RESUMEN
Galanin is a peptide widely distributed in the hypothalamic-pituitary axis. In the female rat pituitary, galanin is mainly present in lactotrophs, where it regulates their secretion and proliferation. Galanin expression is increased in oestrogen-induced prolactinomas, and it has been proposed that oestrogen effects on lactotroph function and proliferation could be mediated by galanin. Previous studies from our laboratory demonstrated that the synthetic progestin levonorgestrel antagonizes pituitary tumorigenesis of rats given oestrogen, reducing the number of proliferating cells and increasing cell death by nonapoptotic mechanism(s). To elucidate the role of galanin in levonorgestrel effects on the tumours, we examined galanin and prolactin mRNA and peptide expression in prolactinomas of rats receiving the progestin. Levonorgestrel reduced the pituitary weight and serum prolactin concentrations in oestrogen-treated rats. Galanin mRNA expression (determined by in situ hybridization), and the number of galanin expressing cells (determined by immunocytochemistry) were also reduced by the progestin in tumour-bearing rats. However, neither prolactin mRNA content, nor the number of prolactin-expressing cells, were modified by levonorgestrel treatment of oestrogen-receiving rats. The present study suggests that levonorgestrel controls pituitary growth by diminishing galanin expression. In contrast, changes in serum prolactin concentration seem to be more related to the reduction in tumour size, since the reduction in galanin expression was not large enough to regulate prolactin mRNA expression or the percentage of lactotrophs.
Asunto(s)
Dietilestilbestrol , Galanina/genética , Levonorgestrel/farmacología , Neoplasias Hipofisarias/metabolismo , Congéneres de la Progesterona/farmacología , Prolactina/genética , Animales , Recuento de Células , Femenino , Galanina/análisis , Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Hibridación in Situ , Tamaño de los Órganos/efectos de los fármacos , Ovariectomía , Hipófisis/patología , Neoplasias Hipofisarias/inducido químicamente , Neoplasias Hipofisarias/patología , Prolactina/análisis , Prolactina/sangre , ARN Mensajero/análisis , Ratas , Ratas Endogámicas F344RESUMEN
Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in female than in male rats. To investigate gender differences in DES-induced pituitary tumor formation, we employed female and male rats and neonatally androgenized females, which received 100 microg of testosterone propionate (TP) after birth. At 3 months of age, all rats were deprived of their gonads and divided into control and DES-treated groups. Forty days after beginning treatment, control pituitary weight and serum PRL were similar in gonadectomized males (GDX), ovariectomized females (OVX) and androgenized-ovariectomized females (OVX + TP), but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold higher in OVX + DES than in GDX + DES or OXV + TP + DES (p<0.001). At the pituitary level, nuclear estrogen receptors (NE(2)R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE(2)R were lower in OVX + DES (101.3+/-9.0 fmol/mg DNA) than in GDX + DES (174.6 +/-16.8; p<0.05) and in OXV + DES + TP (150.3+/-27.7; p<0.05). A similar profile was found for cytosolic progestin receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a cell subpopulation with refractory secretory response and a few gonadotropes. In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized female rats on one side and male and TP-androgenized females on the other, may by due in part to heterogeneity of cell populations. Our data further suggest that neonatal hypothalamic exposure to androgens, as in normal males or androgenized females with masculinization of hypothalamic centers, may condition the response to DES stimulation later in life.
Asunto(s)
Carcinógenos/toxicidad , Dietilestilbestrol/toxicidad , Neoplasias Hipofisarias/inducido químicamente , Neoplasias Hipofisarias/patología , Prolactina/metabolismo , Prolactinoma/inducido químicamente , Prolactinoma/patología , Animales , Citosol/metabolismo , Dietilestilbestrol/sangre , Femenino , Masculino , Microscopía Electrónica , Orquiectomía , Tamaño de los Órganos/fisiología , Ovariectomía , Neoplasias Hipofisarias/metabolismo , Prolactina/sangre , Prolactinoma/metabolismo , Ratas , Ratas Endogámicas F344 , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Esteroides/metabolismo , Caracteres SexualesRESUMEN
The aim of our work was to evaluate the effect of a chronic (22 days) administration of corticosterone, which induces supraphysiological serum levels of the hormone, on an inhibitory avoidance learning in rats (one-trial step-through learning task, footshock: 0.5 mA, 2 s). We also studied hippocampal markers of neuroanatomical CA3 pyramidal neuron atrophy by using the Golgi staining method. Chronic exposure to high CORT serum levels induced a significant impairment of inhibitory avoidance learning. The CORT group also showed hippocampal glucocorticoid receptor (GR) downregulation and the decrease of hippocampal CA3 branch points and total dendritic length in the apical tree that would be causally related with the learning impairment.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Corticosterona/toxicidad , Células Piramidales/efectos de los fármacos , Células Piramidales/patología , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/patología , Animales , Atrofia , Peso Corporal/efectos de los fármacos , Corticosterona/administración & dosificación , Corticosterona/sangre , Citosol/metabolismo , Dendritas/efectos de los fármacos , Dendritas/patología , Dexametasona/metabolismo , Implantes de Medicamentos , Técnicas In Vitro , Masculino , Tamaño de los Órganos/efectos de los fármacos , Células Piramidales/fisiopatología , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/metabolismoRESUMEN
The Wobbler mouse, a model of amyotrophic lateral sclerosis (ALS), presents motorneuron degeneration and pronounced astrogliosis in the spinal cord. We have studied factors controlling astrocyte proliferation in cultures derived from Wobbler and control mice spinal cord. Basal rate of [3H]thymidine incorporation was 15 times lower in Wobbler astrocytes. While in control cultured cells interleukin-1alpha (IL-1) and corticosterone (CORT) significantly increased proliferation, both agents were inactive in Wobbler astrocytes. The lack of response to CORT was not due to the absence of glucocorticoid receptors, because similar receptor amounts were found in Wobbler and control astrocytes. In contrast to IL-1 and CORT, transforming growth factor-beta1 (TGF-beta1) substantially increased proliferation of Wobbler astrocytes but not of control cells. Differences in response to TGF-beta1 were also obtained by measuring glial fibrillary acidic protein (GFAP) immunoreaction intensity, which was substantially higher in Wobbler astrocytes. Thus, abnormal responses to different mitogens characterized Wobbler astrocytes in culture. We suggest that TGF-beta1 may play a role in the reactive gliosis and GFAP hyperexpression found in the degenerating spinal cord of this model of ALS.
Asunto(s)
Astrocitos/metabolismo , Receptores de Glucocorticoides/metabolismo , Médula Espinal/metabolismo , Animales , Astrocitos/citología , Astrocitos/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Corticosterona/farmacología , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/genética , Gliosis/patología , Interleucina-1/farmacología , Cinética , Masculino , Ratones , Ratones Endogámicos , Ratones Mutantes Neurológicos , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/patología , Fármacos Neuroprotectores/farmacología , Pregnatrienos/farmacología , Valores de Referencia , Médula Espinal/citología , Médula Espinal/efectos de los fármacos , Timidina/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Mineralocorticoids play a predominant role in development of salt appetite and hypertension. Since vasoactive peptides could mediate the central effects of mineralocorticoids, we evaluated changes of immunoreactive (IR) arginine vasopressin (AVP) in the paraventricular (PVN) and supraoptic (SON) hypothalamic nucleus during DOCA-induced salt appetite. In one model, rats having free access to water and 3% NaCl during 9 (prehypertensive stage) or 21 days (hypertensive stage) received DOCA (s.c., 10 mg/rat/in alternate days). A decrease in the IR cell area, number of IR cells and staining intensity was obtained in magnocellular PVN of rats treated during 9 days. After 21 days IR cell area and number of cells in the PVN also decreased, but staining intensity of remaining cells was normal. The same parameters were unchanged in the SON. In another model, animals treated with DOCA during 9 days had only access to 3% NaCl or water. The IR cell area in PVN and SON significantly increased in mineralocorticoid-treated and control animals, both drinking 3% NaCl. Staining intensity (PVN and SON) and number of IR cells (PVN) also augmented in DOCA-treated animals drinking salt respect of a group drinking water. Plasma AVP in rats treated with DOCA and offered salt and water, exhibited a 2-2.5 fold increase at the time of salt appetite induction. Plasma AVP was substantially higher in rats drinking salt only, while the highest levels were present in salt-drinking DOCA-treated rats. Thus, peptide depletion in the PVN may be due to increased release, because reduced levels of hypothalamic and posterior pituitary AVP were measured in this model. In rats drinking salt only the substantial increase of IR AVP in the PVN and SON, may be due to dehydration and hyperosmosis. Because DOCA-salt treated rats showed higher AVP levels in the PVN compared to untreated rats drinking salt only, it is possible that DOCA sensitized PVN cells to increase AVP production. The results suggest the vasopressinergic system could mediate some central functions of mineralocorticoids.
Asunto(s)
Apetito/efectos de los fármacos , Desoxicorticosterona/farmacología , Hipotálamo/metabolismo , Cloruro de Sodio Dietético , Vasopresinas/metabolismo , Animales , Inmunohistoquímica , Masculino , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Vasopresinas/sangreRESUMEN
Aging is associated with a disturbance in the regulation of the hypothalamic-pituitary-adrenal axis (HPA) and reduced levels of glucocorticoid receptors (GR) in the hippocampus. To compensate for these effects, we have investigated whether estrogen therapy normalized the HPA response to stress and GR in hippocampus and paraventricular (PVN) nucleus. Young (3-4 months) and old (20 months) male Sprague-Dawley rats were bled by tail cut in the basal state and following ether stress. While basal and ether-stimulated levels of plasma corticosterone (CORT) were similar in the two groups, old animals presented a delayed termination of the response to ether stress. A dexamethasone inhibition test carried out in old animals, showed a failure to completely block plasma CORT after ether stimulation. Furthermore, in old rats GR-immunoreactive levels were reduced in CA1-CA2 hippocampal subfields and subiculum, while normal levels were obtained in CA3-CA4 and PVN. We observed that prolonged estrogen treatment (6 weeks) of old rats normalized the termination of the stress response, restored dexamethasone inhibition of plasma CORT, and increased GR immunoreactivity in CA1 and CA2 hippocampal subfields and subiculum. The results suggest that estrogen treatment enhanced the glucocorticoid feedback signal by increasing GR in hippocampus, and corrected the disturbances in HPA axis regulation. These animal experiments may be important to elucidate the effects of estrogenic on the hippocampal and HPA dysfunction associated with aging and Alzheimer's disease in humans.
Asunto(s)
Glándulas Suprarrenales/efectos de los fármacos , Estradiol/farmacología , Hipotálamo/efectos de los fármacos , Hipófisis/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Estrés Fisiológico/fisiopatología , Glándulas Suprarrenales/fisiopatología , Envejecimiento/fisiología , Animales , Corticosterona/sangre , Éter , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipotálamo/fisiopatología , Cinética , Masculino , Tamaño de los Órganos , Hipófisis/fisiopatología , Ratas , Ratas Sprague-Dawley , Estrés Fisiológico/inducido químicamenteRESUMEN
Glucocorticoids (GC) and mineralocorticoids (MC) have profound regulatory effects upon the central nervous system (CNS). Hormonal regulation affects several molecules essential to CNS function. First, evidences are presented that mRNA expression of the alpha3 and beta1-subunits of the Na,K-ATPase are increased by GC and physiological doses of MC in a region-dependent manner. Instead, high MC doses reduce the beta1 isoform and enzyme activity in amygdaloid and hypothalamic nuclei, an effect which may be related to MC control of salt appetite. The alpha3-subunit mRNA of the Na,K-ATPase is also stimulated by GC in motoneurons of the injured spinal cord, suggesting a role for the enzyme in GC neuroprotection. Second, we provide evidences for hormonal effects on the expression of mRNA for the neuropeptide arginine vasopressin (AVP). Our data show that GC inhibition of AVP mRNA levels in the paraventricular nucleus is sex-hormone dependent. This sexual dimorphism may explain sex differences in the hypothalamic-pituitary-adrenal axis function between female and male rats. Third, steroid effects on the astrocyte marker glial fibrillary acidic protein (GFAP) points to a complex regulatory mechanism. In an animal model of neurodegeneration (the Wobbler mouse) showing pronounced astrogliosis of the spinal cord, in vivo GC treatment down-regulated GFAP immunoreactivity, whereas the membrane-active steroid antioxidant U-74389F up-regulated this protein. It is likely that variations in GFAP protein expression affect spinal cord neurodegeneration in Wobbler mice. Fourth, an interaction between neurotrophins and GC is shown in the injured rat spinal cord. In this model, intensive GC treatment increases immunoreactive low affinity nerve growth factor (NGF) receptor in motoneuron processes. Because GC also increases immunoreactive NGF, this mechanism would support trophism and regeneration in damaged tissues. In conclusion, evidences show that some molecules regulated by adrenal steroids in neurons and glial cells are not only involved in physiological control, but additionally, may play important roles in neuropathology.
Asunto(s)
Corticoesteroides/farmacología , Encéfalo/efectos de los fármacos , Regulación de la Expresión Génica , Médula Espinal/efectos de los fármacos , Animales , Arginina Vasopresina/biosíntesis , Femenino , Proteína Ácida Fibrilar de la Glía/biosíntesis , Masculino , Ratas , Caracteres Sexuales , ATPasa Intercambiadora de Sodio-Potasio/biosíntesisRESUMEN
The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been implicated in the genesis of hypertension due to deoxycorticosterone acetate (DOCA)-salt treatment of uninephrectomized rats. In this work, we studied if DOCA treatment of intact rats in doses arousing a salt appetite (a prehypertensive state), modulated mRNA for AVP and OT in the hypothalamus. Male Sprague-Dawley rats were offered both tap water and 3% NaCl in separate bottles and received vehicle or subcutaneous injections of 10 mg DOCA on alternate days for 7 days (4 injections) or 17 days (9 injections). They developed a preference for 3% NaCl solutions 24-48 h after treatment. Brain slices from rats killed on the 8th or 18th day were exposed to 35S-labeled probes encoding prepro-AVP mRNA or OT mRNA, respectively. Expression of these mRNAs was measured in the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN) and magnocellular cells of the supraoptic nucleus (SON). No changes were obtained in neuropeptide mRNA levels in the parvocellular division of the PVN between control and the two groups of DOCA-treated rats. However, DOCA-treated animals presented an increased number of grains per cell for AVP mRNA in the magnocellular division of the PVN and in magnocellular cells of the SON, as shown by group mean comparisons and frequency histograms. No changes were detected for OT mRNA. In a second series of studies, control or DOCA-treated rats were offered 3% NaCl or water as the only choice. Animals drinking 3% NaCl showed increased AVP and OT mRNA levels, whether they received DOCA or not. However, AVP mRNA levels in both nuclei were higher in DOCA-treated rats drinking 3% NaCl than in controls drinking salt solution. In comparison, control and DOCA-treated rats drinking water showed lower levels of AVP mRNA. OT mRNA levels in the SON remained unchanged in the same groups. The results suggest that in the magnocellular cells of the PVN and SON, increments in AVP mRNA are obtained following increments in salt intake produced by either mineralocorticoid treatment or exclusive salt drinking. In rats offered salt solution and water to drink, DOCA effects on AVP mRNA developed before changes occurred in serum sodium levels. Because combined DOCA + salt treatment induced a higher response in terms of AVP mRNA expression, we suggest that AVP could be a target of the central effects of the mineralocorticoid.
Asunto(s)
Apetito/efectos de los fármacos , Arginina Vasopresina/genética , Desoxicorticosterona/farmacología , Cloruro de Sodio/farmacología , Glándulas Suprarrenales/fisiología , Animales , Ingestión de Líquidos/fisiología , Expresión Génica/fisiología , Hipertensión/fisiopatología , Hibridación in Situ , Masculino , Concentración Osmolar , Oxitocina/genética , Núcleo Hipotalámico Paraventricular/química , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/química , Núcleo Supraóptico/efectos de los fármacos , Núcleo Supraóptico/metabolismoRESUMEN
Astrocytes participate in central nervous system injury, degenerative diseases and also perform macrophagic functions. The present work investigates: 1) the effect of the physiological glucocorticoid corticosterone (CORT) and the synthetic agonist dexamethasone (DEX) on latex beads phagocytosis by neonatal rat cortical astrocytes in culture, and 2) the expression of immunoreactive glucocorticoid receptors (GR) in astrocytes cultured in different media with or without a pulse application of CORT. The results indicated that glucocorticoids reduced astrocyte phagocytic activity, as occurred with macrophages, independently of the culturing conditions employed. The extent of phagocytosis was inversely related to nuclear immunostaining for GR in cultures in fetal calf serum, which contained endogenous glucocorticoid. However, no correlation was found between nuclear GR and phagocytosis for cultures in glucocorticoid-free medium or in medium containing CORT. It is suggested that additional factors, besides the GR, may be involved in glucocorticoid modulation of astrocyte phagocytosis.
Asunto(s)
Antiinflamatorios/farmacología , Astrocitos/inmunología , Corticosterona/farmacología , Dexametasona/farmacología , Glucocorticoides/farmacología , Fagocitosis/efectos de los fármacos , Animales , Astrocitos/química , Astrocitos/citología , Células Cultivadas , Corteza Cerebral/citología , Fagocitosis/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/análisis , Receptores de Glucocorticoides/metabolismoRESUMEN
We have studied glucocorticoid receptors (GR) and actions in the spinal cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of circulating corticosterone (CORT) were increased in Wobbler mice. Single point binding assays showed that cytosolic type II GR in the spinal cord of Wobbler mice of both sexes were slightly reduced compared with normal littermates. Saturation analysis further demonstrated a non-significant reduction in Bmax with increased Kd. In the hippocampus, however, we found down-regulation of GR, a probable response to increased CORT levels. We also found that the basal activity of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was higher in Wobbler mice than in control animals. Both groups showed a two-fold stimulation of ODC activity after treatment with dexamethasone (DEX). Additionally, Wobbler mice presented with an intense proliferation of astrocytes immunoreactive (ir) for glial fibrillary acidic protein (GFAP) in grey and white matter of the spinal cord. The enhanced GFAP-ir was attenuated after four days of treatment with a corticosterone (CORT) pellet implant, producing a pharmacological increase in peripheral circulating CORT. Taking into consideration the content of GR and the changes in ODC activity and GFAP-ir brought about by glucocorticoids, we suggest that Wobbler mice are hormone responsive. Further elucidation of glucocorticoid effects in this model may be relevant for understanding the possible use of hormones in human neurodegenerative diseases.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Dexametasona/metabolismo , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/metabolismo , Médula Espinal/metabolismo , Atrofias Musculares Espinales de la Infancia/metabolismo , Animales , Astrocitos/citología , División Celular , Corticosterona/sangre , Modelos Animales de Enfermedad , Femenino , Proteína Ácida Fibrilar de la Glía/análisis , Región Lumbosacra , Masculino , Ratones , Ratones Mutantes , Cuello , Ornitina Descarboxilasa/análisis , Factores Sexuales , Médula Espinal/enzimología , Médula Espinal/patologíaRESUMEN
1. Arginine vasopressin (AVP) is synthesized in specific brain regions including the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN). Whereas magnocellular AVP responds to osmotic stimuli and functions mainly--although not exclusively--as an antidiuretic hormone, that produced in the parvocellular region controls the hypothalamus-pituitary-adrenal (HPA) axis, in conjunction with CRF. 2. In view of the reported sex differences in control of the HPA axis, we studied if these also pertain to AVP mRNA in the PVN of ovariectomized-estrogenized female rats and male rats determined by in situ hybridization. AVP mRNA was measured in intact rats, adrenalectomized (ADX) rats and ADX receiving dexamethasone (DEX) of both sexes. 3. Computerized autoradiography showed that in both sexes, AVP mRNA levels in the parvocellular division of the PVN increased after adrenalectomy and decreased following DEX. However, the reduction by DEX was more pronounced in female rats. No changes were found for the magnocellular region. Grain counting analysis of the medial-medial (MMP) and medial-lateral (MLP) subdivisions of the parvocellular region showed that the average number of grains per cell area in the MMP region of adrenally intact female rats was higher than that in males. However, in females there was no clear-cut effect of adrenalectomy on AVP mRNA levels, although the reduction after DEX treatment was again greater than that in male rats. Frequency histograms constructed by plotting the number of cells vs the number of grains per area substantiated the enhanced glucocorticoid negative control of AVP mRNA in the MMP and MLP of female rats. 4. The results indicated a sexual dimorphism in the glucocorticoid-dependent plasticity of AVP mRNA levels in the PVN. Because AVP mRNA expression differs between sexes under basal levels, after adrenalectomy, and after DEX treatment, these plastic changes may differentially condition the response to stress. Taking into consideration that stress and AVP may play a role in neurogenic hypertension, the possibility of sexual dimorphisms in AVP control may be important to assess the role of sex hormones in stress and steroid-derived hypertension.
Asunto(s)
Arginina Vasopresina/genética , Glucocorticoides/fisiología , Núcleo Hipotalámico Paraventricular/fisiología , Caracteres Sexuales , Animales , Densitometría , Femenino , Expresión Génica/fisiología , Masculino , Ovariectomía , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
It is known that chronic exposure of F344 rats to diethylstilbestrol (DES) induces prolactin (PRL)-secreting pituitary tumors composed of proliferating mammotropic cells. In the present work, we studied the effects of progesterone (P4) on several parameters stimulated in the pituitary tumors (DES-T), such as nuclear estrogen receptors (NE2R), cytosolic progestin receptors (CP4R) and serum PRL. Additionally, we have measured in hypothalamus the mRNA levels for tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of dopamine, the main PRL-inhibitory factor. We found that pellet implantation of P4 during 1 month significantly reduced weight, ligand binding to NE2R and CP4R and serum PRL in the tumorous glands. Reductions in sex steroid receptor binding were due to changes in Bmax without changes in Kd, as observed after Scatchard plot analysis. Receptor binding data, therefore, suggests a pituitary site of action of P4. TH mRNA expression was studied in tuberoinfundibular dopaminergic (TIDA) neurons by in situ hybridization techniques employing a 35S-labeled oligonucleotide probe. Mean number of grains/cell decreased significantly in DES-T, an effect partly reversed by P4 treatment. Frequency histograms were constructed by plotting the number of cells versus the number of grains/cell and examined by x2 test and analysis of residuals. We found that DES-T presented significantly more cells with less grains whereas in control glands, P4-treated rats and DES-T receiving P4, cells with a higher grain number prevailed. These results suggest that in addition to a direct pituitary effect, P4 may also antagonize DES-induced tumorigenesis acting on mRNA for TH and presumably on the activity of TIDA neurons of the hypothalamus. The use of DES-T as a model for hyperprolactinemia may allow further assessment of P4 effects in pituitary adenomas in humans.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Hipofisarias/tratamiento farmacológico , Progesterona/farmacología , Receptores de Estrógenos/efectos de los fármacos , Tirosina 3-Monooxigenasa/efectos de los fármacos , Animales , Unión Competitiva , Dietilestilbestrol/farmacología , Femenino , Hibridación in Situ , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas F344RESUMEN
We have previously reported that estrogen treatment of steroid-free, ovariectomized-adrenalectomized (OVX-ADX) rats, increased binding to glucocorticoid type II receptors (GR) in some brain regions. The present report studied the effects of estradiol in OVX-ADX rats receiving chronic corticosterone (CORT) treatment. Using binding assays, GR was reduced by CORT replacement in cytosol of hippocampus and septum, but not in whole hypothalamus. GR were recovered after 4 days of estradiol therapy. Using Mab7, a monoclonal antibody against the activated nuclear form of GR, we observed that estrogen treatment increased immunoreactivity measured by computerized densitometry in areas targeted by glucocorticoids. Significantly higher staining for GR developed in CA1 and CA2 hippocampal subfields, paraventricular nucleus of the hypothalamus and lateral ventral septal nuclei of estradiol-receiving, CORT-treated OVX-ADX rats. The amplification of the glucocorticoid biological signal by female sex hormones, may thus affect several neuroendocrine parameters and the outcome of stress-related diseases.
Asunto(s)
Encéfalo/metabolismo , Estradiol/farmacología , Receptores de Glucocorticoides/metabolismo , Adrenalectomía , Animales , Anticuerpos Monoclonales , Encéfalo/efectos de los fármacos , Corticosterona/farmacología , Densitometría , Regulación hacia Abajo/efectos de los fármacos , Femenino , Glucocorticoides/metabolismo , Técnicas para Inmunoenzimas , Ovariectomía , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/efectos de los fármacosRESUMEN
A avaliaçäo nutricional subjectiva global (ANSG), introduzida por Destsky et al. (1987), avalia a perda de peso corpóreo, gordura e massa muscular e mudanças na ingestäi dietética, sendo eficaz para o diagnóstico de desnutriçäo protéico-calórica do adulto hospitalizado. OBJETIVO. Comparar a eficiência do emprego da ANSG em nosso meio, com as medidas tradicionais de avaliaçäo nutricional (antropometria, exames laboratoriais e testes cutâneos de hipersensibilidade tardia). MÉTODO. Realizou-se um estudo prospectivo em 100 pacientes do hospital da Beneficiência Portuguesa de Säo Paulo. Admitidos consecutivamente em 3/91 a 5/91. Comparou-se a aplicaçäo do questionário sistematizado por Destky et al (1987), com as medidas antropométricas (peso e altura corporais, prega cutânea truciptal e circunferência do braço) e bioquímica (albumina sérica, hemoglobina, hematócrito e linfócitos de sangue periférico). A ANSG e avaliaçäo antropométrica foram realizadas pela mesma, observadora (LZC), treinada e capacitada para essa funçäo. RESULTADOS. Dos 100 pacientes avaliados pela ANSG, 83 por cento foram categorizados como normais, 14 por cento desnutridos moderados e 3 por cento desnutridos graves. Observaram-se associaçöes estatisticamente significantes (p<0,05) entre albumina (<3,5), hemoglobina (<13,9g/mL), prega cutânea triciptal (<10mm) e circunferência muscular do braço (<23,3cm) com a presença de desnutriçäo moderada e grave estabelecidas pela ANSG. O diagnóstico de suporte nutricional enteral e parenteral...
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Evaluación Nutricional , Antropometría , Estado Nutricional , Desnutrición Proteico-Calórica/diagnóstico , Nutrición Enteral , Nutrición ParenteralRESUMEN
OBJECTIVE: Nutritional Assessment methods (ONA) are traditionally employed in hospitalized patients (anthropometry, laboratorial exams and immunological tests). The Subjective Global Assessment (SGA) estimates weight loss and changes in dietetic intake as being allegedly efficient for protein-caloric malnutrition diagnosis of the hospitalized adult. PURPOSE: Compare the efficacy of SGA against the traditional ONA. METHODS: The prospective study was done with 100 hospitalized patients from 3/90-5/90 at the Hospital Beneficência Portuguesa de São Paulo. The Detsky et al. questionnaire was applied besides anthropometric measurements (body weight, triceps skinfold thickness-TSF, mirdam circumference MCA) and laboratorial examinations (serun albumin, hemoglobin, peripheral blood lymphocytes) all of them in the first 3 days of admission. SGA always preceded ONA, and was always done by the same observer. RESULTS: There was a significant reduction on the average values of anthropometric and laboratorial measurements with the progressive worsening of nutritional status assessed by SGA. There were significant associations (p < 0.05) between hypoalbuminemia (< 3.5 g/dL) loss of TSF (< 10 mm) and MAC (< 23.3 cm) in those patients classified as moderately and severely malnourished by SGA (14%). Hypoalbuminemia, low TSF and SGA malnutrition were all significantly associated to mortality (p < 0.05). CONCLUSION: SGA in our hospital is a reliable diagnostic method for the diagnosis of malnutrition of hospitalized adult patients and malnutrition of hospitalized adult patients and keeps prognostic association with mortality.
Asunto(s)
Evaluación Nutricional , Adulto , Antropometría , Nutrición Enteral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Nutrición Parenteral , Desnutrición Proteico-Calórica/diagnósticoRESUMEN
Existen controversias acerca de la eficiencia del uso exclusivo de aminoácidos esenciales en nutrición parenteral (NPT) para pacientes con insuficiencia renal aguda. Para estudiar el impacto sobre la insuficiencia renal, en pacientes post cirugía cardíaca, fueron randomizados los pacientes en la unidad de terapia intensiva divididos en dos grupos. Grupo AE con 17 pacientes en NPT con solo aminoácidos esensiales y el grupo AT con 17 pacientes en NPT con aminoácidos esenciales y no esenciales. La NPT fue dada en promedio por 10 días. Los pacientes dializados tuvieron menor recuperación de la función renal y mortalidad mas alta (p<0.05). En conclusión la NPT con AE en insuficiencia renal aguda no modificó los niveles de urea y creatina y tasa de mortalidad, cuando se comparó con la NPT con mezcla completa de aminoácidos.(AU)
Asunto(s)
Humanos , Lesión Renal Aguda/complicaciones , Nutrición Parenteral , Cirugía Torácica , Aminoácidos EsencialesRESUMEN
Existen controversias acerca de la eficiencia del uso exclusivo de aminoácidos esenciales en nutrición parenteral (NPT) para pacientes con insuficiencia renal aguda. Para estudiar el impacto sobre la insuficiencia renal, en pacientes post cirugía cardíaca, fueron randomizados los pacientes en la unidad de terapia intensiva divididos en dos grupos. Grupo AE con 17 pacientes en NPT con solo aminoácidos esensiales y el grupo AT con 17 pacientes en NPT con aminoácidos esenciales y no esenciales. La NPT fue dada en promedio por 10 días. Los pacientes dializados tuvieron menor recuperación de la función renal y mortalidad mas alta (p<0.05). En conclusión la NPT con AE en insuficiencia renal aguda no modificó los niveles de urea y creatina y tasa de mortalidad, cuando se comparó con la NPT con mezcla completa de aminoácidos.
Asunto(s)
Humanos , Lesión Renal Aguda/complicaciones , Nutrición Parenteral , Cirugía Torácica , Aminoácidos EsencialesRESUMEN
We previously reported a reduction of glucocorticoid receptors (GCR) in diethylstilbestrol-induced pituitary tumors (DES-T) in rats. Presently, we found that bromocriptine (BROM) treatment increased the levels of GCR in DES-T, demonstrated by steroid binding assays and immunocytochemistry using a monoclonal antibody against the type II GCR. We also found that the high content of nuclear estradiol receptors in the adenomata and the elevated levels of PRL in serum of DES-T were significantly reduced after BROM treatment. In parallel studies, PRL secretion was measured after administration of ether stress. In controls, serum PRL markedly increased after ether and this effect was blunted by prior dexamethasone (DEX) administration, due to the steroid negative feedback on PRL secretion. In animals with DES-T, ether stress had no effect on serum PRL, and the inhibition by DEX was lost unless they received BROM, which restored the negative feedback of DEX on serum PRL. Although increases of PRL titers in pituitary tumors may be due to estrogenic stimulation of lactotroph proliferation and function, coupled to absent dopaminergic inhibition on these cells, other mechanisms are possible. In this respect, inefficient steroid negative feedback on PRL synthesis due to down-regulation of GCR may contribute to hyperprolactinemia. This mechanism is supported from the restoration of GCR and steroid negative feedback on serum PRL by treatment of tumor-bearing rats with BROM.
Asunto(s)
Bromocriptina/farmacología , Dietilestilbestrol , Glucocorticoides/farmacología , Neoplasias Hipofisarias/fisiopatología , Prolactina/metabolismo , Receptores de Glucocorticoides/metabolismo , Animales , Anticuerpos Monoclonales , Dexametasona/metabolismo , Dexametasona/farmacología , Retroalimentación , Técnicas para Inmunoenzimas , Masculino , Adenohipófisis/efectos de los fármacos , Adenohipófisis/metabolismo , Neoplasias Hipofisarias/inducido químicamente , Ratas , Receptores de Glucocorticoides/efectos de los fármacosRESUMEN
1. Studies were performed to determine the changes in immunoreactive (IR) type II glucocorticoid receptors of the ventral horn of the spinal cord produced by adrenalectomy (ADX), dexamethasone (DEX) treatment, and spinal cord transection in rats. 2. These treatments did not significantly affect the number of IR neurons of the ventral horn; however, staining intensity was enhanced after ADX and decreased following 4 days of DEX. A similar response pattern was observed for glial-type cells. 3. In control rats, about half of the ventral horn motoneurons were surrounded by immunoreactive glial perineuronal cells. These perineuronal cells increased after ADX (77% of counted neurons) and decreased following DEX treatment (32%; P < 0.05). 4. Two days after transection, staining was intensified in ventral horn motoneurons and glial cells located in the spinal cord below the lesion. Immunoreactive perineuronal cells increased to 85% of counted neurons, from a value of 66% in sham-operated rats (P < 0.05). 5. These findings suggest considerable plasticity of the spinal cord GCR in response to changes in hormonal levels and experimental lesions. It is possible that factors involved in cell to cell communication with transfer of hypothetical regulatory molecules may play roles in GCR regulation and the increased immunoreaction of glia associated with neurons following transection and ADX.
Asunto(s)
Adrenalectomía , Dexametasona/farmacología , Neuronas/metabolismo , Receptores de Glucocorticoides/metabolismo , Médula Espinal/metabolismo , Análisis de Varianza , Animales , Inmunohistoquímica , Masculino , Neuronas Motoras/citología , Neuronas Motoras/efectos de los fármacos , Neuroglía/citología , Neuroglía/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Glucocorticoides/análisis , Receptores de Glucocorticoides/efectos de los fármacos , Valores de Referencia , Médula Espinal/fisiologíaRESUMEN
Fifty-two patients with AIDS-IV C (opportunistic infections) received nutritional supplementation, (enteral diets or total parenteral nutrition) in 60 admission episodes. Most patients had lost more than 10% of their ideal weight; albumin serum level was inferior or equal to 3.0 g/dl at admission in 33.3% of cases, and low serum albumin had a positive correlation with mortality (p less than 0.05%). Lean body mass, indirectly evaluated by 24 hour urinary creatinine excretion was less than 30% of the ideal in 44.7% of cases, and had a positive correlation with death rate. Enteral nutrition was given in 16.7% of episodes, total parenteral nutrition in 35% and in the remaining episodes the patient received only oral supplements. Patients that received TPN spent more time in hospital than patients with enteral nutrition (23.1 more or less 21.3 days against 7.2 more or less 4.8 days). Patients with AIDS IV C are usually undernourished, have low serum albumin and important deficit of lean body mass. Weight loss and low lean body mass are associated positively with mortality. Nutritional support had no influence on mortality rate.