The polyamine stress response: tissue-, endocrine-, and developmental-dependent regulation.
Transient alterations in polyamine (PA) metabolism, termed the polyamine stress response (PSR), constitute a common cellular response to stressful stimuli. In contrast to the adult brain and liver, the PSR in the adrenal gland and thymus is characterized by a reduction in PA metabolism. The brain PSR undergoes an early postnatal period of non-responsiveness. The aim of the present study was twofold: i) to determine whether the PSR in the liver, thymus, and adrenal gland is developmentally regulated as that in the brain and ii) to establish whether neuronal and hormonal signals can activate the PSR independently. Ornithine decarboxylase (ODC) activity and tissue PA concentrations served as markers of the PSR. Changes were measured in male Wistar rats during postnatal development and at 2 weeks after adrenalectomy in adults. Unlike the brain, the direction of the PSR in peripheral organs did not undergo developmental changes. After adrenalectomy, the PSR was not activated in the thymus and liver by acute (2-hr) restraint stress, but a characteristic PSR was induced in the hippocampus. However, dexamethasone injection (3 mg/kg) did induce a characteristic PSR in all organs of adrenalectomized rats. The results justify the following conclusions: i) Unlike peripheral organs, the PSR in the brain is developmentally regulated; ii) The developmental switch to a mature PSR in the brain corresponds in time to the cessation of the "stress hypo-responsive period" in the hypothalamic-pituitary-adrenocortical (HPA) axis; iii) In the periphery, the PSR appears to be dependent principally on stress-induced activation of the HPA axis and on increased circulating glucocorticoid concentrations rather than on neuronal activation; iv) In the brain, however, the PSR can be induced independently by glucocorticoids or by direct activation of the neuronal circuitry; and v) up-regulation of the PSR, as in the brain and liver, is constructive and may be implicated in cell survival, while its down-regulation, as in the adrenal and thymus, may be implicated in cell death.
Gilad
V H
VH
Laboratory of Neuroscience, Research and Development, Assaf Harofeh Medical Center, 70300, Zrifin, Israel. gmgilad@asaf.health.gov.il
Rabey
J M
JM
Kimiagar
Y
Y
Gilad
G M
GM
D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006728:Hormones / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000502:physiology; D011073:Polyamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development
D005938:Glucocorticoids; D006728:Hormones; D011073:Polyamines; D003907:Dexamethasone