H-2 gene complex and corticosteroid responsiveness: evidence that the corticosteroid hormone signal transduction pathway in the adult mouse lung is not associated with haplotype-specific responses to corticosteroids.
Differential responsiveness to corticosteroids (CORT) has been shown to be related to HLA haplotype. A strong association between the mouse homolog to the human HLA complex, the H-2 complex, and intrauterine responses to CORT have also been demonstrated; haplotype differences alter CORT-induced susceptibility to cleft palate and temporal differences in lung maturation. Since variation in the glucocorticoid receptor (GR) is associated with tissue specific responses to CORT, we hypothesize that haplotype-specific CORT responsiveness may be regulated by H-2 associated modification of GR expression and/or function. Given that H-2 congenic mice are genetically identical except at the H-2 complex on mouse chromosome 17 and the GR structural gene is encoded on chromosome 18, the GR gene is identical in these mice. However, any step in the GR signal transduction pathway may be regulated by gene(s) at or near the H-2 complex and result in haplotype-specific differences in CORT responsiveness. We have investigated differences in qualitative and quantitative characteristics of the adult B10 (H-2b) and B10.A (H-2a) pulmonary GR by Scatchard analysis, immunochemical and biochemical assays. No differences in the GR binding parameters (BMAX and Kd), receptor form and level, or ligand-GR complex binding to glucocorticoid response element (GR-GRE) were detected, leading us to conclude that H-2 associated factors do not regulate the relative intrauterine responses to CORT by modulating the adult GR.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaskoll
T
T
University of Southern California, Los Angeles 90089-0641.
Luttge
W G
WG
Sakai
D D
DD
Nichols
N R
NR
Melnick
M
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D000305:Adrenal Cortex Hormones; D006183:H-2 Antigens; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D004247:DNA