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1.
Pain Physician ; 23(4S): S283-S294, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32942788

RESUMO

BACKGROUND: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown. OBJECTIVES: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI. STUDY DESIGN: A double-blind, parallel-group, randomized controlled trial. SETTING: Pain clinics in a university hospital. METHODS: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used. RESULTS: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P < 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction. LIMITATIONS: There were selection bias and no placebo control. CONCLUSIONS: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids.


Assuntos
Anti-Inflamatórios/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Triancinolona/administração & dosagem , Insuficiência Adrenal/induzido quimicamente , Adulto , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/análise , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Saliva/química , Doenças da Coluna Vertebral/complicações , Doenças da Coluna Vertebral/tratamento farmacológico , Triancinolona/efeitos adversos
2.
Chemosphere ; 258: 127239, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32535440

RESUMO

Alkylphenols (AP) are widespread environmental compounds belonging to the large family of substances known as Endocrine Disrupting Chemicals (EDCs). The present study was carried out to assess the effects of Octylphenol (OP) alone and in combination with Nonylphenol (NP) on the hypothalamus-pituitary-adrenal gland (HPA) axis of the lizard Podarcis sicula. Lizards are good bioindicators due to their features such as wide distribution, large population and good sensitivity to contaminants. Results obtained showed a time and dose-dependent stimulation of the HPA together with a high variation of both catecholamine plasma levels and greater vascularization and hypertrophy of steroidogenic cord of adrenal gland after both OP and OP + NP treatments. Interestingly, the OP + NP mixture treatment has provoked a state of stress of the adrenal gland which in fact appeared to be characterized by the presence of a marked macrophage infiltration which can be seen especially close to the connective capsule surrounding the gland. This macrophage infiltration could be an evidence of a particularly pronounced inflammatory state to indicate, probably, an animal's response to a non-physiological situation.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Lagartos , Fenóis/toxicidade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Glândulas Suprarrenais/imunologia , Glândulas Suprarrenais/fisiologia , Animais , Sistema Hipotálamo-Hipofisário/imunologia , Lagartos/fisiologia , Sistema Hipófise-Suprarrenal/imunologia
3.
Toxicol Lett ; 331: 33-41, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32445661

RESUMO

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.


Assuntos
Dexametasona/toxicidade , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Animais Recém-Nascidos , Arginina Vasopressina/metabolismo , Corticosterona/sangue , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Glutamato Descarboxilase/metabolismo , Sistema Hipotálamo-Hipofisário/embriologia , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Neurônios Aferentes/metabolismo , Núcleo Hipotalâmico Paraventricular/embriologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos
4.
Am J Physiol Endocrinol Metab ; 319(1): E81-E90, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32396496

RESUMO

We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose 17ß-estradiol (E2) treatment, we investigated the association between EPHA7-ephrin (EFN)A5 signaling and E2 negative feedback. Various rat models (OVX, E2-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7. Efna5 was observed strongly expressed in the arcuate nucleus of the female rat by using RNAscope in situ hybridization. Our results indicated that E2, combined with estrogen receptor (ER)α, but not ERß, inhibited Efna5 and gonadotropin-releasing hormone 1 (Gnrh1) expressions in the hypothalamus. In addition, the systemic administration of EPHA7-Fc restrained the inhibition of Efna5 and Gnrh1 by E2, resulting in increased Efna5 and Gnrh1 expressions in the hypothalamus as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E2 negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction.


Assuntos
Efrina-A5/metabolismo , Receptor alfa de Estrogênio/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Hormônio Luteinizante/metabolismo , Precursores de Proteínas/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , Efrina-A5/efeitos dos fármacos , Efrina-A5/genética , Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Retroalimentação Fisiológica/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/efeitos dos fármacos , Hormônio Luteinizante/efeitos dos fármacos , Oligopeptídeos/farmacologia , Ovariectomia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Precursores de Proteínas/efeitos dos fármacos , Ratos , Receptor EphA7/genética , Receptor EphA7/metabolismo , Receptor EphA7/farmacologia , Proteínas Recombinantes
5.
Psychopharmacology (Berl) ; 237(7): 2031-2042, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388622

RESUMO

RATIONALE: Cocaine use disorder (CUD) is associated with dysregulation of the hypothalamic-pituitary-adrenal axis, which plays a critical role in the human stress response. Men and women with CUD differ in reactivity to social stressors. The hypothalamic neuropeptide oxytocin is involved in anxiolytic and natural reward processes, and has shown therapeutic potential for addictive disorders and stress reduction. OBJECTIVES: To examine the impact of oxytocin (oxytocin (OXY) vs. placebo (PBO)) and gender (female (F) vs. male (M)) on response to a social stress task in individuals with CUD. To explore whether ovarian hormones moderate this stress response. METHODS: One hundred twelve adults with CUD were randomized to receive 40 IU intranasal oxytocin (n = 56) or matching placebo (n = 56). Forty minutes after drug administration, participants were exposed to a social stressor. Generalized linear mixed models were used to examine neuroendocrine (cortisol) and subjective (craving, stress) response at pre-stressor, stressor + 0, + 10, + 30, + 60 min. RESULTS: Gender moderated the effect of oxytocin on neuroendocrine response (p = 0.048); women receiving oxytocin (F + OXY) showed blunted cortisol response compared to the other three groups (F + PBO; M + OXY; M + PBO). There was a main effect of gender on subjective stress response; women reported greater stress following the stressor compared to men (p = 0.016). Oxytocin had no significant effect on craving or stress, and gender did not moderate the effect of oxytocin on either measure. Higher endogenous progesterone was associated with lower craving response in women (p = 0.033). CONCLUSIONS: Oxytocin may have differential effects in men and women with CUD. Women may be at greater risk for relapse in response to social stressors, but ovarian hormones may attenuate this effect.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Hormônios Esteroides Gonadais/sangue , Ovário/metabolismo , Ocitocina/administração & dosagem , Caracteres Sexuais , Estresse Psicológico/tratamento farmacológico , Administração Intranasal , Adulto , Transtornos Relacionados ao Uso de Cocaína/sangue , Método Duplo-Cego , Estradiol/sangue , Feminino , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Ovário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Progesterona/sangue , Estresse Psicológico/sangue , Resultado do Tratamento , Adulto Jovem
6.
Psychopharmacology (Berl) ; 237(7): 2187-2199, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32399633

RESUMO

RATIONALE: Dysregulation of the endocannabinoid (eCB) system by high doses of Δ9-tetrahydrocannabinol (THC) is hypothesized to generate a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis contributing to cannabinoid hyperemesis syndrome (CHS). OBJECTIVES AND METHODS: Using the conditioned gaping model of nausea, we aimed to determine if pre-treatments that interfere with stress, or an anti-emetic drug, interfere with THC-induced nausea in male rats. The corticotropin-releasing hormone (CRH) antagonist, antalarmin, was given to inhibit the HPA axis during conditioning. Since eCBs inhibit stress, MJN110 (which elevates 2-arachidonylglycerol (2-AG)) and URB597 (which elevates anandamide (AEA)) were also tested. Propranolol (ß-adrenergic antagonist) and WAY-100635 (5-HT1A antagonist) attenuate HPA activation by cannabinoids and, therefore, were assessed. In humans, CHS symptoms are not alleviated by anti-emetic drugs, such as ondansetron (5-HT3 antagonist); however, benzodiazepines are effective. Therefore, ondansetron and chlordiazepoxide were tested. To determine if HPA activation by THC is dose-dependent, corticosterone (CORT) was analyzed from serum of rats treated with 0.0, 0.5, or 10 mg/kg THC. RESULTS: Antalarmin (10 and 20 mg/kg), MJN110 (10 mg/kg), URB597 (0.3 mg/kg), propranolol (2.5 and 5 mg/kg), WAY-100635 (0.5 mg/kg), and chlordiazepoxide (5 mg/kg) interfered with THC-induced conditioned gaping, but the anti-emetic ondansetron (0.1 and 0.01 mg/kg) did not. THC produced significantly higher CORT levels at 10 mg/kg than at 0.0 and 0.5 mg/kg THC. CONCLUSIONS: Treatments that interfere with the stress response also inhibit THC-induced conditioned gaping, but a typical anti-emetic drug does not, supporting the hypothesis that THC-induced nausea, and CHS, is a result of a dysregulated stress response.


Assuntos
Dronabinol/toxicidade , Endocanabinoides/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Náusea/induzido quimicamente , Náusea/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Animais , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Agonistas de Receptores de Canabinoides/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Náusea/tratamento farmacológico , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
10.
Anticancer Res ; 40(4): 2059-2064, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234897

RESUMO

BACKGROUND/AIM: Prolonged use of glucocorticoids (GC) in glioma treatment can lead to adrenal insufficiency (AI) and subsequent steroid dependence due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This is challenging to diagnose due to its nonspecific clinical symptoms erroneously ascribed to treatment. This study aimed to evaluate the risk factors predisposing patients with gliomas to develop AI. PATIENTS AND METHODS: Charts in the neuro-oncology clinic from July 2018 to March 2019 were reviewed. Inclusion criteria included >18 y/o with WHO Grade II-IV gliomas, and secondary AI. Demographic profile, tumor characteristics, and treatment profile were compared. RESULTS: The majority of patients were started on high dose dexamethasone at >8 mg daily, and were on dexamethasone for 4-8 months. The minimum dose needed to prevent symptoms was 0.5 mg to 2 mg daily. The majority received standard radiation doses ranging from 54-60 Gy. Most patients had radiation exposure to the HPA axis within the prescription isodose levels. CONCLUSION: Prolonged steroid dependency can result from chronic GC use in patients with glioma. Dose and duration of GC are risk factors for its development. Radiation exposure to the HPA axis may also be a contributing factor.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Glioma/tratamento farmacológico , Glucocorticoides/efeitos adversos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/patologia , Adulto , Dexametasona/administração & dosagem , Feminino , Glioma/complicações , Glioma/patologia , Glucocorticoides/administração & dosagem , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/patologia , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/patologia
12.
Clinics (Sao Paulo) ; 75: e1554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32215455

RESUMO

Opioids are the main group of pharmacological agents used during the perioperative period and provide a sedative and analgesic component. The observations of opioid consumption in West Europe indicate that this group of drugs is widely used in chronic noncancer pain therapy. Nearly 20 years ago, the first publications indicating that opioids, as an element of perioperative pharmacotherapy in oncologic patients, increase the risk of tumor recurrence and affect further prognosis were presented. The actual publications suggest that there are multifactorial, complex mechanisms underlying the immunological impact and carcinogenesis promotion of opioids and that the intensity varies depending on the type of opioid. There are also questions about the immunosuppressive effects among patients receiving opioids in the treatment of chronic noncancer pain. The aim of the review article is to present information about the action of opioids on the immune system in carcinogenic settings and to define the clinical usefulness of this pharmacological phenomenon.


Assuntos
Analgésicos Opioides/efeitos adversos , Carcinogênese , Dor Crônica/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Tolerância a Medicamentos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Transtornos Relacionados ao Uso de Opioides , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estudos Retrospectivos
13.
Toxicol Appl Pharmacol ; 394: 114957, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173372

RESUMO

The adverse effects of triphenyltin (TPT) on aquatic systems have attracted much attention because TPT is widely used and prevalent in aquatic environments. Here, zebrafish embryos/larvae were exposed to TPT (0, 0.039, 0.39, and 3.9 nM; 0, 15, 150 and 1500 ng/L) for 7 or 14 days to determine its toxic effects on the hypothalamic-pituitary-thyroid (HPT) axis. The results showed that whole-body total T4 and T3 levels were significantly decreased, which was accompanied by the significant upregulation of the expression of the dio1, dio2 and ugt1ab genes after exposure to TPT for 7 and 14 days. Genes related to thyroid hormone synthesis (crh, tshß, nis, tpo and tg) were upregulated at both 7 and 14 days after TPT exposure. This might have been due to the positive feedback regulation of the HPT axis, which is caused by a decrease in thyroid hormone in the whole body in zebrafish. In addition, the survival rates and body lengths were reduced after treatment with TPT for 7 and 14 days. This indicated that TPT caused adverse effect on the development of zebrafish embryos/larvae. In summary, the results suggested that TPT caused thyroid disruption and developmental toxicity in zebrafish larvae.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Larva/efeitos dos fármacos , Compostos Orgânicos de Estanho/toxicidade , Doenças da Glândula Tireoide/induzido quimicamente , Peixe-Zebra , Animais , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Metamorfose Biológica/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Análise de Sobrevida , Glândula Tireoide/efeitos dos fármacos , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Poluentes Químicos da Água/toxicidade
14.
Cell ; 180(5): 847-861.e15, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32142678

RESUMO

Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.


Assuntos
Infecções Bacterianas/imunologia , Desenvolvimento Embrionário/imunologia , Glucocorticoides/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Dexametasona/farmacologia , Desenvolvimento Embrionário/genética , Feminino , Glucocorticoides/imunologia , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Interleucina-4/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Neoplasias/induzido quimicamente , Neoplasias/genética , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Receptores de Glucocorticoides/genética , Transdução de Sinais/genética
15.
Food Funct ; 11(2): 1235-1244, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32048672

RESUMO

Panaxynol (PAL, also called falcarinol) is widely found in plants of the Umbelliferae family, among which carrots are rich in PAL, so it is proved to be edible. PAL has neuroprotective effects and other pharmacological activities. This study aimed to explore the effects and mechanisms of action of PAL on chronic unpredictable mild stress (CUMS)-induced anxiety and depression in mice. The effects of PAL on behavioral activities in mice were first assessed by a CUMS-induced depression model. The secretion levels of monoamine neurotransmitters and hypothalamic-pituitary-adrenal (HPA) axis-related hormones were measured by ELISA. Western blotting was used to analyze the expression of glucocorticoid receptor (GR), glutamate receptor 1 (GluR1) and synapse-associated protein in the hippocampus. The behavioral experiment results showed that PAL can improve exploratory behavior and activities in mice. Meanwhile, PAL can significantly activate the release of 5-HT/5-HIAA and DA/HVA in the hippocampus. It inhibits the expression of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and corticotrophin-releasing hormone (CRH) in serum and the hypothalamus. The contents of GR, glutamate receptor 1 (GluR1), postsynaptic density-95 (PSD95) and synapsin I protein in the hippocampus significantly increased. Studies have found that PAL can inhibit the hyperfunction of the HPA axis, which may be achieved by regulating HPA axis hormones and GR. Meanwhile, PAL promotes the release of 5-HT and DA in the hippocampus and improves synaptic plasticity in the hippocampus, allowing neurotransmitters to function more effectively. Therefore, PAL may improve anxiety and depression-like effects in mice through the abovementioned effects.


Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Depressão/fisiopatologia , Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Animais , Doença Crônica , Modelos Animais de Doenças , Hipocampo/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurotransmissores/metabolismo , Estresse Psicológico/fisiopatologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
16.
Gen Comp Endocrinol ; 292: 113421, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32032605

RESUMO

The hypothalamic-pituitaryadrenal (HPA) axis is one of the most important physiological mechanisms for mediating life-history trade-offs by reallocating resources to immediate survival from other life-history components during a perturbation. Early-life stressor experience and associated upregulation of glucocorticoids can induce short- and long-term changes to the HPA axis in ways that may optimize survival and/or reproduction for the expected adult environment. Although short-term changes to the HPA axis following perinatal stress are well documented, we know less about the long-term effects of early-life stress especially for non-mammalian wild species. Here, we determined long-term effects of experimental post-natal increases in a circulating glucocorticoid on the HPA axis in a common passerine bird, the house sparrow (Passer domesticus). We manipulated circulating corticosterone in wild, free-living nestlings, transferred fledglings to captivity and assessed corticosterone response to a standardized capture-restraint protocol at the pre-fledging, juvenile, and adult stages. Early-life corticosterone manipulation was associated with depressed baseline and stress-induced concentrations of corticosterone at all stages of life, through adulthood. These results provide rare evidence for the effects of early-life stressor experiences through adulthood, with important implications for understanding developmental programming of an endocrine mediator of life history trade-offs.


Assuntos
Envelhecimento/fisiologia , Corticosterona/farmacologia , Regulação para Baixo/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Pardais/fisiologia , Animais , Corticosterona/sangue , Modelos Biológicos , Estresse Fisiológico/efeitos dos fármacos
17.
Arch. Clin. Psychiatry (Impr.) ; 47(1): 7-12, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088740

RESUMO

Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.


Assuntos
Humanos , Feminino , Adulto , Fator de Necrose Tumoral alfa/sangue , Depressão/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Feminina/psicologia , Placebos/uso terapêutico , Escalas de Graduação Psiquiátrica , Psicometria/métodos , Gravidez/psicologia , Hidrocortisona/sangue , Fertilização In Vitro , Aborto Espontâneo/etiologia , Fluoxetina/uso terapêutico , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Resultado do Tratamento , Depressão/complicações , Depressão/diagnóstico , Infertilidade/etiologia
18.
Sci Rep ; 10(1): 2257, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042019

RESUMO

Depression is a worldwide health problem. In the present study, we found that a dipeptide, tyrosyl leucine (Tyr-Leu, YL), administered orally, intracerebroventricularly, or intraperitoneally exhibited a potent antidepressant-like activity in the forced swim and tail suspension tests in naïve mice. YL increased the amount of cells expressing c-Fos, a marker for neuronal activity, in the dentate gyrus of the hippocampus. YL increased bromo-2'-deoxyuridine-positive cells and doublecortin expression in the dentate gyrus of the hippocampus, suggesting that YL enhanced the proliferation of hippocampal progenitor cells in vivo and in vitro. YL did not affect hippocampal mRNA and protein expression of BDNF, which is a regulatory factor of both neurogenesis and depression-like behavior. Intriguingly, YL suppressed activation of the hypothalamo-pituitary-adrenal axis by forced swim stress. Moreover, other aromatic amino acid-leucines, Phe-Leu and Trp-Leu, also exhibited antidepressant-like activities, suggesting that the structure of aromatic amino acid-leucine may be important for antidepressant activity. In addition, bovine milk casein-derived peptide, Tyr-Leu-Gly (YLG), an anxiolytic peptide, exhibited an antidepressant-like activity. Our findings demonstrate that YL exhibits an antidepressant-like effect, moderates the stress response, and induces hippocampal neuronal proliferation through a signal pathway independent of BDNF.


Assuntos
Antidepressivos , Depressão/tratamento farmacológico , Dipeptídeos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Descoberta de Drogas , Masculino , Camundongos , Oligopeptídeos/uso terapêutico
19.
J Steroid Biochem Mol Biol ; 199: 105605, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31982514

RESUMO

Recent reports described cases of severe hypertension and hypokalemia accompanied by low renin and aldosterone levels during antifungal therapy with posaconazole and itraconazole. These conditions represent characteristics of secondary endocrine hypertension caused by mineralocorticoid excess. Different mechanisms can cause mineralocorticoid excess, including inhibition of the adrenal steroidogenic enzymes CYP17A1 and CYP11B1, inhibition of the peripheral cortisol oxidizing enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) or direct activation of the mineralocorticoid receptor (MR). Compared to previous experiments revealing a threefold more potent inhibition of 11ß-HSD2 by itraconazole than with posaconazole, the current study found sevenfold stronger CYP11B1 inhibition by posaconazole over itraconazole. Both compounds most potently inhibited CYP11B2. The major pharmacologically active itraconazole metabolite hydroxyitraconazole (OHI) resembled the effects of itraconazole but was considerably less active. Molecular modeling calculations assessed the binding of posaconazole, itraconazole and OHI to 11ß-HSD2 and the relevant CYP enzymes, and predicted important interactions not formed by the other systemically used azole antifungals, thus providing an initial explanation for the observed inhibitory activities. Together with available clinical observations, the presented data suggest that itraconazole primarily causes pseudohyperaldosteronism through cortisol-induced MR activation due to 11ß-HSD2 inhibition, and posaconazole by CYP11B1 inhibition and accumulation of the mineralocorticoids 11-deoxycorticosterone and 11-deoxycortisol because of hypothalamus-pituitary-adrenal axis (HPA) feedback activation. Therapeutic drug monitoring and introduction of upper plasma target levels may help preventing the occurrence of drug-induced hypertension and hypokalemia. Furthermore, the systemically used azole antifungals voriconazole, isavuconazole and fluconazole did not affect any of the mineralocorticoid excess targets, offering alternative therapeutic options.


Assuntos
Hiperaldosteronismo/genética , Hipertensão/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/genética , Aldosterona/metabolismo , Animais , Antifúngicos/efeitos adversos , Antifúngicos/farmacologia , Azóis/efeitos adversos , Azóis/metabolismo , Cricetinae , Modelos Animais de Doenças , Monitoramento de Medicamentos , Células HEK293 , Humanos , Hidrocortisona/biossíntese , Hidrocortisona/metabolismo , Hiperaldosteronismo/induzido quimicamente , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/patologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Itraconazol/efeitos adversos , Itraconazol/farmacologia , Mineralocorticoides/farmacologia , Triazóis/efeitos adversos , Triazóis/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-31940232

RESUMO

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period. Exercise is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates glucocorticoid (GC) release, which can alter dietary preferences. Here, we examined the role of the HPA axis and GC signaling in mediating exercise-induced changes in diet preference and the associated neurobiological adaptations that may underlie sex differences in diet choice patterns. Experiment 1 revealed that adrenalectomy did not significantly alter the initiation and persistence of running-induced HF diet avoidance in male rats. Experiment 2 showed that acute WR resulted in greater neural activation than chronic WR in the medial prefrontal (mPFC) and insular cortices (IC) in male rats. Experiment 3 revealed sex differences in the molecular adaptation to exercise and diet preference. First, exercise increased gene expression of fkbp5 in the mPFC, IC, and hippocampus of WR females but had limited influence in males. Second, male and female WR rats that reversed or maintained HF diet avoidance showed distinct sex- and HF diet preference-dependent expression profiles of genes involved in cortical GC signaling (e.g., nr3c1, nr3c2, and src1). Taken together, our results suggest sex differences in region-specific neural adaptations may underlie sex differences in diet preference and the health benefits from exercise.


Assuntos
Glucocorticoides/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Caracteres Sexuais , Animais , Peso Corporal/fisiologia , Dieta Hiperlipídica , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos
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