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1.
PLoS One ; 14(9): e0222340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509580

RESUMO

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.


Assuntos
Hormônio do Crescimento/genética , MicroRNAs/genética , Hormônios Adeno-Hipofisários/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular , Expressão Gênica , Regulação da Expressão Gênica/genética , Hormônio do Crescimento/metabolismo , Masculino , Hipófise/metabolismo , Adeno-Hipófise/metabolismo , Hormônios Adeno-Hipofisários/metabolismo , Cultura Primária de Células , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transfecção
3.
J UOEH ; 41(2): 249-257, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31292372

RESUMO

Here we report a case of a 12-year-old girl who was referred to our department because of marked short stature of more than -5 SD below the median. Although her growth failure began suddenly at 6 years of age, she never had an examination because she had no other symptoms. Brain MRI examination suggested a tumor in the suprasellar region, and endocrine examination revealed combined pituitery hormone deficiency due to the tumor. Before surgery, the supplementation with hydrocortisone and levothyroxine was initiated. The pathological diagnosis of the surgically removed tumor was xanthogranuloma. The pattern of her growth curve showed a growth failure with sudden onset, which is a typical pattern of short stature secondary to pituitary disfunction including growth hormone deficiency associated with brain tumors. This case suggests that growth failure could be the only symptom in pediatric cases with brain tumors. Improved awareness regarding the association of growth failure with brain tumors is needed for earlier diagnosis and treatment. Furthermore, the growth curves should be carefully evaluated in regular health examinations at school.


Assuntos
Estatura , Insuficiência de Crescimento , Transtornos do Crescimento/etiologia , Doenças da Hipófise/complicações , Xantogranuloma Juvenil/complicações , Anormalidades Múltiplas/etiologia , Fatores Etários , Criança , Diagnóstico Precoce , Facies , Feminino , Transtornos do Crescimento/patologia , Transtornos do Crescimento/prevenção & controle , Humanos , Hipotireoidismo/etiologia , Imagem por Ressonância Magnética , Exame Físico , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/patologia , Doenças da Hipófise/cirurgia , Hormônios Adeno-Hipofisários/deficiência , Instituições Acadêmicas , Índice de Gravidade de Doença , Fator de Transcrição Pit-1/deficiência , Xantogranuloma Juvenil/diagnóstico por imagem , Xantogranuloma Juvenil/patologia , Xantogranuloma Juvenil/cirurgia
6.
Thyroid ; 29(4): 502-512, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30747053

RESUMO

BACKGROUND: The secretion of pituitary hormones oscillates throughout the 24-hour period, indicating that circadian clock-mediated mechanisms regulate this process in the gland. Additionally, pituitary hormone synthesis has been shown to be altered in hypo- and hyperthyroidism. Although thyroid hormones can modulate the other peripheral clocks, the interaction between thyroid hormone levels and circadian clock gene expression in the anterior pituitary has yet to be elucidated. METHODS: Male Wistar rats were divided into three groups: control, hypothyroid, and hyperthyroid. Following the experimental procedures, animals were euthanized every three hours over the course of a 24-hour period. The anterior pituitary glands were excised and processed for mRNA expression analysis by quantitative reverse transcriptase polymerase chain reaction. One- and two-way analysis of variance as well as cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene in each experimental group and their interactions. RESULTS: Hyperthyroidism increased the mRNA expression of core clock genes and thyrotrophic embryonic factor (Tef), as well as the mesor and amplitude of brain and muscle Arnt-like protein-1 (Bmal1) and the mesor of nuclear receptor subfamily 1 (Nr1d1) group D member 1, when compared to euthyroid animals. Hypothyroidism disrupted the circadian expression pattern of Bmal1 and period circadian regulator 2 (Per2) and decreased the mesor of Nr1d1 and Tef. Furthermore, it was observed that the pituitary content of Dio2 mRNA was unaltered in hyperthyroidism but substantially elevated in hypothyroidism during the light phase. The upregulated expression was associated with an increased mesor and amplitude, along with an advanced acrophase. The gene expression of all the pituitary hormones was found to be altered in hypo- and hyperthyroidism. Moreover, prolactin (Prl) and luteinizing hormone beta subunit (Lhb) displayed circadian expression patterns in the control group, which were disrupted in both the hypo- and hyperthyroid states. CONCLUSION: Taken together, the data demonstrate that hypo- and hyperthyroidism alter circadian clock gene expression in the anterior pituitary. This suggests that triiodothyronine plays an important role in the regulation of pituitary gland homeostasis, which could ultimately influence the rhythmic synthesis and/or secretion of all the anterior pituitary hormones.


Assuntos
Ritmo Circadiano , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Adeno-Hipófise/metabolismo , Hormônios Adeno-Hipofisários/metabolismo , RNA Mensageiro/metabolismo , Animais , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipertireoidismo/genética , Hipertireoidismo/fisiopatologia , Hipotireoidismo/genética , Hipotireoidismo/fisiopatologia , Masculino , Adeno-Hipófise/fisiopatologia , Hormônios Adeno-Hipofisários/genética , RNA Mensageiro/genética , Ratos Wistar , Tireotropina/sangue , Fatores de Tempo , Transcriptoma , Tri-Iodotironina/sangue
7.
Eur J Med Genet ; 62(11): 103570, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30414530

RESUMO

We report a patient with congenital complex pituitary hormone deficiency (CPHD) with intestinal malrotation and anal atresia. We identified a de novo heterozygous mutation, c.664T > G (p.Cys222Gly), in the FOXA2 gene in this individual. This missense mutation had the potential to affect the DNA binding properties of the FOXA2 protein based on a protein structure prediction. Since a CPHD patient with another missense mutation and one other case with an entire gene deletion have also been reported, we speculated that a haploinsufficiency of the FOXA2 gene might be a genetic etiology for this disorder. Phenotypic similarities and differences among these three cases are also discussed.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Fator 3-beta Nuclear de Hepatócito/genética , Hipotireoidismo/genética , Hormônios Adeno-Hipofisários/deficiência , Fator de Transcrição Pit-1/deficiência , Anormalidades Múltiplas/fisiopatologia , Facies , Heterozigoto , Humanos , Hipotireoidismo/fisiopatologia , Mutação de Sentido Incorreto/genética , Hormônios Adeno-Hipofisários/genética , Conformação Proteica , Fator de Transcrição Pit-1/genética
8.
Rinsho Shinkeigaku ; 58(11): 668-672, 2018 Nov 28.
Artigo em Japonês | MEDLINE | ID: mdl-30369523

RESUMO

A 56-year-old man noted sudden onset of headache, fever, right pupil-spared oculomotor nerve palsy and consciousness disturbance. Swelling of pituitary with T1 high intensity on brain MRI suggested the diagnosis of pituitary apoplexy. Considering significant decrease of pituitary anterior lobe hormone and central diabetes insipidus, high dose of hydrocortisone was administered. Eight days after onset, consciousness level and headache improved. On day 30, brain MRI revealed the reduction of mass size, and on day 46, photophobia and double vision disappeared. Following the rapid response to steroid and disappearance of pituitary lesion, pituitary apoplexy was probably caused by panhypophisitis. Thin-slice brain MRI confirmed the compression of oculomotor nerve at inlet zone of cavernous sinus, suggesting the mechanism of oculomotor palsy was perfusion impairment of feeding artery.


Assuntos
Hipofisite Autoimune/complicações , Imagem por Ressonância Magnética , Síndromes de Compressão Nervosa/diagnóstico por imagem , Síndromes de Compressão Nervosa/etiologia , Nervo Oculomotor/diagnóstico por imagem , Apoplexia Hipofisária/diagnóstico por imagem , Apoplexia Hipofisária/etiologia , Hipofisite Autoimune/tratamento farmacológico , Diabetes Insípido/complicações , Diabetes Insípido/tratamento farmacológico , Humanos , Hidrocortisona/administração & dosagem , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/tratamento farmacológico , Apoplexia Hipofisária/tratamento farmacológico , Hormônios Adeno-Hipofisários/deficiência , Resultado do Tratamento
9.
Endocrinology ; 159(10): 3524-3535, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30020429

RESUMO

More than 60 years ago, Geoffrey Harris described his "neurohumoral theory," in which the regulation of pituitary hormone secretion was a "simple" hierarchal relationship, with the hypothalamus as the controller. In models based on this theory, the electrical activity of hypothalamic neurons determines the release of hypophysiotropic hormones into the portal circulation, and the pituitary simply responds with secretion of a pulse of hormone into the bloodstream. The development of methodologies allowing the monitoring of the activities of members of the hypothalamic-vascular-pituitary unit is increasingly allowing dissection of the mechanisms generating hypothalamic and pituitary pulses. These have revealed that whereas hypothalamic input is required, its role as a driver of pulsatile pituitary hormone secretion varies between pituitary axes. The organization of pituitary cells has a key role in the modification of their response to hypophysiotropic factors that can lead to a memory of previous demand and enhanced function. Feedback can lead to oscillatory hormone output that is independent of pulses of hypophysiotropic factors and instead, results from the temporal relationship between pituitary output and target organ response. Thus, the mechanisms underlying the generation of pulses cannot be generalized, and the circularity of feedforward and feedback interactions must be considered to understand both normal physiological function and pathology. We describe some examples of the clinical implications of recognizing the importance of the pituitary and target organs in pulse generation and suggest avenues for future research in both the short and long term.


Assuntos
Hipotálamo/metabolismo , Neurônios/metabolismo , Hipófise/metabolismo , Hormônios Adeno-Hipofisários/metabolismo , Animais , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Modelos Biológicos , Sistema Hipófise-Suprarrenal/metabolismo
10.
Eur J Endocrinol ; 179(3): R151-R163, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29880706

RESUMO

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.


Assuntos
Hipofisite/diagnóstico , Hipofisite/terapia , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/imunologia , Feminino , Glucocorticoides/uso terapêutico , Histiocitose de Células de Langerhans , Humanos , Hipofisite/etiologia , Imunoglobulina G/imunologia , Imunoterapia/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Hipófise/imunologia , Hipófise/patologia , Hormônios Adeno-Hipofisários/análise , Hormônios Adeno-Hipofisários/deficiência , Gravidez , Complicações na Gravidez , Xantomatose
11.
Zhonghua Nei Ke Za Zhi ; 57(3): 201-205, 2018 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-29518865

RESUMO

Objective: To evaluate the clinical characteristics and etiologies of central diabetes insipidus (CDI). Methods: The clinical data of 230 patients with CDI in the Department of Endocrinology of Chinese PLA General Hospital from 2008 June to 2014 December were collected and analyzed retrospectively. Results: The three most common causes of CDI were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. Among all the CDI, the idiopathic CDI accounted for 37.48%. There were significant differences in age onset and gender distribution among the different causes of CDI. The patients with intracranial germ cell tumors [age of onset(19.2±10.2) years] were younger than the other types of CDI. Germ cell tumors patients were more common in male, and lymphocytic hypophysitis patients were more common in female. The most frequent abnormality of anterior pituitary in patients with CDI was growth hormone deficiency, followed by hypogonadism, adrenal insufficiency and hypothyroidism. The dysfunction of thyroid axis and adrenal axis in patients with germ cell tumor was more common than those in patients with idiopathic and lymphocytic hypophysitis. Conclusions: The most common causes of central diabetes insipidus were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. There were differences in age of onset, gender distribution and abnormal production of anterior pituitary hormones among all causes of CDI patients.


Assuntos
Neoplasias Encefálicas/complicações , Diabetes Insípido Neurogênico/diagnóstico , Hipopituitarismo/complicações , Neoplasias Embrionárias de Células Germinativas/complicações , Hormônios Adeno-Hipofisários/deficiência , Displasia Septo-Óptica/complicações , Distribuição por Idade , Idade de Início , China/epidemiologia , Diabetes Insípido Neurogênico/epidemiologia , Diabetes Insípido Neurogênico/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Distribuição por Sexo
12.
Gynecol Endocrinol ; 34(1): 36-39, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28649890

RESUMO

Ghrelin, an endoggenous for the growth hormone secretagogue receptor, has been shown to participate in the regulation of energy homeostasis and pituitary hormone secretion. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. Ghrelin and obestatin are altered in polycystic ovary syndrome (PCOS), which is characterized by insulin resistance and pituitary hormone secretion disorder. The aim of this study was to evaluate ghrelin/obestatin imbalance in relation to insulin resistance and pituitary hormone in adolescence with PCOS. This restrospective case-control study included 33 adolescence with PCOS and 38 control adolescence. Ghrelin and obestatin concentrations in serum were determined by RIA, and the serum fasting glucose and Insulin were determined by the glucose oxidase color method and INS-EASIA. The serum LH and FSH were measured by highly specific hemiluminescence immunoassays. We found that the serum ghrelin levels and ghrelin/obestatin ratio were significant lower in PCOS group than in control group, and the serum obestatin levels were significant higher in PCOS group than in control group. The ghrelin/obestatin ratios were negatively correlation with LH/FSH ratio and insulin resistant index in PCOS group. The findings of this study suggest that ghrelin/obestatin imbalance may play a role in pathogenesis of adolescent PCOS.


Assuntos
Grelina/sangue , Síndrome do Ovário Policístico/sangue , Anormalidades Múltiplas , Adolescente , Glicemia/análise , Estudos de Casos e Controles , Metabolismo Energético , Facies , Jejum , Feminino , Hormônio Foliculoestimulante/sangue , Homeostase , Humanos , Hipotireoidismo , Insulina/sangue , Resistência à Insulina , Hormônio Luteinizante/sangue , Hormônios Adeno-Hipofisários/deficiência , Hormônios Adeno-Hipofisários/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Estudos Retrospectivos , Fator de Transcrição Pit-1/deficiência , Fator de Transcrição Pit-1/metabolismo
13.
Mol Cell Endocrinol ; 463: 37-48, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-28596131

RESUMO

In anterior pituitary endocrine cells, large (BK), small (SK) and intermediate (IK) conductance calcium activated potassium channels are key determinants in shaping cellular excitability in a cell type- and context-specific manner. Indeed, these channels are targeted by multiple signaling pathways that stimulate or inhibit cellular excitability. BK channels can, paradoxically, both promote electrical bursting as well as terminate bursting and spiking dependent upon intrinsic BK channel properties and proximity to voltage gated calcium channels in somatotrophs, lactotrophs and corticotrophs. In contrast, SK channels are predominantly activated by calcium released from intracellular IP3-sensitive calcium stores and mediate membrane hyperpolarization in cells including gonadotrophs and corticotrophs. IK channels are predominantly expressed in corticotrophs where they limit membrane excitability. A major challenge for the future is to determine the cell-type specific molecular composition of calcium-activated potassium channels and how they control anterior pituitary hormone secretion as well as other calcium-dependent processes.


Assuntos
Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Hormônios Adeno-Hipofisários/fisiologia , Animais , Hormônios/metabolismo , Humanos , Modelos Biológicos , Caracteres Sexuais
14.
Mol Cell Endocrinol ; 463: 49-64, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-28684290

RESUMO

The functions of anterior pituitary cells are controlled by two major groups of hypothalamic and intrapituitary ligands: one exclusively acts on G protein-coupled receptors and the other activates both G protein-coupled receptors and ligand-gated receptor channels. The second group of ligands operates as neurotransmitters in neuronal cells and their receptors are termed as neurotransmitter receptors. Most information about pituitary neurotransmitter receptors was obtained from secretory studies, RT-PCR analyses of mRNA expression and immunohistochemical and biochemical analyses, all of which were performed using a mixed population of pituitary cells. However, recent electrophysiological and imaging experiments have characterized γ-aminobutyric acid-, acetylcholine-, and ATP-activated receptors and channels in single pituitary cell types, expanding this picture and revealing surprising differences in their expression between subtypes of secretory cells and between native and immortalized pituitary cells. The main focus of this review is on the electrophysiological and pharmacological properties of these receptors and their roles in calcium signaling and calcium-controlled hormone secretion.


Assuntos
Hormônios Adeno-Hipofisários/metabolismo , Receptores de Neurotransmissores/metabolismo , Transdução de Sinais , Animais , Linhagem da Célula , Humanos , Ligantes
15.
Cartilage ; 9(1): 63-70, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29219025

RESUMO

Objective Focal chondral defects alter joint mechanics and cause pain and debilitation. Microfracture is a surgical technique used to treat such defects. This technique involves penetration of subchondral bone to release progenitor cells and growth factors from the marrow to promote cartilage regeneration. Often this results in fibrocartilage formation rather than structured hyaline cartilage. Some reports have suggested use of growth hormone (GH) with microfracture to augment cartilage regeneration. Our objective was to test whether intra-articular (IA) GH in conjunction with microfracture, improves cartilage repair in a rabbit chondral defect model. We hypothesized that GH would exhibit a dose-dependent improvement in regeneration. Design Sixteen New Zealand white rabbits received bilateral femoral chondral defects and standardized microfracture repair. One group of animals ( n = 8) received low-dose GH by IA injection in the left knee, and the other group ( n = 8) received high-dose GH in the same manner. All animals received IA injection of saline in the contralateral knee as control. Serum assays, macroscopic grading, and histological analyses were used to assess any improvements in cartilage repair. Results Peripheral serum GH was not elevated postoperatively ( P = 0.21). There was no improvement in macroscopic grading scores among either of the GH dosages ( P = 0.83). Scoring of safranin-O-stained sections showed no improvement in cartilage regeneration and some evidence of increased bone formation in the GH-treated knees. Conclusions Treatment with either low- or high-dose IA GH does not appear to enhance short-term repair in a rabbit chondral defect model.


Assuntos
Doenças das Cartilagens/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Injeções Intra-Articulares/métodos , Articulação do Joelho/efeitos dos fármacos , Animais , Doenças das Cartilagens/patologia , Doenças das Cartilagens/cirurgia , Feminino , Fraturas de Estresse , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/sangue , Humanos , Articulação do Joelho/cirurgia , Modelos Animais , Hormônios Adeno-Hipofisários/uso terapêutico , Período Pós-Operatório , Coelhos
17.
Endocr J ; 64(11): 1063-1071, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-28835591

RESUMO

Dexamethasone-induced Ras-related protein 1 (Rasd1) is a member of the Ras superfamily of monomeric G proteins that have a regulatory function in signal transduction. Here we investigated the role of Rasd1 in regulating estrogen-induced gene expression in primary cultures of rat anterior pituitary cells. Rasd1 mRNA expression in anterior pituitary cells decreased after treatment with forskolin or serum and increased after treatment with 17ß-estradiol (E2). Increases in Rasd1 mRNA expression occurred as early as 0.5 h after E2 treatment, peaked at 1 h and were sustained for as long as 96 h. This rapid and profound increase in Rasd1 mRNA expression induced by E2 was also seen in GH4C1 cells, an estrogen receptor-positive somatolactotroph cell line. Among pituitary estrogen-responsive late genes studied, basal mRNA expression of Pim3 and Igf1 genes was decreased by RNA interference-mediated knockdown of Rasd1 expression, whereas basal expression of the Giot1 gene was increased. Moreover, Rasd1 knockdown enhanced stimulation of Pim3 mRNA expression and attenuated inhibition of Fosl1 mRNA expression 24 h after E2 treatment. These changes in mRNA expression were accompanied by enhanced activity of promoters containing CRE, AP-1 and SRE binding sequences. These results suggest that Rasd1 is an estrogen-responsive immediate early gene and modulates E2 induction of at least several late genes in anterior pituitary cells.


Assuntos
Estradiol/farmacologia , Genes Precoces , Hormônios Adeno-Hipofisários/metabolismo , Proteínas ras/fisiologia , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Precoces/efeitos dos fármacos , Genes Precoces/fisiologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcrição Genética/efeitos dos fármacos , Proteínas ras/genética
18.
PLoS One ; 12(7): e0182495, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28759642

RESUMO

Folliculostellate cell gap junctions establish a network for the transmission of information within the anterior pituitary. Connexins make up gap junction channels. Changes in connexin (Cx) turnover modify gap junction-mediated intercellular communication. We have reported that cytokines and hormones influence Cx43 turnover and coupling in folliculostellate cells and in the folliculostellate cell line TtT/GF. In addition, the expression of different connexins alters intercellular communication and connexins may have functions besides cell coupling. Here we assessed the expression, turnover and subcellular localization of Cx46 and Cx50 in the anterior pituitary and TtT/GF cells. Then, we assessed the impact of various natural (lactation, annual reproductive cycle, bFGF) and pathological (autoimmune orchitis, diabetes/obesity) conditions associated with altered anterior pituitary hormone secretion on Cx46 and Cx50. Anterior pituitary Cx46 and Cx50 expression and subcellular distribution were cell-dependent. Cx46 was expressed by folliculostellate, TtT/GF and endocrine cells. In the cytoplasm, Cx46 was chiefly associated with lysosomes. Variously sized Cx46 molecules were recovered exclusively in the TtT/GF cell nuclear fraction. In the nucleus, Cx46 co-localized with Nopp-140, a nucleolar factor involved in rRNA processing. Neither cytoplasmic nor nuclear Cx46 and Cx43 co-localized. Cx50 localized to folliculostellate and TtT/GF cells, and to the walls of blood capillaries, not to endocrine cells. Cx50 was cytoplasmic and associated with the cell membrane, not nuclear. Cx50 did not co-localize with Cx46 but it co-localized in the cytoplasm and co-immunoprecipitated with Cx43. Cx46 and Cx50 responses to various physiological and pathological challenges were different, often opposite. Cx46 and Cx43 expression and phosphorylation profiles differed in the anterior pituitary, whereas Cx50 and Cx43 were similar. The data suggest that Cx46 participates to cellular growth and proliferation and that Cx50, together with Cx43, contributes to folliculostellate cell coupling.


Assuntos
Conexinas/metabolismo , Adeno-Hipófise/metabolismo , Animais , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Conexinas/genética , Diabetes Mellitus/metabolismo , Células Endócrinas/metabolismo , Células Epiteliais/metabolismo , Feminino , Lactação/metabolismo , Lisossomos/metabolismo , Masculino , Camundongos , Vison , Obesidade/metabolismo , Orquite/metabolismo , Adeno-Hipófise/citologia , Hormônios Adeno-Hipofisários/metabolismo , Reprodução
19.
J Neuroendocrinol ; 29(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28718206

RESUMO

With the aim of studying delta-like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild-type (WT) mice (Dlk1+/+ ) compared to knockout (KO) mice (Dlk1-/- ). The mRNA expression of these molecules was also determined using the reverse transcriptase-polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a higher mRNA expression for growth hormone (GH) receptor and thyroid-stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (-IR), mainly in GH-IR and prolactin (PRL)-IR cells (41.5±3.8%; 13.5±1.7%, respectively). In Dlk1-/- mice, adipocyte cells showed a significant increase in the TSH receptor mRNA expression level. Moreover, the percentage of LEPR-IR GH cells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% of LEP-IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed in WT mice. The results suggest that relationships exist between adipocytes and pituitary GH, PRL and TSH cells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly in PRL cells.


Assuntos
Tecido Adiposo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Hipófise/metabolismo , Animais , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Hormônios Adeno-Hipofisários/metabolismo , Prolactina/metabolismo , RNA Mensageiro/metabolismo , Receptores para Leptina/metabolismo , Receptores da Somatotropina/metabolismo , Receptores da Tireotropina/metabolismo
20.
Clin Med (Lond) ; 17(2): 140-142, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28365624

RESUMO

A 53-year-old woman was diagnosed with hypopituitarism following an acute presentation with cardiac tamponade and hyponatraemia, having recently been investigated for a pericardial effusion. Secondary hypothyroidism is a rare cause of pericardial effusion and tamponade, but an important differential to consider. Management requires appropriate hormone replacement and, critically, a low threshold for commencing stress dose steroids. Clinical signs classically associated with cardiac tamponade are frequently absent in cases of tamponade due to primary and secondary hypothyroidism, and the relatively volume deplete state of secondary hypoadrenalism in hypopituitarism may further mask an evolving tamponade, as the rise in right atrial pressure is less marked even in the presence of large effusion. Our case demonstrates the importance of a high index of suspicion for cardiac tamponade in this patient cohort, even in the absence of clinical signs, and for measuring both thyroid-stimulating hormone and thyroxine levels when evaluating a pericardial effusion.


Assuntos
Hipopituitarismo , Hipotireoidismo , Derrame Pericárdico , Tamponamento Cardíaco , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Humanos , Hiponatremia , Pessoa de Meia-Idade , Hormônios Adeno-Hipofisários
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