Abstract
The hormone binding activity of glucocorticoid receptors is decreased by approximately equal to 75% in the livers of mice homozygous for c14CoS, one of several overlapping radiation-induced deletions on chromosome 7. These deletions have been shown previously to map at and around the albino (c) locus and to act as recessive lethals. They are associated with intractable hypoglycemia, ultrastructural abnormalities in certain liver cell membranes, and deficiencies of specific liver proteins and enzymes that are induced by insulin or glucocorticoids, or both. Scatchard analysis of [3H]dexamethasone binding to receptors in control and mutant liver extracts revealed that the glucocorticoid binding constants were similar; however, the control extracts bound approximately equal to 4 times as much steroid as did mutant extracts. Analysis by DNA-cellulose column chromatography demonstrated that the ability of activated glucocorticoid receptors to form complexes with DNA appears to be unaltered in the mutants; both mutant and control cytosols contain glucocorticoid receptors that elute from DNA-cellulose columns at two different salt concentrations. Sucrose density gradient centrifugation revealed the glucocorticoid receptors in mutant livers to have approximately the same sedimentation coefficient as receptors in control livers. The decrease in glucocorticoid binding activity in mutant liver cell extracts is comparable in degree to that previously reported for insulin binding activity. The gene sequences deleted in the homozygous deletion mutants appear to be instrumental in the regulation rather than the structural determination of both glucocorticoid and insulin receptors.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cousens L., Eskin B. Filter assay method for the estrogen receptor protein: detection of both filled and unfilled estrogen binding sites. Anal Biochem. 1982 Mar 15;121(1):39–48. doi: 10.1016/0003-2697(82)90554-1. [DOI] [PubMed] [Google Scholar]
- Erickson R. P., Gluecksohn-Waelsch S., Cori C. F. Glucose-6-phosphatase deficiency caused by radiation-induced alleles at the albino locus in the mouse. Proc Natl Acad Sci U S A. 1968 Feb;59(2):437–444. doi: 10.1073/pnas.59.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garland R. C., Satrustegui J., Gluecksohn-Waelsch S., Cori C. F. Deficiency in plasma protein synthesis caused by x-ray-incuded lethal albino alleles in mouse. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3376–3380. doi: 10.1073/pnas.73.10.3376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gluecksohn-Waelsch S. Genetic control of morphogenetic and biochemical differentiation: lethal albino deletions in the mouse. Cell. 1979 Feb;16(2):225–237. doi: 10.1016/0092-8674(79)90001-1. [DOI] [PubMed] [Google Scholar]
- Goldfeld A. E., Rubin C. S., Siegel T. W., Shaw P. A., Schiffer S. G., Gluecksohn-Waelsch S. Genetic control of insulin receptors. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6359–6361. doi: 10.1073/pnas.78.10.6359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Ringold G. M., Yamamoto K. R., Bishop J. M., Varmus H. E. Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2879–2883. doi: 10.1073/pnas.74.7.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thorsson A. V., Hintz R. L. Insulin receptors in the newborn. Increase in receptor affinity and number. N Engl J Med. 1977 Oct 27;297(17):908–912. doi: 10.1056/NEJM197710272971704. [DOI] [PubMed] [Google Scholar]
- Trigg M. J., Gluecksohn-Waelsch S. Ultrastructural basis of biochemical effects in a series of lethal alleles in the mouse. Neonatal and developmental studies. J Cell Biol. 1973 Sep;58(3):549–563. doi: 10.1083/jcb.58.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto K. R., Gehring U., Stampfer M. R., Sibley C. H. Genetic approaches to steroid hormone action. Recent Prog Horm Res. 1976;32:3–32. doi: 10.1016/b978-0-12-571132-6.50008-7. [DOI] [PubMed] [Google Scholar]