CORTICOTROPHIN INCREASES CEREBRAL POLYAMINE CONTENT

Abstract— To determine whether changes in cerebral polyamines might mediate previously reported ACTH-induced changes in brain biochemistry and behavior, the cerebral content of polyamines was examined following ACTH treatment. Male CD-1 mice were injected daily for 3 days with long-acting (zinc phosphate) preparations of ACTH_1–24 (1 μg/g) or ACTH_4–10 (0.33 μg/g) and killed 24 h after the last injection. Putrescine, spermidine and spermine contents were determined by high pressure liquid chromatography. Putrescine content was significantly elevated in all brain regions by ACTH_1–24 (approx 50%), and in the telencephalon by ACTH_4–10 At the dose tested ACTH_4–10 was less effective than ACTH_1–24. Telencephalic spermidine was also elevated (10%)by ACTH_1–24, but spermine content was not altered in any brain region. One injection of the long-acting ACTH_1–24 preparation elevated telencephalic putrescine (49%) 24 h post-injection. ACTH_1–24 (1 μg/g) in saline produced a peak elevation of all three telencephalic polyamines 6 h post-injection, while in the liver only putrescine was significantly elevated and reached a peak at 10h. Neither plasma polyamine nor ornithine concentrations were significantly altered by any of the treatments. Corticosterone, in both single and multiple injection regimens, failed to alter telencephalic polyamine content. Adrenalectomy, however, prevented the ACTH_1–24-induced increase in telencephalic polyamines. It is concluded that ACTH acts directly in the brain to increase cerebral polyamine concentrations. The possibility that adrenal hormones exert permissive effects on this action is discussed.