The uptake of [3H]-aldosterone by the brain and anterior pituitary (AP) was studied after i.v. injection of the isotope into adrenalectomized rats. The AP showed the higher uptake ratio (i.e., radioactivity in tissue/radioactivity in blood), while the brain regions examined (hippocampus, hypothalamus, amygdala, cerebellum and cortex) contained lower levels of radioactivity, although they concentrated the hormone from blood. Neither [3H]-corticosterone nor [3H]-18-hydroxydeoxycorticosterone accumulated in the AP as much as [3H]-aldosterone, while [3H]-corticosterone's uptake was greatest in the hippocampus. Competition experiments demonstrated that [3H]-aldosterone uptake in the AP was inhibited by pretreatment of animals with excess aldosterone, corticosterone and dexamethasone, whereas aldosterone and corticosterone but not dexamethasone competed in the brain regions. Binding sites were demonstrated in vitro in cytosol fractions from AP and several brain regions. Scatchard plot analysis demonstrated high affinity, low capacity binding sites in cytosol from AP and hippocampus. These results suggest the AP and brain areas may be considered as targets for aldosterone, although the functions of the mineralocorticoid in these tissues are a matter of speculation.
In diabetic rats, 3H-estradiol binding by the cytosol and nuclei of the anterior pituitary was lower than normal. Changes in affinity and receptor numbers were demonstrated by Scatchard analysis. Protein synthesis in diabetic pituitaries, however, was in the normal range.
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.
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