RESUMO
Stress stimulates the sympathoadrenal system, causing activation of the catecholamine biosynthetic enzymes. Here we examine the changes of gene expression of tyrosine hydroxylase (TH; EC 1.14.16.2), the initial enzyme of catecholamine biosynthesis, with stress. A single immobilization of rats led to a large transient elevation in TH mRNA and a small elevation in TH immunoreactive protein and activity. Repeated daily immobilizations triggered more sustained changes in TH mRNA levels. After two immobilizations, the levels remained elevated even 3 days later. The rise in TH mRNA was followed by increased immunoreactive protein but only a small elevation in activity. With seven repeated immobilizations, the animals did not appear to adapt and still manifested a further rise in TH mRNA. TH activity was markedly elevated and returned to control levels 7 days after the immobilization. The rise in TH mRNA with a single immobilization occurred even in adrenals of hypophysectomized rats that underwent splanchnic nerve section. Immobilization for 30 min was sufficient to increase TH mRNA. The effect was abolished by the transcriptional inhibitor actinomycin D. Mobility gel-shift assays revealed increased binding of c-Fos and c-Jun to the AP-1 transcription factor site after a single immobilization, and the binding was not further elevated with repeated stress. This study shows that a single immobilization can activate TH gene expression by a nonneuronal nonpituitary-mediated pathway associated with increased binding of AP-1 transcription factors.
Assuntos
Glândulas Suprarrenais/enzimologia , Expressão Gênica , Hipofisectomia , Estresse Psicológico , Tirosina 3-Mono-Oxigenase/biossíntese , Animais , Sequência de Bases , Sítios de Ligação , Núcleo Celular/metabolismo , Cinética , Masculino , Dados de Sequência Molecular , Neurônios/fisiologia , Oligodesoxirribonucleotídeos , Hipófise/fisiologia , Hipófise/fisiopatologia , Proteínas Proto-Oncogênicas c-jun/isolamento & purificação , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Restrição Física , Circulação Esplâncnica , Transcrição GênicaRESUMO
Adult rats of both sexes were injected an aqueous suspension of progesterone in a dose of 12.5 mg i.p. + 12.5 mg i.m. and 50% of the animals were subjected to immobilization stress for 150 minutes either immediately after the hormone administration or at various time intervals after that. Non injected rats served as controls. After decapitation the plasma corticosterone level and the activity of tyrosine aminotransferase and tryptophan pyrrolase in the liver was determined. It was found that in non immobilized animals all three parameters investigated were increased to a minor degree 3 hours after progesterone injection. In stressed rats the stimulatory effect of stress induced hypercorticosteronaemia on the activity of both enzymes was decreased at 14 and/or 20 hours after progesterone administration, no sex differences being observed. The potential usefulness of progesterone as inhibitor of exaggerated stress is underlined.
Assuntos
Fígado/enzimologia , Progesterona/farmacologia , Estresse Fisiológico/fisiopatologia , Animais , Corticosterona/sangue , Feminino , Masculino , Ratos , Ratos Endogâmicos , Restrição Física , Fatores Sexuais , Triptofano Oxigenase/metabolismo , Tirosina Transaminase/metabolismoRESUMO
An as yet undescribed biphasic response of liver tyrosine aminotransferase (TAT) activity to a single administration of a microcrystallic watery suspension of 25 mg of progesterone (Agolutin Depot, SPOFA Praha) is described in adult female rats subjected to immobilization stress for 150 min. Exaggeration of the stress induced increase of TAT activity 3 and 8 h after hormone administration and its suppression 20 h after it was observed. The stress induced serum corticosterone increase is not correlated with the described changes, however, in non-stressed animals an increased TAT activity at 3 and 8 h after progesterone injection tightly follows the increased plasma corticosterone values. No statistically significant changes were found with respect to liver tryptophan pyrrolase activity.
Assuntos
Fígado/enzimologia , Progesterona/farmacologia , Estresse Fisiológico/metabolismo , Tirosina Transaminase/metabolismo , Animais , Corticosterona/sangue , Feminino , Ratos , Ratos Endogâmicos , Restrição Física , Triptofano Hidroxilase/metabolismo , Tirosina Transaminase/antagonistas & inibidoresRESUMO
In adult male rats anaesthetized with pentobarbital the intravenous infusion of 0.5 micrograms.kg-1.min-1 of epinephrine increased liver phosphorylase a activity within 5 min, whereas later a weakening of the hormone effect was observed. After increasing the infusion rate to 1.0 micrograms.kg-1.min-1 and extending the study to more parameters, the diminishing effect on phosphorylase was confirmed and a similar response was established for liver cAMP. Concomitantly, a decrease and recovery of liver glycogen synthase a activity was observed. In rats with permanent catheters in one of their tail arteries for obtaining blood samples, the plasma epinephrine levels were shown to be permanently increased (from cca 1 pmol.ml-1 before infusion of 1.0 micrograms.kg-1.min-1 to more than 30 pmol.ml-1 during infusion) and remained at steady levels throughout the infusion. Therefore, the weakening of the epinephrine effect should be ascribed to changes at (or beyond) the catecholamine receptor level. A hitherto undescribed decrease of total glycogen synthase activity was observed during the infusions.
Assuntos
Epinefrina/farmacologia , Glicogênio Sintase/metabolismo , Glicogênio Hepático/metabolismo , Fígado/enzimologia , Fosforilase a/metabolismo , Fosforilases/metabolismo , Animais , AMP Cíclico/metabolismo , Epinefrina/administração & dosagem , Epinefrina/sangue , Infusões Intravenosas , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos EndogâmicosRESUMO
The inhibitory effect of daily s.c. administration of cca 50 micrograms kg-1 17-beta-estradiol on liver alanine aminotransferase activity of adult female rats, the absence of this effect after bilateral adrenalectomy and its reappearance after gluccorticoid substitution is described.
Assuntos
Alanina Transaminase/metabolismo , Estradiol/farmacologia , Fígado/enzimologia , Adrenalectomia , Animais , Dexametasona/farmacologia , Feminino , Fígado/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
Bilateral adrenalectomy inhibited the increase in liver tyrosine aminotransferase and tryptophan pyrrolase activity after s.c. administration of cca 50 micrograms 17-beta-estradiol (Agofollin SPOFA, Praha) per 1 kg body weight daily for 14 days. Moreover, the authors describe the restitution of the estrogen effect by peroral dexamethasone intake via the drinking saline offered to the animals during the period of Agofollin treatment. In rats substituted in this way the resulting enzyme activities even exceeded those caused by dexamethasone alone.