Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells
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{"title"=>"Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Julie", "last_name"=>"Guillermet-Guibert", "scopus_author_id"=>"8847067100"}, {"first_name"=>"Lee B.", "last_name"=>"Smith", "scopus_author_id"=>"7410392470"}, {"first_name"=>"Guillaume", "last_name"=>"Halet", "scopus_author_id"=>"6602299668"}, {"first_name"=>"Maria A.", "last_name"=>"Whitehead", "scopus_author_id"=>"55196070400"}, {"first_name"=>"Wayne", "last_name"=>"Pearce", "scopus_author_id"=>"8528934800"}, {"first_name"=>"Diane", "last_name"=>"Rebourcet", "scopus_author_id"=>"36022891000"}, {"first_name"=>"Kelly", "last_name"=>"León", "scopus_author_id"=>"55153913900"}, {"first_name"=>"Pascale", "last_name"=>"Crépieux", "scopus_author_id"=>"6602584880"}, {"first_name"=>"Gemma", "last_name"=>"Nock", "scopus_author_id"=>"16432470000"}, {"first_name"=>"Maria", "last_name"=>"Strömstedt", "scopus_author_id"=>"56767954700"}, {"first_name"=>"Malin", "last_name"=>"Enerback", "scopus_author_id"=>"56066422300"}, {"first_name"=>"Claude", "last_name"=>"Chelala", "scopus_author_id"=>"24075502900"}, {"first_name"=>"Mariona", "last_name"=>"Graupera", "scopus_author_id"=>"55950922800"}, {"first_name"=>"John", "last_name"=>"Carroll", "scopus_author_id"=>"35567366700"}, {"first_name"=>"Sabina", "last_name"=>"Cosulich", "scopus_author_id"=>"6602480771"}, {"first_name"=>"Philippa T.K.", "last_name"=>"Saunders", "scopus_author_id"=>"35516023700"}, {"first_name"=>"Ilpo", "last_name"=>"Huhtaniemi", "scopus_author_id"=>"7102262318"}, {"first_name"=>"Bart", "last_name"=>"Vanhaesebroeck", "scopus_author_id"=>"7004331309"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"84938769267", "doi"=>"10.1371/journal.pgen.1005304", "issn"=>"15537404", "pui"=>"605567831", "pmid"=>"26132308", "scopus"=>"2-s2.0-84938769267"}, "id"=>"06fdb565-02df-34c6-9663-b75817be685e", "abstract"=>"The organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact.", "link"=>"http://www.mendeley.com/research/novel-role-p110%CE%B2-pi-3kinase-male-fertility-through-regulation-androgen-receptor-activity-sertoli-cel", "reader_count"=>13, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Iran"=>1, "United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2159116"], "description"=>"<p><b>A</b>) mRNA expression of stem cell markers in testes of adult mice of the indicated genotypes as determined by RT-qPCR and normalized with 18S expression and corrected for total testis weight (n = 5). Student's t-test: ***, p<0.001. <b>B</b>) Western blot analysis of c-kit expression in adult testes of mice with the indicated genotypes (n = 4). Arrows point to the 100 kDa and 150 kDa forms of c-kit. <b>C</b>) Immunofluorescence using anti-c-kit TRITC-labeled antibodies in adult WT and p110β<sup>D931A/D931A</sup> testes (n = 3). Scale: 20 μm. * c-kit-positive germ cells; # c-kit-positive Leydig cells. <b>D</b>) Breeding efficiency of p110α<sup>D933A/WT</sup> males crossed with 2 WT females over a 4 month period (C57BL/6 background). Unpaired t-test: **, p<0.01. <b>E</b>) Weight of reproductive organs in P35 (n>3) and adult 12-week-old WT and p110α<sup>D933A/WT</sup> mice (n>6). Mann-Whitney: *, p<0.05. <b>F</b>) H&E staining of testes of D35 and adult WT and p110α<sup>D933A/WT</sup> mice (n>3). Scale: 20 μm. <b>G</b>) A schematic representation of the roles of p110α and p110β in the regulation of male fertility.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471104, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g006", "stats"=>{"downloads"=>3, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_p110_945_couples_to_c_kit_in_testes_and_regulates_male_fertility_/1471104", "title"=>"p110α couples to c-kit in testes and regulates male fertility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159153", "https://ndownloader.figshare.com/files/2159154", "https://ndownloader.figshare.com/files/2159155", "https://ndownloader.figshare.com/files/2159156", "https://ndownloader.figshare.com/files/2159157", "https://ndownloader.figshare.com/files/2159158", "https://ndownloader.figshare.com/files/2159159", "https://ndownloader.figshare.com/files/2159160", "https://ndownloader.figshare.com/files/2159161", "https://ndownloader.figshare.com/files/2159163", "https://ndownloader.figshare.com/files/2159164", "https://ndownloader.figshare.com/files/2159165", "https://ndownloader.figshare.com/files/2159166", "https://ndownloader.figshare.com/files/2159167", "https://ndownloader.figshare.com/files/2159168", "https://ndownloader.figshare.com/files/2159169", "https://ndownloader.figshare.com/files/2159170"], "description"=>"<div><p>The organismal roles of the ubiquitously expressed class I PI3Kisoform p110β remain largely unknown. Using a new kinase-deadknockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene <i>Rhox5</i>, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact.</p></div>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471139, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005304.s001", "https://dx.doi.org/10.1371/journal.pgen.1005304.s002", "https://dx.doi.org/10.1371/journal.pgen.1005304.s003", "https://dx.doi.org/10.1371/journal.pgen.1005304.s004", "https://dx.doi.org/10.1371/journal.pgen.1005304.s005", "https://dx.doi.org/10.1371/journal.pgen.1005304.s006", "https://dx.doi.org/10.1371/journal.pgen.1005304.s007", "https://dx.doi.org/10.1371/journal.pgen.1005304.s008", "https://dx.doi.org/10.1371/journal.pgen.1005304.s009", "https://dx.doi.org/10.1371/journal.pgen.1005304.s010", "https://dx.doi.org/10.1371/journal.pgen.1005304.s011", "https://dx.doi.org/10.1371/journal.pgen.1005304.s012", "https://dx.doi.org/10.1371/journal.pgen.1005304.s013", "https://dx.doi.org/10.1371/journal.pgen.1005304.s014", "https://dx.doi.org/10.1371/journal.pgen.1005304.s015", "https://dx.doi.org/10.1371/journal.pgen.1005304.s016", "https://dx.doi.org/10.1371/journal.pgen.1005304.s017"], "stats"=>{"downloads"=>45, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Novel_Role_for_p110_946_PI_3_Kinase_in_Male_Fertility_through_Regulation_of_Androgen_Receptor_Activity_in_Sertoli_Cells_/1471139", "title"=>"Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159089"], "description"=>"<p><b>A</b>) Weight of organs in 12-week-old mice (n = 4). <b>B</b>) Mice with the indicated genotype were bred for a 6-month period (cages of 2 females with 1 male; > 3 couples) and the average number of litters per month was assessed. Mann-Whitney: **, p<0.01. <b>C</b>) Average size of litters obtained from breeding pairs (2 females with one male for ≥4 months). Unpaired t-test: *, p<0.05; **, p<0.01.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471097, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g001", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_p110_946_kinase_activity_positively_regulates_female_and_male_fertility_/1471097", "title"=>"p110β kinase activity positively regulates female and male fertility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159091"], "description"=>"<p><b>A</b>) Females of the indicated genotype were crossed with WT males (n = 5 females crossed with 2 different males). The percentage of ovulations which became implanted embryos (left panel) was calculated as follows: [numbers of implanted E13.5 embryos + number of resorptions]/corpus luteum numbers in the ovaries (indicative of the number of ovulated oocytes)] x 100 (right panel). Mann-Whitney: *, p<0.05. <b>B</b>) Females of the indicated genotype were superovulated and mated with a p110β<sup><b>D931A/WT</b></sup> male. Two-cell embryos were recovered from the oviducts and cultured <i>in vitro</i> for 4 days, at which time embryos were scored for development to the morula/blastocyst stage or any earlier developmental stage, and genotyped. Mann-Whitney: *, p<0.05.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471099, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Maternal_and_embryonic_p110_946_kinase_activity_regulate_preimplantation_embryogenesis_/1471099", "title"=>"Maternal and embryonic p110β kinase activity regulate preimplantation embryogenesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159092"], "description"=>"<p><b>A</b>) Weight of reproductive organs in 12-week-old mice (n>6). Mann-Whitney: **, p<0.01; ***, p<0.001. <b>B</b>) Schematic of the spermatogenic lineage, testis support cells and the earliest stage of interference by p110β. <b>C</b>) H&E-stained sections of 12-week-old and 37-week-old testis and 12-week-old epididymis. sg, spermatogonia; sz, spermatozoa; SC, Sertoli cell; L, Leydig cell; #, presence of germ cells in p110β<sup><b>D931A/D931A</b></sup> seminiferous tubules; *, abnormally detached undifferentiated spermatids. Lumen size is indicated by double ended arrows. Scale: 20 μm. <b>D</b>) mRNA expression levels of the indicated genes at 12-week-old as determined by RT-qPCR normalized with 18S expression and corrected for total testis weight (n = 4). Student's t-test: non-significant. <b>E</b>) Immunofluorescence staining for JAM-A (Sertoli cell-specific protein localized in tight junctions) and JAM-C (spermatid-specific protein) counterstained with DAPI on cryosections of testes of 12-week-old mice (n = 3) [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005304#pgen.1005304.ref064\" target=\"_blank\">64</a>]. * indicate cell membranes of Sertoli cells; white arrow are JAM-C positive spermatids. Scale: 20 μm. <b>F</b>) H&E-stained sections of testes during post-natal development (P10: n = 4; P15: n = 2; P35: n = 3). Scale: 20 μm. <b>G</b>) mRNA expression levels of the indicated genes at P15 (top panel) and 12 weeks (bottom panel) as determined by RT-qPCR normalized with 18S expression and corrected for total testis weight (n = 4). Student's t-test: *, p<0.05; **, p<0.01; ***, p<0.001.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471100, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g003", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_organismal_inactivation_of_p110_946_reveals_a_role_for_p110_946_in_SCs_/1471100", "title"=>"Systemic organismal inactivation of p110β reveals a role for p110β in SCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159093"], "description"=>"<p><b>A</b>) p110 protein expression in primary rat SC culture. <b>B</b>) Following genotyping, AMH-Cre<sup><b>+</b></sup> testes were checked for <i>Pik3cb</i> recombination levels by a RT-nested PCR. No recombination was detected in Cre<sup><b>-</b></sup> testis (not shown) or in other organs. PCR 1 for <i>Pik3cb</i> exons 16–24: WT 1067 bp; β-DEL 797 bp; PCR 2 for <i>Pik3cb</i> exons 19–23: WT 474 bp; β-DEL 204 bp. β-DEL amplicons in both PCRs are indicated with a yellow star, and were only detected after the second PCR, consistent with the fact that SCs are less abundant in testis than the spermatogenic lineage. <b>C</b>) Weight of the indicated organs in recombined AMH-Cre<sup><b>+</b></sup>p110β<sup><b>flox/flox</b></sup> mice, referred to as SCβ-DEL (n = 5). Mann-Whitney: *D) Histology of 12-week-old SCβ-DEL testes (n = 3). Lumen size is indicated by horizontal lines. Scale 50 μm. <b>E</b>) mRNA expression levels of the indicated genes in testes of 12-week-old mice (n = 4) mice as determined by RT-qPCR normalized with 18S expression and corrected for total testis weight (n = 4). Student's t-test: *, p<0.05. <b>F</b>) Breeding efficiency of WT and SCβ-DEL males crossed with WT C57BL/6 females (n = 5). Despite some variability in the histological phenotype, all mice with a recombined <i>Pik3cb</i> were found to be sterile. Unpaired t-test: **, p<0.01.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471101, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tissue_specific_inactivation_of_p110_946_in_SCs_causes_male_sterility_/1471101", "title"=>"Tissue-specific inactivation of p110β in SCs causes male sterility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/2159094"], "description"=>"<p><b>A</b>) mRNA expression of selected markers in adult testes of mice with the indicated genotypes as determined by RT-qPCR and normalized with 18S expression and corrected for total testis weight (n>4). Student's t-test: **, p<0.01; ***, p<0.001. <b>B</b>) Functional classification of genes with >2-fold altered expression in testes of p110β<sup><b>D931A/WT</b></sup> males, compared to WT mice (for details see <b><a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005304#pgen.1005304.s016\" target=\"_blank\">S3 Table</a></b>). <b>C</b>) Gene expression pattern in p110β<sup><b>D931A/WT</b></sup> testis compared to SCARKO testis [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005304#pgen.1005304.ref038\" target=\"_blank\">38</a>] (for details see <b><a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005304#pgen.1005304.s017\" target=\"_blank\">S4 Table</a></b>). <b>D</b>) Schematic representation of plasmids transiently transfected in MSC-1 cells. <b>E</b>) Transient co-transfection of Rhox5-AREs luciferase reporter and Flag-AR of MSC-1 cells. 5α-DHT (5 and 50 nM) was used to activate AR transactivation activity. TGX-221 was used at 100 nM. Results are presented as induction factors (averages ± SEM of ≥3 independent experiments performed in triplicate). Student's t-test: **, p<0.01. <b>F</b>) mRNA expression of Rhox5 in testes of mice of the indicated genotypes (n>4) as determined by RT-qPCR and normalized with 18S expression and corrected for total testis weight. Student's t-test: *, p<0.05.</p>", "links"=>[], "tags"=>["p 110β inactivation", "Androgen Receptor Activity", "PI 3Kisoform p 110β", "p 110β", "sc", "p 110β results", "ar"], "article_id"=>1471102, "categories"=>["Uncategorised"], "users"=>["Julie Guillermet-Guibert", "Lee B. Smith", "Guillaume Halet", "Maria A. Whitehead", "Wayne Pearce", "Diane Rebourcet", "Kelly León", "Pascale Crépieux", "Gemma Nock", "Maria Strömstedt", "Malin Enerback", "Claude Chelala", "Mariona Graupera", "John Carroll", "Sabina Cosulich", "Philippa T. K. Saunders", "Ilpo Huhtaniemi", "Bart Vanhaesebroeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005304.g005", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_p110_946_activity_regulates_AR_mRNA_targets_specifically_in_SCs_/1471102", "title"=>"p110β activity regulates AR mRNA targets specifically in SCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-01 04:14:14"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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