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1.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334740

RESUMO

Myasthenia gravis (MG) is a rare and potentially dangerous autoimmune condition, which affects the acetylcholine receptors at the neuromuscular junction of skeletal muscle. MG's diverse symptomatology may readily masquerade as other neurological conditions, posing a diagnostic challenge to clinicians. We describe a 24-year old man who presented to the emergency department with a new onset internuclear ophthalmoplegia. After a series of investigations, we eventually arrived at a diagnosis of MG with pseudointernuclear ophthalmoplegia with an incidentally detected prolactinoma. We explore the literature regarding the pathophysiology of pseudointernuclear ophthalmoplegia, the link between prolactin and autoimmunity and the association between prolactinoma and MG.


Assuntos
Diplopia/etiologia , Miastenia Gravis/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Humanos , Achados Incidentais , Masculino , Miastenia Gravis/complicações , Miastenia Gravis/imunologia , Transtornos da Motilidade Ocular/diagnóstico , Hipófise/diagnóstico por imagem , Hipófise/metabolismo , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/complicações , Prolactina/sangue , Prolactina/metabolismo , Prolactinoma/sangue , Prolactinoma/complicações , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Medicine (Baltimore) ; 99(38): e22239, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957368

RESUMO

BACKGROUND: Prolactin (PRL), an inflammatory hormone with cytokine properties, has long been considered to play a crucial role in the pathogenesis of autoimmune diseases, including systemic sclerosis (SSc). However, the plasma/serum levels of PRL in SSc were inconsistent in published studies. The aim of this study was to evaluate the plasma/serum levels of PRL in patients with SSc accurately. METHODS: Electronic databases, including PubMed, EMBASE, Cochrane Library, CNKI, VIP and WANFANG databases, were searched up to October 15, 2019. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effects model analysis. All statistical analyses were conducted with STATA 12.0. RESULTS: Fifty three articles were obtained after searching databases, and 9 studies with 293 SSc patients and 282 controls were finally included. The meta-analysis showed that the plasma/serum PRL level in SSC patients was significantly increased compared with the healthy controls, with the SMD of 1.00 and 95% CI (0.56, 1.43). Subgroup analysis showed that female patients had higher plasma/serum PRL levels. However, no significant change in plasma/serum PRL levels was observed in male patients (P = .318). In subgroup analysis by detection type, electrochemiluminescence immunoassay (ECLIA) group and enzyme-linked immunosorbent assay (ELISA) group showed higher PRL levels among SSc patients. CONCLUSIONS: In summary, our meta-analysis showed a significantly higher plasma/serum PRL level in SSc patients than healthy controls, and it was associated with gender and detection method.


Assuntos
Prolactina/metabolismo , Escleroderma Sistêmico/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Medições Luminescentes , Masculino , Fatores Sexuais
3.
Eur J Endocrinol ; 183(3): C11-C13, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508315

RESUMO

There can potentially be a number of clinical interactions that could adversely affect patient outcomes in a patient with a prolactinoma and psychiatric disease that might require antipsychotic and dopamine agonist treatment. Dopamine agonists stimulate the dopamine D2 receptor, resulting in a decrease in prolactin (PRL) levels and in prolactinoma size but action on dopamine receptors in the meso-limbic system may rarely cause psychosis and more commonly cause impulse control disorders. The psychiatric benefits of antipsychotic agents involve blocking the D2 and other dopamine receptors but this blockade often also causes hyperprolactinemia. In patients with macroprolactinomas and psychosis, observation, estrogen/progestin replacement, and surgery can be considered in addition to dopamine agonists. In those who require dopamine agonists for PRL and tumor size control, the introduction of antipsychotics may blunt this effect, so that higher doses of the dopamine agonists may be needed. Alternatively, antipsychotics that have less of a blocking effect at the D2 receptor, such as aripiprazole, can be tried, if appropriate. For patients already on antipsychotic drugs who are found to have a macroprolactinoma for which dopamine agonists are required, dopamine agonists can be initiated at low dose and the dose escalated slowly. However, such patients require careful monitoring of psychiatric status to avoid the rare complication of exacerbation of the underlying psychosis. Again, if appropriate, use of antipsychotics that have less of a blocking effect at the D2 receptor may allow lower doses of dopamine agonists to be used in this situation.


Assuntos
Antipsicóticos/efeitos adversos , Agonistas de Dopamina/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Antipsicóticos/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Interações Medicamentosas , Humanos , Hiperprolactinemia/induzido quimicamente , Transtornos Mentais/induzido quimicamente , Prolactina/metabolismo , Prolactinoma/patologia , Receptores de Dopamina D2/efeitos dos fármacos
4.
Sci Rep ; 10(1): 10195, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576969

RESUMO

The velvet belly lanternshark, Etmopterus spinax, uses counterillumination to disappear in the surrounding blue light of its marine environment. This shark displays hormonally controlled bioluminescence in which melatonin (MT) and prolactin (PRL) trigger light emission, while α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) play an inhibitory role. The extraocular encephalopsin (Es-Opn3) was also hypothesized to act as a luminescence regulator. The majority of these compounds (MT, α-MSH, ACTH, opsin) are members of the rapid physiological colour change that regulates the pigment motion within chromatophores in metazoans. Interestingly, the lanternshark photophore comprises a specific iris-like structure (ILS), partially composed of melanophore-like cells, serving as a photophore shutter. Here, we investigated the role of (i) Es-Opn3 and (ii) actors involved in both MT and α-MSH/ACTH pathways on the shark bioluminescence and ILS cell pigment motions. Our results reveal the implication of Es-Opn3, MT, inositol triphosphate (IP3), intracellular calcium, calcium-dependent calmodulin and dynein in the ILS cell pigment aggregation. Conversely, our results highlighted the implication of the α-MSH/ACTH pathway, involving kinesin, in the dispersion of the ILS cell pigment. The lanternshark luminescence then appears to be controlled by the balanced bidirectional motion of ILS cell pigments within the photophore. This suggests a functional link between photoreception and photoemission in the photogenic tissue of lanternsharks and gives precious insights into the bioluminescence control of these organisms.


Assuntos
Movimento/fisiologia , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/fisiologia , Pigmentação/fisiologia , Tubarões/metabolismo , Tubarões/fisiologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Luz , Luminescência , Melatonina/metabolismo , Opsinas/metabolismo , Prolactina/metabolismo , Transdução de Sinais/fisiologia , Pele/metabolismo , Pele/fisiopatologia , alfa-MSH/metabolismo
5.
Enferm. clín. (Ed. impr.) ; 30(supl.5): 202-205, jun. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-196669

RESUMO

Based on preliminary studies, it is known that 80% of working mothers fail to make exclusive breastfeeding, on average babies are given formula milk 2-4 months old and stop breastfeeding at 6-18 months of age. Papaya leaves are one of the galactagogues that contain quercetin which can activate the hormone prolactin and help increase breastmilk. The purpose of this study was to determine the effect of giving papaya leaf juice for nursing mothers who work toward increasing levels of the hormone prolactin and infant weight in Tangerang. The research design used was a pre-experimental model with one group pretest-posttest design. Samples taken as many as 10 mothers who have babies aged 0-6 months who have difficulty in breastfeeding because the amount of breastmilk was a little. The study was conducted in several clinics in Tangerang. The intervention was giving papaya leaf juice for 7 consecutive days. The results obtained from this study are as follows: 90% of mothers aged between 20 and 35 years, 70% of mothers have a history of spontaneous labor and have no complications at the time of delivery, 40% of mother's education is junior high school (SMP), and 70% of mothers are primiparas. The average increase in the amount of prolactin after the intervention was 19.59ng/ml, while the average weight gain of the newborn after the intervention was 165g. Wilcoxon test results for increased levels of the hormone prolactin p-value of 0.047<0.05 and for an increase in body weight of newborns p-value of 0.009<0.05. CONCLUSION: There is an effect of giving papaya leaf juice for nursing mothers who work on increasing levels of the hormone prolactin and infant weight in Tangerang. Papaya leaf juice can be a galactagogue for mothers who experience problems with a small amount of breastmilk


No disponible


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Adulto , Carica/metabolismo , Aleitamento Materno/métodos , Hormônio Liberador de Prolactina , Leite Humano/metabolismo , Mães , Comportamento Alimentar , Glândulas Mamárias Humanas/metabolismo , Glândulas Mamárias Humanas/fisiologia , Prolactina/metabolismo
6.
Nat Commun ; 11(1): 2506, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427851

RESUMO

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics.


Assuntos
Fosfoproteínas/genética , Prolactinoma/genética , Fatores de Processamento de RNA/genética , Adulto , Feminino , Humanos , Masculino , Mutação , Fosfoproteínas/metabolismo , Intervalo Livre de Progressão , Prolactina/genética , Prolactina/metabolismo , Prolactinoma/metabolismo , Prolactinoma/mortalidade , Fatores de Processamento de RNA/metabolismo , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Fator de Transcrição Pit-1/genética , Fator de Transcrição Pit-1/metabolismo , Adulto Jovem
8.
Sci Rep ; 10(1): 1674, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015405

RESUMO

Growth hormone receptor (GHR) and prolactin receptor (PRLR) in jawed vertebrates were thought to arise after the divergence of gnathostomes from a basal vertebrate. In this study we have identified two genes encoding putative GHR and PRLR in sea lamprey (Petromyzon marinus) and Arctic lamprey (Lethenteron camtschaticum), extant members of one of the oldest vertebrate groups, agnathans. Phylogenetic analysis revealed that lamprey GHR and PRLR cluster at the base of gnathostome GHR and PRLR clades, respectively. This indicates that distinct GHR and PRLR arose prior to the emergence of the lamprey branch of agnathans. In the sea lamprey, GHR and PRLR displayed a differential but overlapping pattern of expression; GHR had high expression in liver and heart tissues, whereas PRLR was expressed highly in the brain and moderately in osmoregulatory tissues. Branchial PRLR mRNA levels were significantly elevated by stage 5 of metamorphosis and remained elevated through stage 7, whereas levels of GHR mRNA were only elevated in the final stage (7). Branchial expression of GHR increased following seawater (SW) exposure of juveniles, but expression of PRLR was not significantly altered. The results indicate that GHR and PRLR may both participate in metamorphosis and that GHR may mediate SW acclimation.


Assuntos
Hormônio do Crescimento/metabolismo , Petromyzon/metabolismo , Prolactina/metabolismo , Animais , Metamorfose Biológica/fisiologia , Filogenia , RNA Mensageiro/metabolismo , Receptores da Prolactina/metabolismo , Receptores da Somatotropina/metabolismo , Água do Mar , Vertebrados/metabolismo
9.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R760-R771, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32048872

RESUMO

Morphological and behavioral evidence suggests that vasoinhibin is present in the central nervous system (CNS), triggering neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin reduces neuronal survival and differentiation of primary sensory neurons of the peripheral nervous system. To address the functional role played by vasoinhibin at the CNS, and to better understand the underlying mechanisms involved in its actions, we treated primary cultured hippocampal neurons obtained from embryonic day 16 (E16) mice with a human recombinant vasoinhibin. We examined the resulting cellular changes, focusing on neuronal cell death, and explored the local generation of vasoinhibin within the hippocampus. Our results show that vasoinhibin significantly reduced neuronal cell density and increased immunoreactive activated caspase-3 and TUNEL-positive staining at 72, 16, and 24 h, respectively. Furthermore, vasoinhibin increased the expression of proapoptotic genes BAX, BAD, BIM, and PUMA and decreased that of the antiapoptotic gene BCL-2 at 24 h, as assessed by quantitative real-time reverse transcription-polymerase chain reaction. Vasoinhibin effects were blocked by coincubation with a vasoinhibin antibody or with prolactin. Immunoreactive bands consistent with vasoinhibin were observed in hippocampal extracts by Western blot analysis, and a prolactin standard was cleaved to vasoinhibin by a hippocampal lysate in a heat- and cathepsin D inhibitor pepstatin A-dependent fashion. Taken together, these data support the notion that vasoinhibin is locally produced by cathepsin D within the embryonic mouse hippocampus, a brain region that plays a critical role in emotional regulation, resulting in decreased neuronal cell viability via the activation of the intrinsic apoptosis pathway.


Assuntos
Apoptose/fisiologia , Hipocampo/metabolismo , Neurônios/fisiologia , Animais , Proteínas de Ciclo Celular/metabolismo , Regulação para Baixo , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/embriologia , Camundongos , Prolactina/metabolismo , Regulação para Cima
10.
BMC Complement Med Ther ; 20(1): 42, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046715

RESUMO

BACKGROUND: Qilin pills (QLPs), a classic Traditional Chinese Medicine (TCM) formula for treating male infertility, effectively improve semen quality in clinical trials. This study was designed to evaluate the effects of QLPs on spermatogenesis, reproductive hormones, oxidative stress, and the testis-specific serinekinase-2 (TSSK2) gene in a rat model of oligoasthenospermia. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups. The rat model with oligoasthenospermia was generated by intragastric administration of tripterygium glycosides (TGs) once daily for 4 weeks. Then, two treatment groups were given different doses (1.62 g/kg and 3.24 g/kg) of QLPs once daily for 60 days. Sperm parameters, testicular histology and reproductive hormone measurements, oxidative stress tests, and TSSK2 expression tests were carried out. RESULTS: QLPs effectively improved semen parameters and testicular histology; restored the levels of FSH, LH, PRL, fT, and SHBG; reduced the levels of oxidative stress products (ROS and MDA); increased testicular SOD activity; and restored the expression of spermatogenesis-related gene TSSK2. CONCLUSION: QLPs have a therapeutic effect on a rat model of oligoasthenospermia, and this effect is manifested as improvement of semen quality and testis histology, gonadal axis stability, decreased oxidative stress, and the regulation of testis-specific spermatogenesis-related gene TSSK2.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hormônios/metabolismo , Oligospermia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Espermatogênese/efeitos dos fármacos , Animais , China , Modelos Animais de Doenças , Gonadotropinas Hipofisárias/metabolismo , Masculino , Medicina Tradicional Chinesa , Prolactina/metabolismo , Ratos , Ratos Sprague-Dawley , Globulina de Ligação a Hormônio Sexual/metabolismo , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/metabolismo
11.
J Med Case Rep ; 14(1): 34, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32079542

RESUMO

BACKGROUND: Lipodystrophies are a group of diseases which are characterized by abnormal adipose tissue deposition and are frequently associated with metabolic changes. Congenital generalized lipodystrophy is an autosomal recessive syndrome, with a prevalence < 1:10 million. Acromegaly is a rare disease, secondary to the chronic hypersecretion of growth hormone and insulin-like growth factor-1, with characteristic metabolic and somatic effects. "Acromegaloidism" is a term used for patients who manifest clinical features of acromegaly, but do not present a demonstrable hormone growth hypersecretion. The extreme shortage of subcutaneous adipose tissues and muscle hypertrophy confer an acromegaloid-like appearance in these patients. CASE PRESENTATION: We describe a case of a patient with the rare combination of Berardinelli-Seip congenital lipodystrophy and acromegaly; our patient is a 63-year-old white man, who was referred to an endocrinology consultation for suspected lipodystrophy. He had lipoatrophy of upper and lower limbs, trunk, and buttocks, with muscular prominence, acromegaloid facial appearance, large extremities, and soft tissue tumescence. In addition, he had dyslipidemia and prediabetes. His fat mass ratio (% trunk fat mass/% lower limbs fat mass) was 1.02 by densitometry and he also had hepatomegaly, with mild steatosis (from an abdominal ultrasound), and left ventricular hypertrophy (from an electrocardiogram). His first oral glucose tolerance test had growth hormone nadir of 0.92 ng/mL, and the second test, 10 months afterwards, registered growth hormone nadir of 0.64 ng/mL (growth hormone nadir < 0.3 ng/mL excludes acromegaly). Pituitary magnetic resonance imaging identified an area of hypocaptation of contrast product in relation to a pituitary adenoma and he was subsequently submitted to transsphenoidal surgical resection of the mass. A pathological evaluation showed pituitary adenoma with extensive expression of growth hormone and adrenocorticotropic hormone, as well as a rare expression of follicle-stimulating hormone and prolactin. A genetic study revealed an exon 3/exon 4 deletion of the AGPAT2 gene in homozygosity. CONCLUSIONS: Congenital generalized lipodystrophy is a rare disease which occurs with acromegaloid features. As far as we know, we have described the first case of genetic lipodystrophy associated with true acromegaly. Although this is a rare association, the presence of congenital generalized lipodystrophy should not exclude the possibility of simultaneous acromegaly.


Assuntos
Acromegalia/complicações , Adenoma/patologia , Hormônio do Crescimento Humano/metabolismo , Lipodistrofia Generalizada Congênita/complicações , Neoplasias Hipofisárias/patologia , Aciltransferases/genética , Hormônio Adrenocorticotrópico/metabolismo , Dislipidemias/complicações , Éxons , Hormônio Foliculoestimulante/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Prolactina/metabolismo
12.
J Biol Chem ; 295(8): 2438-2448, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31953323

RESUMO

How and when disulfide bonds form in proteins relative to the stage of their folding is a fundamental question in cell biology. Two models describe this relationship: the folded precursor model, in which a nascent structure forms before disulfides do, and the quasi-stochastic model, where disulfides form prior to folding. Here we investigated oxidative folding of three structurally diverse substrates, ß2-microglobulin, prolactin, and the disintegrin domain of ADAM metallopeptidase domain 10 (ADAM10), to understand how these mechanisms apply in a cellular context. We used a eukaryotic cell-free translation system in which we could identify disulfide isomers in stalled translation intermediates to characterize the timing of disulfide formation relative to translocation into the endoplasmic reticulum and the presence of non-native disulfides. Our results indicate that in a domain lacking secondary structure, disulfides form before conformational folding through a process prone to nonnative disulfide formation, whereas in proteins with defined secondary structure, native disulfide formation occurs after partial folding. These findings reveal that the nascent protein structure promotes correct disulfide formation during cotranslational folding.


Assuntos
Proteína ADAM10/química , Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Dissulfetos/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Prolactina/química , Prolactina/metabolismo , Dobramento de Proteína , Microglobulina beta-2/química , Microglobulina beta-2/metabolismo , Animais , Bovinos , Cisteína/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Modelos Moleculares , Domínios Proteicos , Estrutura Secundária de Proteína , Ribossomos/metabolismo , Processos Estocásticos , Fatores de Tempo
13.
Fish Physiol Biochem ; 46(2): 501-517, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31970604

RESUMO

The pituitary hormone prolactin (PRL) regulates salt and water homeostasis by altering ion retention and water uptake through peripheral osmoregulatory organs. To understand the role of PRL and its receptor (PRLR) in hypoosmoregulation of turbot (Scophthalmus maximus), we characterized the PRL and PRLR gene and analyzed the tissue distribution of the two genes and their gene transcriptional patterns in the main expressed tissues under long-term and short-term low salt stress. The PRL cDNA is 1486 bp in length, incorporating an ORF of 636 bp with a putative primary structure of 211 residues. And the PRLR cDNA is 2849 bp in length, incorporating an ORF of 1944 bp with a putative primary structure of 647 residues. The deduced amino acid sequences of these two genes shared highly conserved structures with those from other teleosts. Quantitative real-time PCR results showed that PRL transcripts were strongly expressed in the pituitary and very weakly in brain, but were hardly expressed in other tissues. PRLR transcripts were most abundant in the kidney, to a lesser extent in the gill, intestine, brain, and spleen, and at low levels in the pituitary and other tissues examined. The expression of PRL in the pituitary increased after short-term or long-term low salt stress, and the highest expression level appeared 12 h after stress (P < 0.05). And there is no significant difference between both low salt group (5 ppt and 10 ppt) at each sampling point. The variation of PRLR expression in gill under short-term low salt stress is similar to that of PRL gene in pituitary, with highest value in 12 h (P < 0.05). However, the expression under long-term low salt stress was significantly higher than control group even than 12 h group under 5 ppt (P < 0.05). The expression of PRLR in the kidney increased first and then decreased after low salt stress, and the highest value also appeared in 12 h after stress and there was no significant difference between the salinity groups. After long-term low salt stress, the expression level also increased significantly (P < 0.05), but it was flat with 24 h, which was lower than 12 h. The variation of PRLR expression in the intestine was basically consistent with that in the kidney. The difference was that the expression level of 24 h after stress in the 5 ppt group was significantly higher than that of the 10 ppt group (P < 0.05). After a comprehensive analysis of the expression levels of the two genes, it can be found that the expression level increased and peaked at 12 h after short-term low salt stress, indicating that this time point is the key point for the regulation of turbot in response to low salt stress. This also provides very important information for studying the osmotic regulation of turbot. In addition, our results also showed that the expression of PRLR was stable in the kidney and intestine after long-term low salt stress, while the expression in the gill was much higher than short-term stress. It suggested that PRL and its receptors mainly exert osmotic regulation function in the gill under long-term low salt stress. At the same time, such a result also brings a hint for the low salt selection of turbot, focusing on the regulation of ion transport in the gill.


Assuntos
Linguados/fisiologia , Prolactina/metabolismo , Receptores da Prolactina/metabolismo , Estresse Salino/fisiologia , Animais , DNA Complementar , Brânquias , Hipófise , Hormônios Hipofisários , Salinidade
14.
Biochem Biophys Res Commun ; 524(2): 288-294, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31987497

RESUMO

Successful induction of milk protein synthesis relies on prolactin/STAT5. In mice, both laminin and ß1 integrin were necessary for STAT5 activity induced by prolactin treatment, resulting in transcriptional activation of ß-casein. However, the mechanism by which ß1 integrin increases the bovine milk protein synthesis is not well known. In order to display the crosstalk between integrin signaling and lactogenic signaling, we investigated the mechanism by which laminin mediated lactogenic effects via interaction with ß1 integrin on bovine mammary epithelial cells (BMECs). Therefore, localization of ß1 integrin was examined by immunofluorescence. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blotting. The results showed that ß1 integrin were detected in basal mammary cells and basal membrane surface of adherent BMECs. However, basal distribution of ß1 integrin was not sufficient to increase ß-casein synthesis in the absence of integrin activation by laminin. A lactogenic hormone cocktail of insulin, hydrocortisone, and prolactin stimulated overall lactogenic effects, including upregulated expression of ß1 integrin, activation of prolactin/STAT5 signaling, and consequent increase of ß-casein synthesis. In response to a 24 h prolactin treatment, the abundance of STAT5, ß1 integrin, and ß-casein in BMECs with laminin was higher compared to that with a control substratum. Meanwhile, laminin-dependent lactogenic effects were inhibited by blocking ß1 integrin function, resulting in attenuated STAT5 activity and decreased ß-casein synthesis. These results indicated that ß1 integrin was a key mediator of the laminin-dependent prolactin/STAT5 signaling, which regulated the sustained STAT5 activity necessary for ß-casein expression in BMECs.


Assuntos
Bovinos/metabolismo , Integrina beta1/metabolismo , Laminina/metabolismo , Proteínas do Leite/metabolismo , Prolactina/metabolismo , Fator de Transcrição STAT5/metabolismo , Animais , Células Epiteliais/metabolismo , Feminino , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Biossíntese de Proteínas , Transdução de Sinais
15.
J Biol Chem ; 295(8): 2248-2258, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31937587

RESUMO

The regulation mechanisms involved in matrix metalloproteinase (MMP) expression and the motility of human endometrial and decidual stromal cells (ESCs and DSCs, respectively) during decidualization remain unclear. DSCs show significant increased cell motility and expression of FOS-like 1 (FOSL1) and MMP1, MMP2, and MMP9 compared with ESCs, whereas lack of decidualization inducers leads to a rapid decrease in FOSL1 and MMP1 and MMP9 expression in DSCs in vitro Therefore, we hypothesized that a link exists between decidualization inducers and FOSL1 in up-regulation of motility during decidualization. Based on the response of ESCs/DSCs to different decidualization systems in vitro, we found that progesterone (P4) alone had no significant effect and that 17ß-estradiol (E2) significantly increased cell motility and FOSL1 and MMP1 and MMP9 expression at the mRNA and protein levels, whereas 8-bromo-cAMP significantly decreased cell motility and FOSL1 and MMP9 expression in the presence of P4. In addition, we showed that E2 triggered phosphorylation of estrogen receptor 1 (ESR1), which could directly bind to the promoter of FOSL1 in ESCs/DSCs. Additionally, we also revealed silencing of ESR1 expression by siRNA abrogated E2-induced FOSL1 expression at the transcript and protein levels. Moreover, silencing of FOSL1 expression by siRNA was able to block E2-induced MMP1 and MMP9 expression and cell motility in ESCs/DSCs. Taken together, our data suggest that, in addition to its enhancement of secretory function, the change in MMP expression and cell motility is another component of the decidualization of ESCs/DSCs, including estrogen-dependent MMP1 and MMP9 expression mediated by E2-ESR1-FOSL1 signaling.


Assuntos
Movimento Celular , Decídua/citologia , Endométrio/citologia , Estrogênios/farmacologia , Metaloproteinases da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Adulto , Movimento Celular/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Pessoa de Meia-Idade , Prolactina/metabolismo , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Células Estromais/enzimologia , Adulto Jovem
16.
Basic Clin Pharmacol Toxicol ; 126(3): 236-246, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31520576

RESUMO

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty-one healthy volunteers receiving a 10-mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro-aripiprazole plasma concentrations were measured by HPLC-MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0-12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.


Assuntos
Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Farmacogenética , Prolactina/metabolismo , Adolescente , Adulto , Antipsicóticos/farmacocinética , Aripiprazol/farmacocinética , Ritmo Circadiano , Estudos Cross-Over , Citocromo P-450 CYP2D6/genética , Feminino , Humanos , Ibuprofeno/farmacologia , Masculino , Piperazinas/farmacocinética , Quinolonas/farmacocinética , Receptor 5-HT2C de Serotonina/genética , Receptores de Dopamina D3/genética , Fatores Sexuais , Adulto Jovem
17.
Mol Cell Endocrinol ; 499: 110605, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580897

RESUMO

The contribution of the pleiotropic hormone Prolactin (PRL) to several physiological and pathological processes is still unknown. To clarify the role of PRL in these processes during the last decade, different human PRL antagonists have been produced to either partially or fully block the wild type hormone activity. In this work, we have cloned these wild type and antagonist sequences in lentivectors (LV) to express them as recombinant self-processing polypeptides by employing a P2A sequence (hPRL-P2A-GFP). We show that these LVs can efficiently transduce and express the hPRL proteins in different cell types and that the P2A sequence does not affect their activities. Additionally, we have tested their activities in paracrine and autocrine cell culture experiments. Our results demonstrate that these recombinant hPRL-P2A proteins are bioactive in both paracrine and autocrine modes, highlighting the potential usefulness of these hPRL-containing LVs for determining the contribution of hPRL to different biological processes.


Assuntos
Lentivirus/genética , Prolactina/genética , Engenharia de Proteínas/métodos , Proteínas Recombinantes/metabolismo , Animais , Comunicação Autócrina , Técnicas de Cultura de Células , Linhagem Celular , Vetores Genéticos , Células HEK293 , Humanos , Comunicação Parácrina , Prolactina/metabolismo , Ratos
18.
Animal ; 14(2): 330-338, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31337460

RESUMO

Calcium homeostasis is crucial for the normal function of the organism. Parathyroid hormone, calcitriol and calcitonin play critical roles in the homeostatic regulation of calcium. Serotonin and prolactin have also been shown to be involved in the regulation of calcium homeostasis. In modern dairy cows, the endocrine pathways controlling calcium homeostasis during non-lactating and non-pregnant physiological states are unable to fully support the increased demand of calcium required for milk synthesis at the onset of lactation. This review describes different endocrine systems associated with the regulation of calcium homeostasis in mammalian species around parturition with special focus on dairy cows. Additionally, classic and novel strategies to reduce the incidence of hypocalcemia in parturient dairy cows are discussed.


Assuntos
Cálcio na Dieta/metabolismo , Doenças dos Bovinos/metabolismo , Sistema Endócrino/metabolismo , Hipocalcemia/veterinária , Leite/metabolismo , Animais , Bovinos , Feminino , Homeostase , Hipocalcemia/metabolismo , Lactação , Glândulas Mamárias Animais/metabolismo , Hormônio Paratireóideo/metabolismo , Parto , Gravidez , Prolactina/metabolismo , Serotonina/metabolismo
19.
Biochem Biophys Res Commun ; 521(2): 521-526, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31677791

RESUMO

Neuromedin U (NMU) has a precursor that contains one additional peptide consisting of 33 or 36 amino acid residues. Recently, we identified this second peptide from rat brain and designated it neuromedin U precursor-related peptide (NURP), showing it to stimulate prolactin release from the pituitary when injected via the intracerebroventricular (icv) route. Here, we examined whether NMU, like NURP, also stimulates prolactin release. Unlike NURP, icv injection of NMU significantly decreased the secretion of prolactin from the pituitary. This suppression of prolactin release by NMU was observed in hyper-prolactin states such as lactation, stress, pseudopregnancy, domperidone (dopamine antagonist) administration, and icv injection of NURP. Immunohistochemical analysis revealed that icv injection of NMU induced cFos expression in dopaminergic neurons of the arcuate nucleus, but not the substantia nigra. Mice with double knockout of NMU and neuromedin S (NMS), the latter also binding to NMU receptors, showed a significant increase of the plasma prolactin level after domperidone treatment relative to wild-type mice. These results suggest that NMU and NURP may play important reciprocal roles in physiological prolactin secretion.


Assuntos
Núcleo Arqueado do Hipotálamo/citologia , Neurônios Dopaminérgicos/metabolismo , Neuropeptídeos/fisiologia , Prolactina/metabolismo , Animais , Camundongos , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Receptores de Neurotransmissores
20.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665485

RESUMO

CONTEXT: The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. OBJECTIVE: To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. METHODS: Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. RESULTS: A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.


Assuntos
Procedimentos Clínicos/normas , Agonistas de Dopamina/uso terapêutico , Hipofisectomia/métodos , Microcirurgia/métodos , Neoplasias Hipofisárias/terapia , Prolactinoma/terapia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/normas , Feminino , Humanos , Hipofisectomia/efeitos adversos , Hipofisectomia/normas , Microcirurgia/efeitos adversos , Microcirurgia/normas , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Guias de Prática Clínica como Assunto , Prolactina/metabolismo , Prolactinoma/patologia , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento
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