Adrenocortical nuclear progesterone-binding protein: identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin.
Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinct from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.
Demura
T
T
Section on Adrenal Cell Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Driscoll
W J
WJ
Lee
Y C
YC
Strott
C A
CA
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002846:Chromatography, Affinity; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006168:Guinea Pigs; D008970:Molecular Weight; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011376:Progesterone-Binding Globulin / Q000302:isolation & purification / Q000378:metabolism* / Q000528:radiation effects; D014316:Tritium; D014466:Ultraviolet Rays
D011376:Progesterone-Binding Globulin; D013196:Dihydrotestosterone; D014316:Tritium; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D004247:DNA