RESUMO
The specific uptake of tritiated 18-hydroxycorticosterone (18-OH-B) by purified cell nuclear fractions and cytosol of medulla oblongata, pons, amygdala, anterior pituitary, hypothalamus, hippocampus, preoptic-area and lung from adrenalectomized animals was investigated after incubation of tissue sections with radioactive ligand. We found that 18-OH-B was taken up mainly by nuclei obtained from pons and medulla oblongata; this profile differs from previous observations with the closely related steroids corticosterone and aldosterone, which are mostly concentrated by the limbic system. Based on this finding, as well as on former studies with 18-OH-B, we suggest that this steroid may exert its action on renal excretion of protons as well as on central nervous system structures involved in respiratory regulation, related to that excretion.
Assuntos
18-Hidroxicorticosterona/farmacocinética , Sistema Nervoso Central/metabolismo , Frações Subcelulares/metabolismo , Adrenalectomia , Animais , Sítios de Ligação , Sistema Nervoso Central/citologia , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The specific uptake of tritiated 18-hydroxycorticosterone (18-OH-B) by purified cell nuclear fractions and cytosol of medulla oblongata, pons, amygdala, anterior pituitary, hypothalamus, hippocampus, preoptic-area and lung from adrenalectomized animals was investigated after incubation of tissue sections with radioactive ligand. We found that 18-OH-B was taken up mainly by nuclei obtained from pons and medulla oblongata; this profile differs from previous observations with the closely related steroids corticosterone and aldosterone, which are mostly concentrated by the limbic system. Based on this finding, as well as on former studies with 18-OH-B, we suggest that this steroid may exert its action on renal excretion of protons as well as on central nervous system structures involved in respiratory regulation, related to that excretion.
RESUMO
The specific uptake of tritiated 18-hydroxycorticosterone (18-OH-B) by purified cell nuclear fractions and cytosol of medulla oblongata, pons, amygdala, anterior pituitary, hypothalamus, hippocampus, preoptic-area and lung from adrenalectomized animals was investigated after incubation of tissue sections with radioactive ligand. We found that 18-OH-B was taken up mainly by nuclei obtained from pons and medulla oblongata; this profile differs from previous observations with the closely related steroids corticosterone and aldosterone, which are mostly concentrated by the limbic system. Based on this finding, as well as on former studies with 18-OH-B, we suggest that this steroid may exert its action on renal excretion of protons as well as on central nervous system structures involved in respiratory regulation, related to that excretion.
RESUMO
We have studied type I and type II adrenal cortical steroid receptors in the anterior (AL), intermediate (IL) and posterior (PL) lobes of the pituitary and in the hippocampus of ovariectomized-adrenalectomized female rats and in castrated-adrenalectomized male animals, with or without oestrogen treatment. Using [3H]dexamethasone as ligand and conditions suitable for determination of its binding to type I and type II receptors, we found that 4 or 15 days of oestrogen reduced type I receptors in AL by 50-60% without changes in IL, PL or hippocampus, or in type II sites in any of the four neuroendocrine tissues studied. This down-regulatory effect was seen only in female rats and no change was found for males. The reduction in type I sites in AL in oestrogenized female rats was confirmed by labelling type I sites with the synthetic antimineralocorticoid [3H]ZK 91587. Saturation analysis with [3H]ZK 91587 demonstrated that the reduction was due to a reduction in Bmax without change in Kd. We conclude that: (a) type I receptors in the anterior pituitary are under oestrogenic control; (b) there is a sex difference in the response to oestrogen of AL type I sites; and (c) this demonstration may be useful in determining the role of type I receptors in neuroendocrine regulation of the anterior pituitary by hormones derived from the adrenal cortex, and the participation of sex hormones in this process.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Estradiol/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Receptores do Hormônio Hipofisário/efeitos dos fármacos , Adrenalectomia , Animais , Castração , Dexametasona/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Mineralocorticoides/antagonistas & inibidores , Adeno-Hipófise/metabolismo , Neuro-Hipófise/efeitos dos fármacos , Neuro-Hipófise/metabolismo , Ratos , Ratos Endogâmicos , Receptores da Corticotropina , Receptores do Hormônio Hipofisário/classificação , Receptores do Hormônio Hipofisário/metabolismo , Fatores Sexuais , Espironolactona/análogos & derivados , Espironolactona/metabolismoRESUMO
Stereoselective competition was used to determine (3H)-aldosterone binding to type I corticosteroid receptors, and (3H)-dexamethasone binding to type II receptors in punches obtained from 11 brain regions of short-term adrenalectomized (ADX) rats. It was observed that type I receptor binding was almost exclusive of the hippocampus (HIPPO), while type II receptor binding was more generally distributed among HIPPO, cerebral cortex, lateral septum, ventromedial and arcuate hypothalamic nuclei, with lower levels in 6 additional regions studies. We determined corticosterone (CORT) in brain punches from ADX rats, ADX rats receiving CORT for 5 days, intact rats and intact rats receiving ACTH for 5 days. We correlated (3H)-ligand binding with CORT content in punches obtained from identical brain regions and showed a significant positive correlation in the case of the ADX plus CORT group, for type II corticosteroid receptors. Similarly, a significant correlation emerged with type II sites, when binding capacity was correlated with percentage increases of CORT in brain areas of rats receiving ACTH. It is suggested that in situations where CORT levels are elevated, changes in CORT retention throughout the brain occur as a function of the type II glucocorticoid receptor, although at the level of the HIPPO, both receptors may provide appropriate control of the CNS-pituitary-adrenal axis, according to the physiological or stress levels of circulating hormone.
Assuntos
Encéfalo/metabolismo , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/metabolismo , Adrenalectomia , Aldosterona/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Ligação Competitiva , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Septo Pelúcido/metabolismo , Distribuição Tecidual , Núcleo Hipotalâmico Ventromedial/metabolismoRESUMO
We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6-7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (3H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (approximately equal to 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Corticosterona/sangue , Glutamatos/farmacologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Glutamato de Sódio/farmacologia , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Proteínas de Transporte/sangue , Dexametasona/metabolismo , Dexametasona/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Receptores de Glucocorticoides/metabolismo , Valores de ReferênciaRESUMO
Glucocorticoids (GC) have several known effects on the function of the nervous system, and GC receptors have been identified in regions responding to hormonal action. In the spinal cord, GC receptors have been characterized in vitro, which share several biochemical properties in common with receptors in better studied areas such as the hippocampus. Moreover, enzymes which are induced by GC in the hippocampus, such as glycerolphosphate dehydrogenase and ornithine decarboxylase, are also under specific GC control in the spinal cord. Yet GC receptors in the latter tissue divert from those in hippocampus during some in vivo as well as in vitro studies. In vivo, uptake of [3H]corticosterone by purified cell nuclei was 5-8-fold higher in the hippocampus as compared to the cord. In vitro, a higher percentage of GC receptors previously transformed by heating, showed affinity towards DNA-cellulose in the spinal cord than in the hippocampus. The enzyme RNAse A effectively increased receptor binding to DNA-cellulose in hippocampus, whereas the cord was insensitive to its action. These results suggest that there is a "receptor dysfunction" in the spinal cord, the significance of which is poorly understood in terms of the accepted model of steroid hormone action.