/rp.57.1.411","url":null,"abstract":"The term \"anabolic steroids\" refers to testosterone derivatives that are used either clinically or by athletes for their anabolic properties. However, scientists have questioned the anabolic effects of testosterone and its derivatives in normal men for decades. Most scientists concluded that anabolic steroids do not increase muscle size or strength in people with normal gonadal function and have discounted positive results as unduly influenced by positive expectations of athletes, inferior experimental design, or poor data analysis. There has been a tremendous disconnect between the conviction of athletes that these drugs are effective and the conviction of scientists that they aren't. In part, this disconnect results from the completely different dose regimens used by scientists to document the correction of deficiency states and by athletes striving to optimize athletic performance. Recently, careful scientific study of suprapharmacologic doses in clinical settings - including aging, human immunodeficiency virus, and other disease states - supports the efficacy of these regimens. However, the mechanism by which these doses act remains unclear. \"Anabolism\" is defined as any state in which nitrogen is differentially retained in lean body mass, either through stimulation of protein synthesis and/or decreased breakdown of protein anywhere in the body. Testosterone, the main gonadal steroid in males, has marked anabolic effects in addition to its effects on reproduction that are easily observed in developing boys and when hypogonadal men receive testosterone as replacement therapy. However, its efficacy in normal men, as during its use in athletes or in clinical situations in which men are eugonadal, has been debated. A growing literature suggests that use of suprapharmacologic doses can, indeed, be anabolic in certain situations; however, the clear identification of these situations and the mechanism by which anabolic effects occur are unclear. Furthermore, the pharmacology of \"anabolism\" is in its infancy: no drugs currently available are \"purely\" anabolic but all possess androgenic properties as well. The present review briefly recapitulates the historic literature about the androgenic/anabolic steroids and describes literature supporting the anabolic activity of these drugs in normal people, focusing on the use of suprapharmacologic doses by athletes and clinicians to achieve anabolic effects in normal humans. We will present the emerging literature that is beginning to explore more specific mechanisms that might mediate the effects of suprapharmacologic regimens. The terms anabolic/androgenic steroids will be used throughout to reflect the combined actions of all drugs that are currently available.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"20 1","pages":"411-34"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88848249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolactin modulation of immune and inflammatory responses.","authors":"L. Yu-Lee","doi":"10.1210/RP.57.1.435","DOIUrl":"https://doi.org/10.1210/RP.57.1.435","url":null,"abstract":"Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"67 1","pages":"435-55"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83508699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}