Subcellular distribution of cyclic adenosine 3',5'-monophosphate-binding protein and estrogen receptors in control pituitaries and estrogen-induced pituitary tumors.
Binding of cyclic adenosine 3',5'-monophosphate (cAMP) and steroid receptors was studied in cytoplasmic and nuclear fractions of pituitaries from castrated rats, in rats subjected to acute (60 min) or short-term (4 days) estradiol (E2) treatment, and in diethylstilbestrol-induced pituitary tumors (DES-T). E2 receptors were primarily in nuclear extracts in all animals that were given estrogens, whereas cytosolic receptors were low to absent. Contrarily, castrated rats showed high quantities of cytoplasmic receptor but little in nuclear sites. The progestin receptor was induced only in 4-day E2-treated rats and in DES-T. cAMP binding was stimulated in cytosol from 4-day E2-treated rats and in DES-T, but a significant reduction in binding was also noted in nuclear extracts from DES-T. Scatchard analysis for the cytosolic cAMP-binding activity demonstrated a two-component system, and the increased cAMP binding obtained in DES-T seemed to be caused by an increase in the low-affinity, high-capacity binder [regulatory type II (RII) subunit of protein kinase]. Suggestion of the preferential estrogenic induction of RII was also obtained by DEAE-cellulose chromatography, which provided separation of RI and RII subunits. The results suggest that sustained estrogenization leads to induction of cytosolic cAMP-binding protein and increased levels of nuclear E2 receptor. In DES-T, this effect resulted in an inverse subcellular distribution of both binding proteins, which may be related to abnormal growth of the pituitary, as has been postulated for hormone-dependent mammary tumors.
Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
G
G
Piroli
L S
LS
Weisenberg
C
C
Grillo
A F
AF
De Nicola
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002848:Chromatography, DEAE-Cellulose; D002373:Cyclic AMP Receptor Protein; D003600:Cytosol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011953:Receptors, Cyclic AMP / Q000187:drug effects* / Q000378:metabolism; D011959:Receptors, Estradiol / Q000187:drug effects* / Q000378:metabolism
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D004967:Estrogens; D011953:Receptors, Cyclic AMP; D011959:Receptors, Estradiol; D015056:1-Methyl-3-isobutylxanthine