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David R Joseph - One of the best experts on this subject based on the ideXlab platform.
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sequence and functional relationships between androgen binding Protein sex hormone binding globulin and its homologs Protein s gas6 laminin and agrin
Steroids, 1997Co-Authors: David R JosephAbstract:Abstract Androgen-Binding Protein/sex hormone-binding globulin ( ABP SHBG ) is an extracellular binding Protein that regulates the bioavailability of sex steroids. ABP SHBG is closely related to the globular (G) domain of vitamin K-dependent Protein S family of Proteins and more distantly related to the G domains of several extracellular matrix Proteins. ABP SHBG appears to have evolved from the fusion of two ancestral G domains. Expanding evidence suggests that ABP SHBG has other functions that are mediated through membrane binding, including signal transduction; however, the types of binding Proteins (receptors) have not been identified. Sequence comparisons of ABP SHBG with G domains of its homologs Protein S, Gas6, laminin, and agrin have identified regions of ABP SHBG that may bind receptors related to homolog receptors. These membrane receptors include β-integrins, α-dystroglycan, and receptor tyrosine kinases. The G domains of laminin and related Proteins have clearly evolved from a common ancestor to interact with specific receptors and binding Proteins. It remains to be determined if ABP SHBG followed this evolutionary pathway.
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structure function and regulation of androgen binding Protein sex hormone binding globulin
Vitamins and Hormones Series, 1994Co-Authors: David R JosephAbstract:Despite over 20 years of research, the functions of ABP and SHBG remain elusive. The major reason for this lack of knowledge has been the unavailability of natural mutants with clinical defects for study. There is strong evidence that these binding Proteins do act to modulate the gene regulatory actions of nuclear sex steroid receptors by controlling the availability of androgens and estrogens. In plasma, SHBG controls the metabolic clearance rate of sex steroids. In addition there is strong evidence that they have a much broader function. The identification of plasma membrane receptors in target tissues and the finding of homologous domains in several developmental Proteins support other functions. Moreover, other experiments suggest the Proteins may actually be hormones or growth factors. These findings are not compatible with a model that has the Proteins only regulating free steroid hormone levels. Obviously, much more experimentation will be necessary to reveal the functions of ABP and SHBG. The recent discoveries have offered several clues to their functions and open new routes for study. These experiments, coupled with newly developed techniques, such as gene knockout by homologous recombination, make one optimistic that the functions of these unique Proteins will be deciphered in the near future.
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identification of an alternate promoter in the rat androgen binding Protein sex hormone binding globulin gene that regulates synthesis of a messenger rna encoding a Protein with altered function
Molecular Endocrinology, 1993Co-Authors: Patrick Sullivan, Yanmin Wang, David R JosephAbstract:Extracellular Androgen-Binding Proteins (ABP) are thought to modulate the regulatory functions of androgens. These Proteins, which are secreted by the testis (ABP) and liver [sex hormone-binding globulin (SHBG)], are encoded by the same gene. In a previous study, the rat ABP/SHBG gene was sequenced, and a promoter (P1) was identified by primer extension. This promoter regulates synthesis of the mRNA that encodes secreted testicular ABP and fetal liver SHBG. In this study, the P1 transcriptional start site in testis and fetal liver was confirmed by RNase protection assays. We also identified an alternate promoter (PA) in the ABP/SHBG gene located 15 kilobases up-stream from the previously characterized testicular promoter (P1). The PA region has the characteristics of a GC-rich housekeeping-type promoter. RNAase protection and primer walking experiments with RNA polymerase chain reaction identified a region where the major sites of transcription initiation occur. Promoter PA directs the synthesis of altern...
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identification of an alternate promoter in the rat androgen binding Protein sex hormone binding globulin gene that regulates synthesis of a messenger rna encoding a Protein with altered function
Molecular Endocrinology, 1993Co-Authors: Patrick Sullivan, Yanmin Wang, David R JosephAbstract:Extracellular Androgen-Binding Proteins (ABP) are thought to modulate the regulatory functions of androgens. These Proteins, which are secreted by the testis (ABP) and liver [sex hormone-binding globulin (SHBG)], are encoded by the same gene. In a previous study, the rat ABP/SHBG gene was sequenced, and a promoter (P1) was identified by primer extension. This promoter regulates synthesis of the mRNA that encodes secreted testicular ABP and fetal liver SHBG. In this study, the P1 transcriptional start site in testis and fetal liver was confirmed by RNase protection assays. We also identified an alternate promoter (PA) in the ABP/SHBG gene located 15 kilobases up-stream from the previously characterized testicular promoter (P1). The PA region has the characteristics of a GC-rich housekeeping-type promoter. RNAase protection and primer walking experiments with RNA polymerase chain reaction identified a region where the major sites of transcription initiation occur. Promoter PA directs the synthesis of alternate ABP RNAs, which contain an alternate exon 1 (exon A) sequence. One alternate ABP RNA, which contains exons A and 2-8 sequences, is expressed in testis, fetal liver, and brain. This alternate ABP RNA encodes an ABP-like Protein (46,000 daltons) with an altered N-terminal sequence without a secretory signal peptide. Expression of the ABP-like Protein in COS cells revealed that it is not secreted and does not appear to bind dihydrotestosterone. Another similar alternate ABP RNA is missing exon 6 sequence and encodes a nonsecretory truncated Protein (28,000 daltons) that does not bind androgen. The functions of the ABP-like Proteins are not obvious, but their functions are clearly different from secreted ABP and SHBG.
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sex hormone binding globulin androgen binding Protein and vitamin k dependent Protein s are homologous to laminin a merosin and drosophila crumbs Protein
The FASEB Journal, 1992Co-Authors: David R Joseph, Michael E BakerAbstract:Androgen-Binding Protein (ABP) and sex hormone-binding globulin (SHBG) are extracellular steroid-binding Proteins that are homologous to the COOH-terminal domain of vitamin K-dependent Protein S, a Protein important in blood clotting. We find that the sequences of ABP, SHBG, and Protein S are also similar to two basement membrane Proteins, laminin and merosin, and to an integral membrane Protein, Drosophila crumbs Protein. These latter three Proteins have important roles in regulating differentiation and development. The sequence similarity corresponds to the G domain of laminin A chain, which binds heparin and type IV collagen. Analysis of a multiple alignment of these Proteins reveals one well-conserved segment corresponding to the part of SHBG that binds to its membrane receptor and another corresponding to the part of Protein S that binds to C4b-binding Protein. The similarities suggest that ABP, SHBG, and Protein S may also have functions related to that of laminin and merosin.
J. Arunakaran - One of the best experts on this subject based on the ideXlab platform.
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protective role of lycopene on polychlorinated biphenyls aroclor 1254 induced adult rat sertoli cell dysfunction by increased oxidative stress and endocrine disruption
Biomedicine & Preventive Nutrition, 2011Co-Authors: Gunasekaran Krishnamoorthy, P Venkataraman, Kandaswamy Selvakumar, Perumal Elumalai, J. ArunakaranAbstract:Abstract The protective role of lycopene against various toxicants on various organs and its association with decreased oxidative stress seems to be well established. Sertoli cell function in the adult testis determines daily sperm production. Increasing evidence suggests that environmental pollutants including polychlorinated biphenyls (PCBs) are male infertility, which is associated with oxidative stress. Hence, the present study was designed to find out whether PCBs disrupt Sertoli cell function by inducing oxidative stress or endocrine disruption? Whether lycopene attenuates PCBs-induced disruption in Sertoli cells or not? Adult male rats were divided into four (vehicle control, lycopene, PCBs and PCBs + lycopene treated) groups. After the experimental period (30 days), the animals were decapitated for the blood collection and testes were removed for the isolation of Sertoli cells. In PCBs exposure, serum hormones (FSH, testosterone and estradiol), Sertoli cellular receptors (FSHR and AR) were significantly decreased whereas oxidative stress markers (H 2 O 2 and LPO) and ER-s expression in Sertoli cells were significantly increased. Sertoli cell functional Proteins such as connexin 43, transferrin and Androgen-Binding Protein expressions and the level of lactate were significantly decreased. However, simultaneous supplementation of lycopene to PCBs-exposed rats significantly decreased the endocrine disruption and oxidative stress in Sertoli cells. The findings point out that lycopene protects the Sertoli cell function by preventing PCBs-induced oxidative stress and endocrine disruption.
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effects of vitamins c and e on steroidogenic enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell steroidogenic acute regulatory (StAR) Protein and steroidogenic enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding Protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR Protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding Protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while steroidogenic enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
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effect of aroclor 1254 on sertoli cellular antioxidant system androgen binding Protein and lactate in adult rat in vitro
Toxicology, 2005Co-Authors: Gunasekaran Krishnamoorthy, Palaniappan Murugesan, M M Aruldhas, R Muthuvel, D N Gunadharini, M R Vijayababu, A Arunkumar, P Venkataraman, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10 −10 to 10 −7 M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (γ-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding Protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10 −10 to 10 −7 M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.
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effects of vitamin c and e on pcb aroclor 1254 induced oxidative stress androgen binding Protein and lactate in rat sertoli cells
Reproductive Toxicology, 2004Co-Authors: Senthil J Kumar, Palaniappan Murugesan, K Balasubramanian, M M Aruldhas, Sivanantham Banudevi, M Sharmila, N Srinivasan, J. ArunakaranAbstract:The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding Protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.
Christina M Laukaitis - One of the best experts on this subject based on the ideXlab platform.
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did androgen binding Protein paralogs undergo neo and or subfunctionalization as the abp gene region expanded in the mouse genome
PLOS ONE, 2014Co-Authors: Robert C Karn, Amanda G Chung, Christina M LaukaitisAbstract:The Androgen-Binding Protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as Proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified Proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding Proteins are expressed at very low levels compared to those transcripts with Proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding Protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution.
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congenic strain analysis reveals genes that are rapidly evolving components of a prezygotic isolation mechanism mediating incipient reinforcement
PLOS ONE, 2012Co-Authors: Christina M Laukaitis, Corina Mauss, Robert C KarnAbstract:Two decades ago, we developed a congenic strain of Mus musculus, called b-congenic, by replacing the Androgen-Binding Protein Abpa27 a allele in the C3H/HeJ genome with the Abpa27 b allele from DBA/2J. We and other researchers used this bcongenic strain and its C3H counterpart, the a-congenic strain, to test the hypothesis that, given the choice between signals from two strains with different a27 alleles on the same genetic background, test subjects would prefer the homosubspecific one. It was our purpose in undertaking this study to characterize the segment transferred from DBA to the C3H background in producing the b-congenic strain on which a role for ABPA27 in behavior has been predicated. We determined the size of the chromosome 7 segment transferred from DBA and the genes it contains that might influence preference. We found that the ‘‘functional’’ DBA segment is about 1% the size of the mouse haploid genome and contains at least 29 genes expressed in salivary glands, however, only three of these encode Proteins identified in the mouse salivary proteome. At least two of the three genes Abpa27, Abpbg26 and Abpbg27 encoding the subunits of Androgen-Binding Protein ABP dimers evolved under positive selection and the third one may have also. In the sense that they are subunits of the same two functional entities, the ABP dimers, we propose that their evolutionary histories might not be independent of each other.
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a candidate subspecies discrimination system involving a vomeronasal receptor gene with different alleles fixed in m m domesticus and m m musculus
PLOS ONE, 2010Co-Authors: Robert C Karn, Janet M. Young, Christina M LaukaitisAbstract:Assortative mating, a potentially efficient prezygotic reproductive barrier, may prevent loss of genetic potential by avoiding the production of unfit hybrids (i.e., because of hybrid infertility or hybrid breakdown) that occur at regions of secondary contact between incipient species. In the case of the mouse hybrid zone, where two subspecies of Mus musculus (M. m. domesticus and M. m. musculus) meet and exchange genes to a limited extent, assortative mating requires a means of subspecies recognition. We based the work reported here on the hypothesis that, if there is a pheromone sufficiently diverged between M. m. domesticus and M. m. musculus to mediate subspecies recognition, then that process must also require a specific receptor(s), also sufficiently diverged between the subspecies, to receive the signal and elicit an assortative mating response. We studied the mouse V1R genes, which encode a large family of receptors in the vomeronasal organ (VNO), by screening Perlegen SNP data and identified one, Vmn1r67, with 24 fixed SNP differences most of which (15/24) are nonsynonymous nucleotide substitutions between M. m. domesticus and M. m. musculus. We observed substantial linkage disequilibrium (LD) between Vmn1r67 and Abpa27, a mouse salivary Androgen-Binding Protein gene that encodes a Proteinaceous pheromone (ABP) capable of mediating assortative mating, perhaps in conjunction with its bound small lipophilic ligand. The LD we observed is likely a case of association rather than residual physical linkage from a very recent selective sweep, because an intervening gene, Vmn1r71, shows significant intra(sub)specific polymorphism but no inter(sub)specific divergence in its nucleotide sequence. We discuss alternative explanations of these observations, for example that Abpa27 and Vmn1r67 are coevolving as signal and receptor to reinforce subspecies hybridization barriers or that the unusually divergent Vmn1r67 allele was not a product of fast positive selection, but was derived from an introgressed allele, possibly from Mus spretus.
Robert C Karn - One of the best experts on this subject based on the ideXlab platform.
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did androgen binding Protein paralogs undergo neo and or subfunctionalization as the abp gene region expanded in the mouse genome
PLOS ONE, 2014Co-Authors: Robert C Karn, Amanda G Chung, Christina M LaukaitisAbstract:The Androgen-Binding Protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as Proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified Proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding Proteins are expressed at very low levels compared to those transcripts with Proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding Protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution.
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congenic strain analysis reveals genes that are rapidly evolving components of a prezygotic isolation mechanism mediating incipient reinforcement
PLOS ONE, 2012Co-Authors: Christina M Laukaitis, Corina Mauss, Robert C KarnAbstract:Two decades ago, we developed a congenic strain of Mus musculus, called b-congenic, by replacing the Androgen-Binding Protein Abpa27 a allele in the C3H/HeJ genome with the Abpa27 b allele from DBA/2J. We and other researchers used this bcongenic strain and its C3H counterpart, the a-congenic strain, to test the hypothesis that, given the choice between signals from two strains with different a27 alleles on the same genetic background, test subjects would prefer the homosubspecific one. It was our purpose in undertaking this study to characterize the segment transferred from DBA to the C3H background in producing the b-congenic strain on which a role for ABPA27 in behavior has been predicated. We determined the size of the chromosome 7 segment transferred from DBA and the genes it contains that might influence preference. We found that the ‘‘functional’’ DBA segment is about 1% the size of the mouse haploid genome and contains at least 29 genes expressed in salivary glands, however, only three of these encode Proteins identified in the mouse salivary proteome. At least two of the three genes Abpa27, Abpbg26 and Abpbg27 encoding the subunits of Androgen-Binding Protein ABP dimers evolved under positive selection and the third one may have also. In the sense that they are subunits of the same two functional entities, the ABP dimers, we propose that their evolutionary histories might not be independent of each other.
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a candidate subspecies discrimination system involving a vomeronasal receptor gene with different alleles fixed in m m domesticus and m m musculus
PLOS ONE, 2010Co-Authors: Robert C Karn, Janet M. Young, Christina M LaukaitisAbstract:Assortative mating, a potentially efficient prezygotic reproductive barrier, may prevent loss of genetic potential by avoiding the production of unfit hybrids (i.e., because of hybrid infertility or hybrid breakdown) that occur at regions of secondary contact between incipient species. In the case of the mouse hybrid zone, where two subspecies of Mus musculus (M. m. domesticus and M. m. musculus) meet and exchange genes to a limited extent, assortative mating requires a means of subspecies recognition. We based the work reported here on the hypothesis that, if there is a pheromone sufficiently diverged between M. m. domesticus and M. m. musculus to mediate subspecies recognition, then that process must also require a specific receptor(s), also sufficiently diverged between the subspecies, to receive the signal and elicit an assortative mating response. We studied the mouse V1R genes, which encode a large family of receptors in the vomeronasal organ (VNO), by screening Perlegen SNP data and identified one, Vmn1r67, with 24 fixed SNP differences most of which (15/24) are nonsynonymous nucleotide substitutions between M. m. domesticus and M. m. musculus. We observed substantial linkage disequilibrium (LD) between Vmn1r67 and Abpa27, a mouse salivary Androgen-Binding Protein gene that encodes a Proteinaceous pheromone (ABP) capable of mediating assortative mating, perhaps in conjunction with its bound small lipophilic ligand. The LD we observed is likely a case of association rather than residual physical linkage from a very recent selective sweep, because an intervening gene, Vmn1r71, shows significant intra(sub)specific polymorphism but no inter(sub)specific divergence in its nucleotide sequence. We discuss alternative explanations of these observations, for example that Abpa27 and Vmn1r67 are coevolving as signal and receptor to reinforce subspecies hybridization barriers or that the unusually divergent Vmn1r67 allele was not a product of fast positive selection, but was derived from an introgressed allele, possibly from Mus spretus.
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the role of salivary androgen binding Protein in reproductive isolation between two subspecies of house mouse mus musculus musculus and mus musculus domesticus
Biological Journal of The Linnean Society, 2005Co-Authors: Robert C Karn, Barbora Voslajerova Bimova, Jaroslav PialekAbstract:Previous behavioural studies using inbred lines have suggested that the gene (Abpa) for the alpha subunit of salivary Androgen-Binding Protein (ABP) plays a role in prezygotic isolation between house mouse Mus musculus subspecies. We tested this hypothesis in animals from wild allopatric (121 individuals from four samples) and parapatric (320 animals from 15 samples) populations sampled on the Czech-Bavarian transect across the hybrid zone between M. m. domesticus and M. m. musculus. The study did not reveal a consistent statistically significant trend of homosubspecific preferences in individual allopatric and parapatric populations. Nonetheless, the whole pattern of preference was skewed toward homosubspecific preference mostly on the M. m. musculus side of the hybrid zone. The pattern of homosubspecific preferences was stronger for the time spent sniffing than it was for the first choice of the signal (the ratio of homosubspecific vs. heterosubspecific preferences for both sexes was 6 : 2 in allopatric and 21 : 9 in parapatric populations, while the same rates were 4 : 4 and 16 : 14 for the first choice). To the extent that Y-maze tests reflect preference under wild conditions, we suggest that this slight preference may not in itself be sufficient to impede gene flow between the two subspecies and thus act as a reproductive barrier. ABP most probably participates in a complex system of subspecies-specific recognition in the hybrid zone, but the picture is far too complex at this time to allow a conclusive evaluation of the importance of this role.
Palaniappan Murugesan - One of the best experts on this subject based on the ideXlab platform.
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effects of vitamins c and e on steroidogenic enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell steroidogenic acute regulatory (StAR) Protein and steroidogenic enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding Protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR Protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding Protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while steroidogenic enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
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effect of aroclor 1254 on sertoli cellular antioxidant system androgen binding Protein and lactate in adult rat in vitro
Toxicology, 2005Co-Authors: Gunasekaran Krishnamoorthy, Palaniappan Murugesan, M M Aruldhas, R Muthuvel, D N Gunadharini, M R Vijayababu, A Arunkumar, P Venkataraman, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic effects including reproductive toxicity. The present study was designed to investigate the impact of Aroclor 1254 on Sertoli cellular function and antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult rat testes and treated with various concentrations (10 −10 to 10 −7 M) of Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was assessed and the Sertoli cellular antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (γ-GT) and glutathione reductase (GR) and lipid peroxidation (LPO) were assayed. In addition, androgen binding Protein (ABP) and lactate secretions were also quantified in Sertoli cell culture medium. Sertoli cellular viability and activity of antioxidant enzymes were significantly reduced in Aroclor 1254 (10 −10 to 10 −7 M) treatment for 6, 12 and 24 h whereas, the Sertoli cellular lipid peroxidation was significantly increased in a dose and duration dependent manner. In addition, ABP secretion diminished and lactate secretion was significantly elevated in the same manner. To conclude, the present study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions such as ABP, lactate secretions and activity of antioxidant enzymes.
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effects of vitamin c and e on pcb aroclor 1254 induced oxidative stress androgen binding Protein and lactate in rat sertoli cells
Reproductive Toxicology, 2004Co-Authors: Senthil J Kumar, Palaniappan Murugesan, K Balasubramanian, M M Aruldhas, Sivanantham Banudevi, M Sharmila, N Srinivasan, J. ArunakaranAbstract:The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding Protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.