Disease relevance of Shbg

• Shbg is thus closely linked to several neurological mutations, one of which, Tr, is also associated with male sterility [1].

High impact information on Shbg

• Both the dephospho form (which blocks binding of GRIP/ABP and PICK1) and the phospho form (which selectively blocks PICK1) attenuated LTD induction by glutamate/depolarization pairing, as did antibodies directed against the PDZ domain of PICK1 [2].
• Phosphorylation of Ser-880 in this region by PKC differentially regulates the binding of the PDZ domain-containing proteins GRIP/ABP and PICK1 [2].
• Human actin binding protein (ABP) links specific membrane glycoproteins to cytoskeletal actin microfilaments [3].
• Allelic variation within the mouse androgen-binding protein (ABP) alpha subunit gene (Abpa) has been suggested to promote assortative mating and thus prezygotic isolation [4].
• Previous mapping experiments between EL and nonepileptic ABP mice identified, and a congenic strain confirmed, a quantitative trait locus (QTL), El2, which lowered the threshold to seizures induced by gentle rhythmic tossing [5].

Biological context of Shbg

• Southern hybridization analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4 gene is likely to span less than a total of 15 kb, and was mapped to chromosome (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses [6].
• The secreted glycoprotein appears to be a spermine binding protein since the nucleotide and predicted amino acid sequence of MP25 shares extensive homology with a spermine binding protein (SBP) found in rat ventral prostate [7].
• An ABP cDNA was isolated from a mouse testis cDNA library and encoded a protein (403 residues) with 89% of the amino acid residues identical to rat ABP, including a signal peptide [8].
• The mouse salivary androgen-binding protein (ABP) gene cluster on Chromosomes 7: characterization and evolutionary relationships [9].
• The number and type of testicular germ cells undergoing apoptosis in different age groups of mice (from 7 to 360 days of age) was determined and compared in age-matched wild type (WT) control and in a transgenic (TG) mice homozygous to rat androgen binding protein (ABP) using flow cytometry [10].

Anatomical context of Shbg

• Southern blot analysis of DNAs from Chinese hamster x mouse and rat x mouse somatic cell hybrids showed that the mouse gene encoding androgen-binding protein/sex hormone-binding globulin (ABP-SHBG) is on Chromosome 11 [1].
• Repression of the human sex hormone-binding globulin gene in Sertoli cells by upstream stimulatory transcription factors [11].
• ABP subunits appear to dimerize randomly and a model is presented demonstrating the origin of six ABP dimers in the salivas of AbpaaAbpga/AbpabAbpgb heterozygous mice [12].
• A 1.7 kilobase mRNA, homologous with rat ABP cDNA, was identified in mouse testis and Sertoli cells by Northern blot hybridization, but at a much lower level than in the rat [8].
• Mouse salivary androgen-binding protein (ABP) is a major secretory product of the submaxillary glands [13].

Associations of Shbg with chemical compounds

• Genetic mapping of the gene for androgen-binding protein/sex hormone-binding globulin to mouse chromosome 11 [1].
• The results of cell-free translation studies in which the pre-ABP subunits are identified specifically by immunoprecipitation with anti-ABP antibody supports the idea that independent mRNAs code for the Alpha, Beta and Gamma subunits [12].
• Steroid-binding, radioimmunoassay and immunocytochemical studies demonstrated that ABP is present in mouse testis and epididymis, but at 1/50 to 1/25 the level of rat epididymis [8].
• Immunohistochemical detection of proteins on electroblots of polyacrylamide electrophoresis and isoelectric focusing gels, however shows that the prostate CRM is a protein with electrophoretic and isoelectric focusing behavior distinct from that of salivary ABP isoproteins [14].
• Human SHBG transcripts were found within their Sertoli cells, primary cultures of which secrete human SHBG, and this was increased by treatment with follicle-stimulating hormone, retinoic acid, and estradiol but not testosterone [11].

Regulatory relationships of Shbg

• Our results indicate that ABP is expressed in the mouse and past failures to detect androgen-binding activity were due to the low level of ABP protein [8].

Other interactions of Shbg

• Progeny from an intersubspecies backcross were analyzed to position this locus, termed Shbg, between Il-3 and Int-4 in the middle of this chromosome [1].
• The glands expressing Abp paralogues produce secretions (lacrimal and salivary) or detect odors (MOE and VNO) and thus it appears highly likely that ABP proteins play a role in olfactory communication [15].
• The extracellular domains of alpha-neurexins are composed of six LNS repeats, named after homologous sequences in the Laminin A G domain, Neurexins, and Sex hormone-binding globulin, with three interspersed epidermal growth factor-like domains [16].

Analytical, diagnostic and therapeutic context of Shbg

• In situ hybridization of an shbg11 transgenic mouse fetus at 17.5 days postcoitus located human shbg transcripts only in duodenal epithelial cells and hepatocytes [17].
• Alternative ELISA for sex hormone-binding globulin in plasma [18].
• Immunoradiometric assay of sex-hormone binding globulin with use of two different monoclonal antibodies [19].
• The antibody-binding protein (ABP) solubilized from platelets, cerebellum, and smooth muscle chromatographed identically on gel filtration, anion-exchange and heparin-TSK h.p.l.c. ABP was purified to apparent homogeneity from platelets and aortic smooth muscle as a 63 kDa protein by immunoaffinity chromatography on mAb 213-21-agarose [20].
• Increased levels of ERbeta mRNA and protein were demonstrated in the testis of rat ABP transgenic mice compared with nontransgenic littermates by reverse transcriptase-polymerase chain reaction (RT-PCR) experiments, Northern blotting, and Western Blotting [21].

References