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1.
Gen Comp Endocrinol ; 285: 113266, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493394

RESUMO

In the present study, the effects of photic environments, such as background color (white and black) and chromatic lights (blue, green, and red), on body color and gene expressions of melanin-concentrating hormone (mch) in the brain and proopiomelanocortin (pomc) in the pituitary, as well as the roles of the eyes and brain as mediators of ambient light to these genes, were examined in goldfish (Carassius auratus). Body color of goldfish exposed to fluorescent light (FL) under white background (WBG) was paler than those under black background (BBG). Gene expression levels for mch and pomc were reciprocally different depending on background color; under WBG, mRNA levels of mch and pomc were high and low, respectively, while under BBG, these levels were reversed. mch and pomc mRNA expressions of the fish exposed to chromatic light from LED were primarily similar to those exposed to FL, while blue light stimulated the expressions of mch and pomc. Ophthalmectomized goldfish exposed to FL or blue light showed minimum expression levels of mch gene, suggesting that eyes are the major mediator of ambient light for mch gene expression. Contrastingly, mRNA expressions of pomc in ophthalmectomized goldfish exposed to FL were different from those of intact goldfish. These results suggest that eyes play a functional role in mediating ambient light to regulate pomc gene expression. Since ophthalmectomy caused an increase in pomc mRNA contents in the fish exposed to blue light, we suggest that the brain is an additional mediator to regulate pomc gene expression.


Assuntos
Regulação da Expressão Gênica , Carpa Dourada/genética , Hormônios Hipotalâmicos/genética , Luz , Melaninas/genética , Pigmentação/genética , Pigmentação/efeitos da radiação , Hormônios Hipofisários/genética , Pró-Opiomelanocortina/genética , Animais , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Cor , Regulação da Expressão Gênica/efeitos da radiação , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Hipófise/metabolismo , Hipófise/efeitos da radiação , Hormônios Hipofisários/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
2.
BMC Endocr Disord ; 19(1): 138, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829160

RESUMO

BACKGROUND: To evaluate the impact of treatment with recombinant human growth hormone (rhGH; Omnitrope®) on the risk of diabetes mellitus in adults with growth hormone deficiency (GHD), using data from the ongoing PATRO Adults post-marketing surveillance study. METHODS: PATRO Adults is an ongoing post-marketing surveillance study being conducted in hospitals and specialized endocrinology clinics across Europe. All enrolled patients who receive ≥1 dose of Omnitrope® are included in the safety population. Patient profiles, containing all available study database information for each specific patient, were generated for all patients with adverse events (AEs) of diabetes mellitus while participating in the study. Diabetes mellitus was confirmed if fasting plasma glucose was ≥7.0 mmol/L or 2-h plasma glucose ≥11.1 mmol/L during oral glucose tolerance test or glycated hemoglobin ≥6.5%. RESULTS: Up to July 2018, 1293 patients had been enrolled in the study, and 983 (76.0%) remained active. Just under half (n = 687, 49.3%) of the patients were growth hormone (GH) treatment-naïve on entering the study, and most (n = 1128, 87.2%) had multiple pituitary hormone deficiency (MPHD). Diabetes mellitus/inadequate control (worsening) of diabetes mellitus was reported in 21 patients (22 events). The cases were newly diagnosed in 15 patients (age 29-84 years; incidence rate 3.61 per 1000 patient-years) and occurred in 6 patients with pre-existing diabetes mellitus at baseline (age 45-72 years). Most cases of newly diagnosed diabetes mellitus occurred in patients with adult-onset MPHD (n = 13); the remaining cases of new-onset diabetes mellitus occurred in a patient with childhood-onset MPHD who had previously received GH replacement therapy (n = 1), and a patient with adulthood-onset isolated GHD who was naïve to GH replacement therapy (n = 1). All cases of inadequate control/worsening of diabetes mellitus occurred in patients with adult-onset MPHD. CONCLUSIONS: Based on this snapshot of data from PATRO Adults, Omnitrope® treatment is tolerated in adult patients with GHD in a real-life clinical practice setting. No signals of an increased risk for diabetes mellitus have been noted so far, although continued follow-up (both during and after rhGH therapy) is required to confirm this. TRIAL REGISTRATION: Not applicable.


Assuntos
Transtornos do Metabolismo de Glucose/epidemiologia , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos Biossimilares , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Europa (Continente)/epidemiologia , Glucose/metabolismo , Hemoglobina A Glicada/análise , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Hormônios Hipofisários/deficiência , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco
3.
BMC Med Genet ; 20(1): 185, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747893

RESUMO

BACKGROUND: Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA). METHODS: The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method. RESULTS: Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099-0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091-0.575; p = 0.002) were associated with lower odds of occurring an invasive PA. CONCLUSIONS: Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.


Assuntos
Adenoma/genética , Neoplasias Hipofisárias/genética , Sirtuína 1/genética , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Hormônios Hipofisários/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Recidiva
4.
Science ; 365(6459): 1308-1313, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31604241

RESUMO

The neural mechanisms underlying memory regulation during sleep are not yet fully understood. We found that melanin concentrating hormone-producing neurons (MCH neurons) in the hypothalamus actively contribute to forgetting in rapid eye movement (REM) sleep. Hypothalamic MCH neurons densely innervated the dorsal hippocampus. Activation or inhibition of MCH neurons impaired or improved hippocampus-dependent memory, respectively. Activation of MCH nerve terminals in vitro reduced firing of hippocampal pyramidal neurons by increasing inhibitory inputs. Wake- and REM sleep-active MCH neurons were distinct populations that were randomly distributed in the hypothalamus. REM sleep state-dependent inhibition of MCH neurons impaired hippocampus-dependent memory without affecting sleep architecture or quality. REM sleep-active MCH neurons in the hypothalamus are thus involved in active forgetting in the hippocampus.


Assuntos
Hipocampo/citologia , Hormônios Hipotalâmicos/fisiologia , Melaninas/fisiologia , Memória , Hormônios Hipofisários/fisiologia , Células Piramidais/fisiologia , Sono REM , Animais , Comportamento Animal , Hipocampo/fisiologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
5.
Nat Commun ; 10(1): 4923, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664021

RESUMO

Behavioral impulsivity is common in various psychiatric and metabolic disorders. Here we identify a hypothalamus to telencephalon neural pathway for regulating impulsivity involving communication from melanin-concentrating hormone (MCH)-expressing lateral hypothalamic neurons to the ventral hippocampus subregion (vHP). Results show that both site-specific upregulation (pharmacological or chemogenetic) and chronic downregulation (RNA interference) of MCH communication to the vHP increases impulsive responding in rats, indicating that perturbing this system in either direction elevates impulsivity. Furthermore, these effects are not secondary to either impaired timing accuracy, altered activity, or increased food motivation, consistent with a specific role for vHP MCH signaling in the regulation of impulse control. Results from additional functional connectivity and neural pathway tracing analyses implicate the nucleus accumbens as a putative downstream target of vHP MCH1 receptor-expressing neurons. Collectively, these data reveal a specific neural circuit that regulates impulsivity and provide evidence of a novel function for MCH on behavior.


Assuntos
Hipocampo/metabolismo , Região Hipotalâmica Lateral/metabolismo , Hormônios Hipotalâmicos/metabolismo , Comportamento Impulsivo , Melaninas/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Hormônios Hipotalâmicos/genética , Masculino , Melaninas/genética , Vias Neurais , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Hormônios Hipofisários/genética , Ratos , Ratos Sprague-Dawley , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo
6.
Int J Mol Sci ; 20(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623386

RESUMO

This study aimed to examine the effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) on Aquaporin 5 (AQP5) expression in granulosa (Gc) and theca cells (Tc) from medium (MF) and large (LF) ovarian follicles of pigs. The results showed that GH significantly decreased the expression of AQP5 in Gc from MF in relation to the control. In the Gc of large follicles, PRL stimulated the expression of AQP5. However, the increased expression of AQP5 in the Tc of LF was indicated by GH and PRL in relation to the control. A significantly higher expression of the AQP5 protein in the Gc from MF and LF was indicated by FSH and PRL. In co-cultures, an increased expression of AQP5 was observed in the Gc from LF incubated with LH, PRL, and GH. A significantly increased expression of AQP5 was also observed in co-cultures of Tc from all type of follicles incubated with LH, whereas PRL stimulated the expression of AQP5 in Tc from MF. Moreover, AQP5 protein expression increased in the co-culture isolated from MF and LF after treatment with FSH, LH, PRL, and GH. AQP5 immunoreactivity was observed in the cytoplasm, mainly in the perinuclear region and endosomes, as well as in the cell membranes of Gc and Tc from the LF and MF.


Assuntos
Aquaporina 5/genética , Regulação da Expressão Gênica de Plantas , Folículo Ovariano/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Biomarcadores , Técnicas de Cocultura , Feminino , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Hormônio do Crescimento/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Prolactina/metabolismo , Suínos , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismo
7.
J Assoc Physicians India ; 67(10): 29-32, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571448

RESUMO

Background: Data on pituitary Magnetic Resonance Imaging (MRI) in patients with abnormal pituitary hormones in Saudi Arabia are very scarce. Objective: To define the frequency of normal pituitary MRI in patients with abnormal pituitary hormones in a well-defined population. Design: Retrospective analysis of radiological and hormonal data of patients with pituitary MRI between January 2008 and December 2015. Settings: Departments of Endocrinology and Radiology at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia. Patients: 459 patients with clinical, hormonal and radiological data. Main outcome measures: The frequency of normal pituitary MRI in patients with abnormal pituitary hormones. Results: Over the 7-year period, Out of 459 patients; 129 (28.1 %) were males and 330 (71.9 %) were females with mean age of 35.4 ± 13.7. Positive MRI compared to normal MRI were seen in 268 (58.4 %) and 191 (41.6 %) subjects respectively. Subjects with Positive MRI were significantly older, 36.8 ± 14.1 vs. 33.5 ± 12.9, p value=0.01. Hyperfunctiong pituitary hormones were significantly associated with positive MRI, 259 (63.2%) vs. 151 (36.8) where as hypofunctiong pituitary hormones were associate with normal MRI, 40 (81.6%) vs. 9 (18.4%), p value < 0.001. Females with hyperfunctioning pituitary hormones were significantly associated with positive MRI whereas males with hyporfunctioning pituitary hormones were significantly associated with normal MRI. Three types of hyperfunctioning pituitary gland were seen such as hyperprolactinemia, somatotroph adenoma, and corticotroph adenoma were associated with more frequent positive MRI as to Five types of hypofunctioning pituitary gland were seen such as panhypopituitarism, secondary hypogonadism, growth hormone deficiency, central hypothyroidism and central adrenal insufficiency which were associated with more frequent normal MRI. Conclusion: The current study indicates hyperfunctioning pituitary gland was significantly associated with positive MR whereas hypofunctioning pituitary gland was associate with normal MRI. In the absence of registry data, larger cooperative studies involving diverse population samples from multiple centers could help to provide further information on the true frequency nationally. Limitations: Question of clustering of cases within the study region and limited study sample size.


Assuntos
Hipófise , Hormônios Hipofisários , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estudos Retrospectivos , Arábia Saudita
8.
Diabetes ; 68(12): 2210-2222, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31530579

RESUMO

Melanin-concentrating hormone (MCH) is an important regulator of food intake, glucose metabolism, and adiposity. However, the mechanisms mediating these actions remain largely unknown. We used pharmacological and genetic approaches to show that the sirtuin 1 (SIRT1)/FoxO1 signaling pathway in the hypothalamic arcuate nucleus (ARC) mediates MCH-induced feeding, adiposity, and glucose intolerance. MCH reduces proopiomelanocortin (POMC) neuronal activity, and the SIRT1/FoxO1 pathway regulates the inhibitory effect of MCH on POMC expression. Remarkably, the metabolic actions of MCH are compromised in mice lacking SIRT1 specifically in POMC neurons. Of note, the actions of MCH are independent of agouti-related peptide (AgRP) neurons because inhibition of γ-aminobutyric acid receptor in the ARC did not prevent the orexigenic action of MCH, and the hypophagic effect of MCH silencing was maintained after chemogenetic stimulation of AgRP neurons. Central SIRT1 is required for MCH-induced weight gain through its actions on the sympathetic nervous system. The central MCH knockdown causes hypophagia and weight loss in diet-induced obese wild-type mice; however, these effects were abolished in mice overexpressing SIRT1 fed a high-fat diet. These data reveal the neuronal basis for the effects of MCH on food intake, body weight, and glucose metabolism and highlight the relevance of SIRT1/FoxO1 pathway in obesity.


Assuntos
Adiposidade/efeitos dos fármacos , Proteína Forkhead Box O1/metabolismo , Intolerância à Glucose/metabolismo , Hiperfagia/metabolismo , Hormônios Hipotalâmicos/farmacologia , Melaninas/farmacologia , Neurônios/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Pró-Opiomelanocortina/metabolismo , Sirtuína 1/metabolismo , Adiposidade/fisiologia , Animais , Proteína Forkhead Box O1/genética , Intolerância à Glucose/genética , Hiperfagia/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Técnicas de Patch-Clamp , Ratos Sprague-Dawley , Sirtuína 1/genética
9.
World Neurosurg ; 132: e802-e811, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31404693

RESUMO

OBJECTIVE: Surgical treatment of large and giant pituitary adenomas is challenging and associated with higher risk of complications and lower rate of gross total resection. We present our experience with surgical management of large and giant adenomas using the extended endoscopic transsphenoidal approach (EETA). METHODS: A total of 80 patients with large (30-39 mm) and giant (≥40 mm) pituitary adenomas who underwent tumor resection using EETA were studied. Radiologic data, hormonal and visual status, surgical outcomes, complications, and factors affecting the extent of resection were evaluated. RESULTS: Forty-five tumors (56.3%) were classified as large and 35 (43.8%) as giant adenomas. Gross total resection was achieved in 66 patients (82.5%), near-total resection in 10 (12.5%), and subtotal resection in 4 (5%). Preoperative factors including larger tumor size, multilobular shape of tumor, and higher Knosp scores significantly decrease the likelihood of gross total resection. Of patients with preoperative visual acuity impairment and visual field deficit, 76.8% and 74.1%, respectively, experienced improvement after surgery. The most common complications include new pituitary insufficiency (16.4%), permanent diabetes insipidus (7.5%), and cerebrospinal fluid leakage (5%). Two cases of meningitis (2.5%) and 3 deaths (3.8%) occurred in this cohort of patients. Mean follow-up duration was 24.2 months. CONCLUSIONS: EETA can be a safe and efficient approach as the first-line treatment of patients with large and giant pituitary adenomas and is associated with high rates of gross total resection or near-total resection, visual function improvement, and a relatively low rate of complications.


Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Cavidade Nasal/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Oriente Médio , Hormônios Hipofisários/sangue , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Osso Esfenoide/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Transtornos da Visão/etiologia , Adulto Jovem
10.
Proc Natl Acad Sci U S A ; 116(34): 17061-17070, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31375626

RESUMO

Hypocretin/orexin (HCRT) and melanin concentrating hormone (MCH) neuropeptides are exclusively produced by the lateral hypothalamus and play important roles in sleep, metabolism, reward, and motivation. Loss of HCRT (ligands or receptors) causes the sleep disorder narcolepsy with cataplexy in humans and in animal models. How these neuropeptides are produced and involved in diverse functions remain unknown. Here, we developed methods to sort and purify HCRT and MCH neurons from the mouse late embryonic hypothalamus. RNA sequencing revealed key factors of fate determination for HCRT (Peg3, Ahr1, Six6, Nr2f2, and Prrx1) and MCH (Lmx1, Gbx2, and Peg3) neurons. Loss of Peg3 in mice significantly reduces HCRT and MCH cell numbers, while knock-down of a Peg3 ortholog in zebrafish completely abolishes their expression, resulting in a 2-fold increase in sleep amount. We also found that loss of HCRT neurons in Hcrt-ataxin-3 mice results in a specific 50% decrease in another orexigenic neuropeptide, QRFP, that might explain the metabolic syndrome in narcolepsy. The transcriptome results were used to develop protocols for the production of HCRT and MCH neurons from induced pluripotent stem cells and ascorbic acid was found necessary for HCRT and BMP7 for MCH cell differentiation. Our results provide a platform to understand the development and expression of HCRT and MCH and their multiple functions in health and disease.


Assuntos
Hormônios Hipotalâmicos/metabolismo , Hipotálamo/metabolismo , Melaninas/metabolismo , Neurônios/metabolismo , Orexinas/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Hormônios Hipotalâmicos/genética , Hipotálamo/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Melaninas/genética , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Orexinas/genética , Hormônios Hipofisários/genética
11.
Cells ; 8(8)2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412674

RESUMO

In mammals, the tachykinin 3 (TAC3)/tachykinin receptor 3 (TACR3) systems have been confirmed to play an important role in the regulation of puberty onset. Using grass carp pituitary cells as the model, our recent study found that the TAC3 gene products could significantly induce somatolactin α (SLα) synthesis and secretion via TACR3 activation. In the present study, we seek to examine if pituitary TACR3 can serve as a regulatory target and contribute to TAC3 interactions with other SLα regulators. Firstly, grass carp TACR3 was cloned and tissue distribution showed that it could be highly detected in grass carp pituitary. Using HEK293 cells as the model, functional expression also revealed that grass carp TACR3 exhibited ligand binding selectivity and post-receptor signaling highly comparable to its mammalian counterpart. Using grass carp pituitary cells as the model, TACR3 mRNA expression could be stimulated by insulin-like growth factor (IGF)-I and -II via the IGF-I receptor coupled to phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Interestingly, IGF-I/-II cotreatment could also significantly enhance TAC3-induced SLα mRNA expression and the potentiating effect was dependent on TACR3 expression and activation of adenylate cyclase (AC)/cAMP/protein kinase A (PKA), phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3)/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/calmodulin-dependent protein kinase II (CaMK-II) cascades. Besides, IGF-I-induced Akt phosphorylation but not MEK, extracellular signal-regulated kinase (ERK1/2), and P38MAPK phosphorylation was notably enhanced by TACR3 activation. These results, as a whole, suggest that the potentiating effect of IGFs on TAC3 gene products-induced SLα mRNA expression was mediated by TACR3 upregulation and functional crosstalk of post-receptor signaling in the pituitary.


Assuntos
Carpas/crescimento & desenvolvimento , Proteínas de Peixes/metabolismo , Neurocinina B/metabolismo , Hipófise/efeitos dos fármacos , Hormônios Hipofisários/metabolismo , Receptores da Neurocinina-3/metabolismo , Maturidade Sexual/fisiologia , Somatomedinas/farmacologia , Animais , Carpas/metabolismo , Proteínas de Peixes/fisiologia , Células HEK293 , Humanos , Hipófise/citologia , Hipófise/metabolismo , Receptores da Neurocinina-3/genética , Desenvolvimento Sexual/fisiologia , Maturidade Sexual/efeitos dos fármacos , Transdução de Sinais
12.
Nature ; 571(7764): 198-204, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292557

RESUMO

Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.


Assuntos
Neurônios/fisiologia , Sono/fisiologia , Peixe-Zebra/fisiologia , Animais , Evolução Biológica , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Epêndima/citologia , Movimentos Oculares , Fluorescência , Frequência Cardíaca , Hipnóticos e Sedativos/farmacologia , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Neurônios/efeitos dos fármacos , Pigmentação/fisiologia , Hormônios Hipofisários/metabolismo , Polissonografia/métodos , Sono/efeitos dos fármacos , Privação do Sono/fisiopatologia , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Sono de Ondas Lentas/efeitos dos fármacos , Sono de Ondas Lentas/fisiologia
13.
Curr Biol ; 29(13): R644-R646, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287986

RESUMO

REM sleep is a paradoxical state accompanied by suspended thermoregulation that is preferentially expressed under optimal ambient temperatures. Komagata and colleagues now demonstrate that activity in hypothalamic melanin concentrating hormone neurons is essential for the temperature-dependent modulation of REM sleep.


Assuntos
Neurobiologia , Sono REM , Hormônios Hipotalâmicos , Melaninas , Neurônios , Hormônios Hipofisários , Temperatura
14.
Medicina (B Aires) ; 79(3): 191-196, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284253

RESUMO

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.


Assuntos
Adenoma/terapia , Neoplasias Hipofisárias/terapia , Adenoma/diagnóstico , Adenoma/mortalidade , Adenoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos Transversais , Feminino , Humanos , Masculino , Hormônios Hipofisários , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
15.
Reprod Biol Endocrinol ; 17(1): 49, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234873

RESUMO

BACKGROUND: Superovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels? METHODS: One leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis. RESULTS: A total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle. CONCLUSIONS: Cell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.


Assuntos
Líquido Folicular/metabolismo , Gonadotropinas/farmacologia , Células da Granulosa/metabolismo , Hormônios Hipofisários/metabolismo , Transcriptoma/efeitos dos fármacos , Androstenodiona/metabolismo , Estradiol/metabolismo , Feminino , Fertilização In Vitro , Hormônio Foliculoestimulante/metabolismo , Ontologia Genética , Humanos , Hormônio Luteinizante/metabolismo , Transdução de Sinais/genética , Testosterona/metabolismo
16.
Nat Commun ; 10(1): 2505, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175285

RESUMO

Brain signals that govern memory formation remain incompletely identified. The hypothalamus is implicated in memory disorders, but how its rapidly changing activity shapes memorization is unknown. During encounters with objects, hypothalamic melanin-concentrating hormone (MCH) neurons emit brief signals that reflect object novelty. Here we show that targeted optogenetic silencing of these signals, performed selectively during the initial object encounters (i.e. memory acquisition), prevents future recognition of the objects. We identify an upstream inhibitory microcircuit from hypothalamic GAD65 neurons to MCH neurons, which constrains the memory-promoting MCH cell bursts. Finally, we demonstrate that silencing the GAD65 cells during object memory acquisition improves future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that object-associated signals in genetically distinct but interconnected hypothalamic neurons differentially control whether the brain forms object memories. This gating of memory formation by hypothalamic activity establishes appropriate behavioral responses to novel and familiar objects.


Assuntos
Glutamato Descarboxilase/metabolismo , Hormônios Hipotalâmicos/metabolismo , Hipotálamo/fisiologia , Melaninas/metabolismo , Memória/fisiologia , Neurônios/metabolismo , Hormônios Hipofisários/metabolismo , Receptores do Hormônio Hipofisário/metabolismo , Reconhecimento Psicológico/fisiologia , Animais , Hipotálamo/citologia , Hipotálamo/metabolismo , Memória/efeitos dos fármacos , Camundongos , Inibição Neural/fisiologia , Vias Neurais , Optogenética , Piperidinas/farmacologia , Receptores do Hormônio Hipofisário/antagonistas & inibidores , Reconhecimento Psicológico/efeitos dos fármacos
17.
Mol Neurobiol ; 56(12): 8076-8086, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31183806

RESUMO

Melanin-concentrating hormone (MCH) is a highly conserved neuropeptide known to exhibit important functions in the brain. Some studies have reported that MCH improves memory by promoting memory retention. However, the precise molecular mechanisms by which MCH enhances memory impairment have yet to be fully elucidated. In this study, MCH was administered to the scopolamine-induced memory-impaired mice via the nasal cavity to examine the acute effects of MCH and Alzheimer's disease (AD) mouse models to evaluate the chronic effects of MCH. MCH improved memory impairment in both models and reduced soluble amyloid beta in the cerebral cortex of APP/PS1 transgenic mice. In vitro assays also showed that MCH inhibits amyloid beta-induced cytotoxicity. Furthermore, MCH increased long-term potentiation (LTP) in the hippocampus of wild-type and 5XFAD AD mouse model. To further elucidate the mechanisms of the chronic effect of MCH, the levels of phosphorylated CREB and GSK3ß, and the expression of BDNF, TrkB and PSD95 were examined in the cerebral cortex and hippocampus. Our findings indicate that MCH might have neuroprotective effects via downstream pathways associated with the enhancement of neuronal synapses and LTP. This suggests a therapeutic potential of MCH for the treatment of neurodegenerative diseases such as AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Modelos Animais de Doenças , Hormônios Hipotalâmicos/administração & dosagem , Melaninas/administração & dosagem , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Hormônios Hipofisários/administração & dosagem , Administração Intranasal , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/metabolismo , Gravidez
18.
Neurochem Res ; 44(7): 1736-1744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037609

RESUMO

Recent advances in human induced pluripotent stem cells (hiPSCs) offer new possibilities for biomedical research and clinical applications. Neurons differentiated from hiPSCs may be promising tools to develop novel treatment methods for various neurological diseases. However, the detailed process underlying functional maturation of hiPSC-derived neurons remains poorly understood. Here, we analyze the developmental architecture of hiPSC-derived cortical neurons, iCell GlutaNeurons, focusing on the primary cilium, a single sensory organelle that protrudes from the surface of most growth-arrested vertebrate cells. To characterize the neuronal cilia, cells were cultured for various periods and evaluated immunohistochemically by co-staining with antibodies against ciliary markers Arl13b and MAP2. Primary cilia were detected in neurons within days, and their prevalence and length increased with increasing days in culture. Treatment with the mood stabilizer lithium led to primary cilia length elongation, while treatment with the orexigenic neuropeptide melanin-concentrating hormone caused cilia length shortening in iCell GlutaNeurons. The present findings suggest that iCell GlutaNeurons develop neuronal primary cilia together with the signaling machinery for regulation of cilia length. Our approach to the primary cilium as a cellular antenna can be useful for both assessment of neuronal maturation and validation of pharmaceutical agents in hiPSC-derived neurons.


Assuntos
Cílios/metabolismo , Cílios/ultraestrutura , Células-Tronco Pluripotentes Induzidas/citologia , Neurônios/citologia , Fatores de Ribosilação do ADP/imunologia , Adenilil Ciclases/imunologia , Animais , Anticorpos/imunologia , Linhagem Celular , Cílios/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Hormônios Hipotalâmicos/farmacologia , Imuno-Histoquímica , Lítio/farmacologia , Melaninas/farmacologia , Proteínas Associadas aos Microtúbulos/imunologia , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Ratos Wistar , Receptores de Somatostatina/imunologia
19.
Endocr Res ; 44(4): 153-158, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30966827

RESUMO

Objective: Pituitary hormones are critical for bone development and maturation. It is currently unknown whether congenital multiple pituitary hormone deficiency (CMPHD) is associated with osteonecrosis of femoral head (ONFH). Methods: Clinical presentations and hormonal profiles of three patients with CMPHD and ONFH were retrospectively described. The incidence of ONFH in this population was studied. Results: (1) Congenital hypopituitarism was diagnosed in three patients. Femoral epiphyseal fusion in these patients was markedly delayed, and they had very low bone mineral density. (2) Hip pain, which is the main presentation of ONFH, occurred at the age of 20-30 years. ONFH induced by excessive glucocorticoids was excluded. (3) The estimated incidence of ONFH was approximately 694:100,000. Conclusions: CMPHD, especially a lack of growth and sex hormones, may contribute to ONFH.


Assuntos
Necrose da Cabeça do Fêmur/complicações , Hipopituitarismo/congênito , Hipopituitarismo/complicações , Hormônios Hipofisários/deficiência , Adulto , Feminino , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/patologia , Humanos , Hipopituitarismo/patologia , Masculino , Estudos Retrospectivos , Adulto Jovem
20.
BMJ Case Rep ; 12(4)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015250

RESUMO

Joubert syndrome (JS) and JS-related disorders are a group of developmental delay, multiple congenital anomalies and complex midbrain-hindbrain malformations. A few cases of JS with multiple pituitary hormone deficiency (MPHD) have been reported in literature. Here, we presented an unusual presentation of JS in a newborn with MPHD. This case is intended to draw attention to the rare association of JS and MDPH by increasing the awareness of this syndrome.


Assuntos
Cerebelo/anormalidades , Anormalidades do Olho/complicações , Terapia de Reposição Hormonal/métodos , Doenças Renais Císticas/complicações , Hormônios Hipofisários/deficiência , Retina/anormalidades , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/genética , Assistência ao Convalescente , Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/genética , Diagnóstico Diferencial , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/tratamento farmacológico , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/etiologia , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Recém-Nascido , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Pênis/anormalidades , Hormônios Hipofisários/metabolismo , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Resultado do Tratamento
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