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1.
Ecotoxicol Environ Saf ; 188: 109912, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706240

RESUMO

Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.


Assuntos
Androstenos/toxicidade , Carpas/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Norpregnenos/toxicidade , Diferenciação Sexual/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Hepatopâncreas/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Diferenciação Sexual/genética
2.
Eur J Endocrinol ; 181(4): C13-C15, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505455

RESUMO

A study has examined the rates of adrenal crises in patients treated with pituitary or adrenal surgery. Rates were substantial (approximately 9 per 100 patient years), perhaps representing suppression of corticotrope ACTH secretion and deprivation of normal corticotrope number postoperatively. Hormone withdrawal syndrome may have contributed to the rates of apparent adrenal crises given the definition used. Higher rates were seen in patients given relatively high dose glucocorticoids postoperatively in one of the two centres where patients were treated - perhaps some of the patients in the high dose centre had longer periods of corticotrope suppression from exogenous glucocorticoids, increasing the risk period for adrenal crises. The question of optimal glucocorticoid dose and weaning rate after cure of Cushing's syndrome remains a balance between weaning at a rate sufficiently rapid to allow resumption of normal corticotrope function thereby preventing adrenal crises and providing sufficient glucocorticoid support to avoid hormone withdrawal syndrome or even precipitating an adrenal crisis, in the vulnerable 4-6 month period after successful surgery. There is likely to be considerable inter-individual variability in optimum glucocorticoid dose and weaning rate so that close clinical and biochemical monitoring is currently a practical approach.


Assuntos
Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/terapia , Glândulas Suprarrenais/efeitos dos fármacos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Estudos Multicêntricos como Assunto/métodos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Resultado do Tratamento
3.
Aquat Toxicol ; 214: 105240, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319295

RESUMO

Fish has a strong resistance to microcystins (MCs), cyclic heptapeptide cyanotoxins, known as endocrine disrupting chemicals (EDCs) which are released during cyanobacterial blooms and many laboratory and field studies have found the hepatic recovery of fish from the MCs exposure. The aim of the present study was to investigate the recovery mechanisms of reproductive function of adult zebrafish (Danio rerio) from microcystin-LR (MC-LR) exposure. Therefore, adult female zebrafish were exposed to 0, 1 or 50 µg/L of MC-LR for 21days and transferred to MC free water for another 21 days to investigate the recovery. After MC-LR exposure, marked histological lesions in the gonads, decreased the percentage of mature oocytes, decreased number of spawned eggs, decreased fertilization and hatching rates were observed. MC-LR exposure increased the concentration of 17ß-estradiol (E2), testosterone (T) and vitellogenin (VTG) in female zebrafish. Some gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis significantly changed. The protein levels of 17ßhsd and cyp19a remarkably increased in the MC-LR exposure groups. However, our laboratory observation also indicates that zebrafish transferred from microcystin exposure to toxin-free water and reared for 21 days exhibited a nearly complete recovery of reproductive functions, including histological structure, increased the percentage of matured oocytes and spawned eggs, stable hormone levels, well-balanced transcriptional and translational levels. These results indicate that after MC-LR exposure, the reproductive impairments in zebrafish are also reversible likewise hepatic recovery seen by different studies in fish. Future studies should be conducted to explore a better understanding of the recovery mechanisms of fish from microcystins exposure.


Assuntos
Exposição Ambiental , Microcistinas/toxicidade , Reprodução/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Disruptores Endócrinos/toxicidade , Feminino , Hormônios/sangue , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ovário/citologia , Ovário/efeitos dos fármacos , Ovário/fisiologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/sangue , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
4.
BMC Genomics ; 20(1): 597, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331264

RESUMO

BACKGROUND: The impossibility of closing the life cycle of the European eel (Anguilla anguilla) in captivity troubles the future of this critically endangered species. In addition, the European eel is a highly valued and demanded resource, thus the successful closing of its life cycle would have a substantial economic and ecological impact. With the aim of obtaining the highest gamete quality, the study of the effects of environmental factors, such as temperature, on reproductive performance may prove valuable. This is especially true for the exposure to cold water, which has been reported to improve sexual development in multiple other Actinopterygii species. RESULTS: European eel males treated with cold seawater (10 °C, T10) for 2 weeks showed an increase in the proliferation and differentiation of spermatogonial cells until the differentiated spermatogonial type A cell stage, and elevated testosterone and 11-ketotestosterone plasma levels. Transcriptomes from the tissues of the brain-pituitary-gonad (BPG) axis of T10 samples revealed a differential gene expression profile compared to the other experimental groups, with clustering in a principal component analysis and in heat maps of all differentially expressed genes. Furthermore, a functional analysis of differentially expressed genes revealed enriched gene ontology terms involved in the regulation of circadian rhythm, histone modification, meiotic nuclear division, and others. CONCLUSIONS: Cold seawater treatment had a clear effect on the activity of the BPG-axis of European eel males. In particular, our cold seawater treatment induces the synchronization and increased proliferation and differentiation of specific spermatogonial cells. In the transcriptomic results, genes related to thermoception were observed. This thermoception may have caused the observed effects through epigenetic mechanisms, since all analysed tissues further revealed differentially expressed genes involved in histone modification. The presented results support our hypothesis that a low temperature seawater treatment induces an early sexual developmental stage in European eels. This hypothesis is logical given that the average temperature experienced by eels in the early stages of their oceanic reproductive migration is highly similar to that of this cold seawater treatment. Further studies are needed to test whether a cold seawater treatment can improve the response of European eels to artificial hormonal treatment, as the results suggest.


Assuntos
Anguilla/crescimento & desenvolvimento , Encéfalo/efeitos dos fármacos , Temperatura Baixa , Hipófise/efeitos dos fármacos , Água do Mar/química , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Anguilla/genética , Anguilla/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Masculino , Anotação de Sequência Molecular , Hipófise/metabolismo , Hipófise/fisiologia , Testículo/metabolismo , Testículo/fisiologia , Fatores de Tempo , Transcriptoma/efeitos dos fármacos
5.
Life Sci ; 231: 116578, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31211996

RESUMO

AIMS: The aim of the present study is to shed light on the modulating action of selenium on two of the most crucial cellular pathways; apoptosis and autophagy and the possible interplay between them in determining the pituitary fate in the context of mercury intoxication through demonstration of the molecular, histopathological, immunohistochemical, and ultrastructural features of selenium mercury-treated adenohypophysis. METHODS: Thirty adult Sprague Dawley male albino rats were assigned into control group, mercury-treated group and mercury­selenium concomitantly-treated group. The adenohypophysis was subjected to structural, molecular and protein expression assessment of autophagy and apoptotic markers and western blotted analysis of Beclin 1 as a key cross-regulator of autophagy and apoptosis. KEY FINDINGS: Selenium treatment ameliorated the mercury-induced apoptosis detected by improvement in PCR and immunohistochemical expression of the apoptotic markers Bax, Bcl-2 and Caspase-3. Selenium also improved mercury-induced autophagic dysfunction with statistically significant improvement in western blotted levels of the autophagy markers LC3I, LC3II and Beclin1. The histopathological and ultrastructural studies strongly confirmed those findings. SIGNIFICANCE: The crosstalk between the apoptotic Bcl-2 family of proteins and the autophagic Beclin-1LC3 pathway in the context of mercury intoxication paves the way for developing novel effective treatment strategies for several mercury-induced pituitary diseases.


Assuntos
Intoxicação por Mercúrio/prevenção & controle , Mercúrio/toxicidade , Hipófise/efeitos dos fármacos , Selênio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Masculino , Intoxicação por Mercúrio/metabolismo , Intoxicação por Mercúrio/patologia , Hipófise/metabolismo , Hipófise/patologia , Adeno-Hipófise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
6.
Med Sci Monit ; 25: 4377-4383, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31187785

RESUMO

BACKGROUND Patients with endometriosis (EMs) are routinely advised to take GnRH-a for 3-6 months to improve the internal reproductive environment, but this may not be necessary. MATERIAL AND METHODS This retrospective study examined the effects of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with shortened (n=311) or conventional (n=213) long-term pituitary downregulation in EMs patients between January 2013 and July 2017. RESULTS The 2 groups showed no significant differences in gonadotropin (Gn) dose, number of oocytes retrieved, or miscarriage rate. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on the initiation day and the LH level on human chorionic gonadotropin (hCG) day (1.22±1.39 vs. 0.74±0.55 P=0.0026) were higher in the study group than in the control group. The cumulative live birth rates in the second cycle were 69.13% in the study group (95% confidence interval (CI), 64-74.27%) vs. 68.54% in the control group (95% CI, 62.31-74.78%, P=0.88, respectively). CONCLUSIONS This study showed that the shortened regimen and the ultralong regimen did not produce different pregnancy outcomes after ART, and the single-application, long-term GnRH-a protocol may serve as a cost-effective and safe treatment protocol for EMs patients.


Assuntos
Fertilização In Vitro/métodos , Hormônio Liberador de Gonadotropina/farmacologia , Injeções de Esperma Intracitoplásmicas/métodos , Aborto Espontâneo , Adulto , Gonadotropina Coriônica/farmacologia , Regulação para Baixo , Transferência Embrionária , Endometriose/complicações , Feminino , Humanos , Recuperação de Oócitos/métodos , Oócitos/efeitos dos fármacos , Indução da Ovulação , Hipófise/efeitos dos fármacos , Hipófise/patologia , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Resultado do Tratamento
7.
Gen Comp Endocrinol ; 282: 113209, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226256

RESUMO

The highly conserved brain-pituitary-gonadal (BPG) axis controls reproduction in all vertebrates, so analyzing the regulation of this signaling cascade is important for understanding reproductive competence. The protein kinase mechanistic target of rapamycin (mTOR) functions as a conserved regulator of cellular growth and metabolism in all eukaryotes, and also regulates the reproductive axis in mammals. However, whether mTOR might also regulate the BPG axis in non-mammalian vertebrates remains unexplored. We used complementary experimental approaches in an African cichlid fish, Astatotilapia burtoni, to demonstrate that mTOR is involved in regulation of the brain, pituitary, and testes when males rise in rank to social dominance. mTOR or downstream components of its signaling pathway (p-p70S6K) were detected in gonadotropin-releasing hormone (GnRH1) neurons, the pituitary, and testes. Transcript levels of mtor in the pituitary and testes also varied when reproductively-suppressed subordinate males rose in social rank to become dominant reproductively-active males, a transition similar to puberty in mammals. Intracerebroventricular injection of the mTORC1 inhibitor, rapamycin, revealed a role for mTOR in the socially-induced hypertrophy of GnRH1 neurons. Rapamycin treatment also had effects at the pituitary and testes, suggesting involvement of the mTORC1 complex at multiple levels of the reproductive axis. Thus, we show that mTOR regulation of BPG function is conserved to fishes, likely playing important roles in regulating reproduction and fertility across all male vertebrates.


Assuntos
Ciclídeos/fisiologia , Reprodução/fisiologia , Predomínio Social , Serina-Treonina Quinases TOR/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclídeos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/genética , Testículo/efeitos dos fármacos , Testículo/metabolismo
8.
J Coll Physicians Surg Pak ; 29(7): 600-603, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31253206

RESUMO

OBJECTIVE: To determine the effects of prenatal administration of ethanol on cell count in pars distalis of pituitary gland in the rat pups. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Anatomy, College of Physicians and Surgeons Pakistan, Regional Centre, Islamabad, Pakistan, from April 2014 to April 2015. METHODOLOGY: Sixteen female rats (Sprague Dawley) were selected by random sampling method. Rats were mated and divided into control group A and experimental group B. From gestational day 10 to 18, mother rats received intraperitoneal injection of ethanol (Group B) and normal saline (Group A). Mother rats were allowed to complete their gestation and deliver spontaneously. When pups were born, only male pups were selected for the study. They were reared till day five. At 5ᵗʰ; day, pituitary glands were taken out and histological study was done in PAS-OG stain. Cell count was made in unit area (10,000 µ2) of pars distalis of pituitary gland. Student t-test was applied for analysing the data of cell counts in unit area. RESULTS: Mean acidophil count was reduced in experimental group (70.19 ± 11.4) as compared to control group (92.65 ± 8.52, p<0.001). Mean basophil count was reduced in experimental group (27.05 ± 3.9) in comparison to control group (34.03 ± 7.9, p<0.001). Mean chromophobe count was increased (131.95 ± 10.7) in experimental group against the control group (104.62 ± 7.62, p < 0.001). CONCLUSION: Pups exposed to ethanol during gestation, showed significant reduction in acidophil and basophil count while increase in chromophobe cell count in pars distalis of pituitary gland.


Assuntos
Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Hipófise/efeitos dos fármacos , Hipófise/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Animais Recém-Nascidos , Contagem de Células , Modelos Animais de Doenças , Feminino , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley
9.
Aquat Toxicol ; 212: 70-76, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077968

RESUMO

Medroxyprogesterone acetate (MPA) is a widely used synthetic progestin and it has been frequently detected in aquatic environments. However, its effects on aquatic organisms remain largely unknown. Here we investigated the chronic effects of MPA on sex differentiation and gonad development in zebrafish. Zebrafish larvae at 20 days post fertilization (dpf) were exposed to 4.32, 42.0, and 424 ng L-1 of MPA until they reached 140 dpf. The results showed that chronic exposure to 42.0 ng L-1 of MPA caused 60% proportion of males as well as significant up-regulation of dmrt1 (˜1.79 fold) and hsd17b3 (˜1.92 fold). Histological analysis showed MPA significantly increased the frequency of immature spermatocytes accompanied with the increased transcription of dmrt1 (˜2.06 fold) and ar (˜1.73 fold) in the testes. Meanwhile, MPA exposure significantly increased the transcription of lhb at all exposure concentrations in the males. In contrast, it significantly suppressed the transcription of lhb (˜-8.06-fold) and fshb (˜-6.35-fold) at 42.0 ng L-1 in the females. Collectively our results demonstrated that MPA had androgenic activity, and could affect sex differentiation and spermatogenesis in zebrafish at environmentally relevant concentrations. The findings from this study suggest that MPA in the aquatic environment may pose potential androgenic risks to fish populations.


Assuntos
Acetato de Medroxiprogesterona/farmacologia , Diferenciação Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Hormônios/sangue , Masculino , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Razão de Masculinidade , Transcrição Genética/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/sangue , Peixe-Zebra/crescimento & desenvolvimento
10.
Drugs ; 79(9): 935-956, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31098899

RESUMO

Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, and long-term medical treatment is used to decrease cortisol levels and risk of metabolic comorbidities. Medical treatment is also often required while waiting for radiation effects to take place. In some cases, severe or life-threatening hypercortisolism must be urgently and medically treated, via intravenous medications or with combination therapy, before patients can undergo surgery. In the last decade, medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer side effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing's disease, and glucocorticoid receptor antagonists that block cortisol's action. Understanding the pathophysiology of Cushing's syndrome has also led to the identification of potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess, and/or decrease tumor cell proliferation, and induce senescence or apoptosis. We provide here a review of current and near-future medical options to treat Cushing's syndrome, and discuss updates on clinical trials and the efficacy and safety of novel or in-development drugs, as well as future potential targets.


Assuntos
Hormônio Adrenocorticotrópico/antagonistas & inibidores , Síndrome de Cushing/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Hidrocortisona/biossíntese , Receptores de Glucocorticoides/antagonistas & inibidores , Ensaios Clínicos como Assunto , Síndrome de Cushing/metabolismo , Quimioterapia Combinada , Endocrinologia/métodos , Endocrinologia/tendências , Inibidores Enzimáticos/farmacologia , Humanos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Receptores de Glucocorticoides/metabolismo , Resultado do Tratamento
11.
Aquat Toxicol ; 212: 98-109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082703

RESUMO

The present study assesses the response of vasotocinergic system in the gilthead sea bream (Sparus aurata) after administering two doses of the polychlorinated biphenyl Aroclor 1254 (15 or 50 µg g-1 fresh body mass). Seven days post-administration, eight fish of each experimental group were sampled, and the remaining animals were challenged with a hyperosmotic stress by being transferred from seawater (36 ppt) to high salinity water (55 ppt) and being sampled 3 days post-transfer. Aroclor 1254 affected gene expression of avt, together with Avt concentrations in pituitary and plasma, inhibiting the stimulation observed in vasotocinergic system after hyperosmotic challenge. This was noted by the accumulation of Avt at hypophyseal level as well as by its undetectable values in plasma. Hyperosmotic transfer significantly changed branchial avtrv1a, avtrv2, atp1a and cftr mRNA expression levels in control fish, while in Aroclor 1254-treated fish they remained mostly unchanged. This desensitization also occurred for avtrs in hypothalamus, caudal kidney and liver. In addition, an enhancement in plasma cortisol concentration, together with the orchestration of several players of the Hypothalamic-Pituitary-Interrenal axis (crh, crhbp, trh, star), was also observed mostly at the highest dose used (50 µg g-1 body mass), affecting plasma and hepatic metabolites. Our results demonstrated that Aroclor 1254 compromises the hypoosmoregulatory function of vasotocinergic system in S. aurata, also inducing a concomitant stress response. In summary, this study demonstrates that Aroclor 1254 can be considered an important endocrine disruptor in relation with the correct arrangement of vasotocinergic, metabolic and stress pathways after their stimulation by transfer to hyperosmotic environments.


Assuntos
/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Osmorregulação/efeitos dos fármacos , Dourada/fisiologia , Estresse Fisiológico/efeitos dos fármacos , Animais , Proteínas de Peixes/genética , Hidrocortisona/sangue , Hipotálamo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
12.
Gen Comp Endocrinol ; 280: 73-81, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981702

RESUMO

Evidence has shown that neuromedin S (NMS) and its receptor (NMU2R) are expressed in the hypothalamus, pituitary, and testis of pigs. To determine the potential mechanisms of NMS, we systematically investigated the direct effects of NMS on the hypothalamic-pituitary-testicular (HPT) axis of male pigs in vitro. We initially confirmed that NMU2R distributed in isolated hypothalamic cells, anterior pituitary cells and Leydig cells using immunocytochemistry. Subsequently we investigated the direct effects of NMS on hormone secretion from cells (anterior pituitary cells and Leydig cells) treated with different doses of NMS. The results showed that NMS increase the release of LH and FSH from anterior pituitary cells and testosterone from Leydig cells. NMS up-regulated the expression of NMU2R and GnRH mRNAs in hypothalamic cells, NMU2R, LH and FSH mRNAs in anterior pituitary cells, and NMU2R, STAR, P450 and 3ß-HSD mRNAs and the expression of PCNA and Cyclin B1 protein in Leydig cells; moreover, it down-regulated the expression of GnIH mRNA in hypothalamic cells. Using immunofluorescence staining and confocal microscopy, we also demonstrated the colocalization of NMU2R and AR or GnIH in Leydig cells. These data in vitro indicated that NMS may regulate the release and/or synthesis of LH, FSH and testosterone at different levels of the reproductive axis through NMU2R, which provided novel evidence of the potential roles of NMS in regulation of pig reproduction.


Assuntos
Hipotálamo/metabolismo , Neuropeptídeos/farmacologia , Hipófise/metabolismo , Testículo/metabolismo , Animais , Ciclina B1/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Hipófise/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Neurotransmissores/metabolismo , Suínos , Testículo/efeitos dos fármacos , Testosterona/metabolismo
13.
Pituitary ; 22(4): 353-361, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989445

RESUMO

PURPOSE: Deteriorated pituitary function can lead to serious complications that might need lifelong hormone replacement therapy. However, long-term hormone administration can have significant adverse effects. Thus, it would be more desirable to restore pituitary function by pituitary transplantation. In this study, we investigated functional preservation of extracted pituitary gland in special preservation solution under hypothermic condition for pituitary transplantation. METHODS: We obtained nineteen pituitary glands from 250-300 g male Sprague-Dawley rats via parapharyngeal approach. These extracted glands were divided into three pieces and stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C and compared to their corresponding glands stored in phosphate buffer saline (PBS). Light and electron microscopic examinations were performed to identify morphological changes of pituitary gland at 0,3, and 7 days after storage. TUNEL assay to confirm cell viability, and adenosine-triphosphate (ATP) concentration were also serially examined. RESULTS: Tissue architecture and cellular viability of specimens preserved in HTK solution for 3 days were considerably maintained and similar to those in normal pituitary gland (0 day specimen). In contrast, specimens stored in PBS were markedly destroyed after 3 days of storage. After 7 days of storage, significant degeneration occurred in tissues stored in both HTK and PBS. However, tissue architecture was preserved more in specimens stored in HTK solution than those stored in PBS. ATP concentration decreased more rapidly in specimens stored in PBS solution, but there was no statistical significance (p= 0.055). CONCLUSIONS: Extracted rat pituitary gland supplemented with special preservation solution could be preserved for 3 days under hypothermic condition.


Assuntos
Preservação de Órgãos/métodos , Hipófise/citologia , Hipófise/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Histidina/farmacologia , Ácidos Cetoglutáricos/farmacologia , Masculino , Hipófise/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Triptofano/farmacologia
14.
Gen Comp Endocrinol ; 280: 134-146, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31015009

RESUMO

Gonadotropin-releasing hormone 2 (Gnrh2) is one of the three classes of Gnrh distributed in vertebrates and is highly conserved. In the present study, the cDNA encoding Gnrh2 was isolated and characterized in the ostariophysan catfish Heteropneustes fossilis (hf). The cDNA is 611 bp long with an open reading frame (ORF) of 261 bp that encodes a highly conserved protein of 86 amino acids. The deduced Gnrh2 precursor protein clustered with the vertebrate Gnrh2 type. The sequence identity of hfgnrh2 is 94% with African catfish (Clarias gariepinus) gnrh2 mRNA (accession no. X78047). The hfgnrh2 transcripts were expressed only in the brain and gonads with a higher expression in the female brain and ovary in both resting and prespawning phases. The expression was higher in the prespawning phase than the resting phase. The gnrh2 expression in the brain and ovary showed significant seasonal variations but with opposite patterns. In the brain, the expression was the highest in the preparatory phase, decreased progressively to low levels in the postspawning and resting phases. In the ovary, the transcript level was low in the resting and preparatory phases, increased sharply in the prespawning phase reaching the peak level in the spawning phase and declined sharply in the postspawning phase. The gnrh2 mRNA showed the highest expression in the hind brain-medulla oblongata and moderate to low expression in forebrain regions and pituitary. Ovariectomy resulted in a duration-dependent inhibition of hfgnrh2 mRNA levels in the resting and prespawning phases. Steroid (E2, testosterone and progesterone) replacement treatments (0.5 µg/g body weight) in the 3- week ovariectomized fish restored the inhibition due to ovariectomy, elevated the expression over and above the sham level in the resting phase (E2 group), and raised the levels almost to that of the sham group (testosterone and progesterone groups) in the prespawning phase. In the sham control groups, the steroid replacement resulted in a significant reduction in the mRNA levels. The expression of the gnrh2 mRNA in the brain-pituitary-gonadal axis and its regulation by gonadal steroids suggest that Gnrh2 may have a reproductive role in the catfish.


Assuntos
Peixes-Gato/genética , DNA Complementar/genética , Ovário/metabolismo , Esteroides/farmacologia , Sequência de Aminoácidos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Clonagem Molecular , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Ovariectomia , Ovário/efeitos dos fármacos , Filogenia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estações do Ano , Caracteres Sexuais , Testosterona/metabolismo
15.
Am J Physiol Endocrinol Metab ; 316(6): E1036-E1049, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30888862

RESUMO

Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice. This correlated with increased levels of GH, prolactin, and the cells that secrete these hormones, somatotropes and lactotropes, respectively, in Jekyll pituitaries. Recombinant myostatin also stimulated GH release and gene expression in pituitary cell cultures although inhibiting prolactin release. In primary hepatocytes, recombinant myostatin blocked GH-stimulated expression of two key mediators of growth, insulin-like growth factor (IGF)1 and the acid labile subunit and increased expression of an inhibitor, IGF-binding protein-1. The significance of these findings was demonstrated by smaller muscle fiber size in a model lacking myostatin and liver IGF1 expression (LID-o-Mighty mice) compared with that in myostatin-null (Mighty) mice. These data together suggest that myostatin may regulate pituitary development and function and that its inhibitory actions in muscle may be partly mediated by attenuating GH action in the liver. They also suggest that circulating pharmacological inhibitors of myostatin could produce unintended consequences in these and possibly other tissues.


Assuntos
Hormônio do Crescimento/metabolismo , Hepatócitos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lactotrofos/metabolismo , Miostatina/genética , Hipófise/crescimento & desenvolvimento , Prolactina/metabolismo , Somatotrofos/metabolismo , Animais , Caquexia , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Desenvolvimento de Medicamentos , Glicoproteínas/efeitos dos fármacos , Glicoproteínas/metabolismo , Hormônio do Crescimento/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Lactotrofos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Knockout , Modelos Animais , Miostatina/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Cultura Primária de Células , Prolactina/efeitos dos fármacos , Proteínas Recombinantes , Somatotrofos/efeitos dos fármacos , Células-Tronco
16.
Ecotoxicol Environ Saf ; 174: 224-235, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30844666

RESUMO

In recent years, decabromodiphenyl ethane (DBDPE), a new alternative flame retardant to the decabrominated diphenyl ethers (BDE-209), is widely used in a variety of products. Previous studies have indicated that DBDPE, like BDE-209, could disrupt thyroid function. However, compared with BDE-209, the degrees of thyrotoxicosis induced by DBDPE were not clear. In addition, the mechanism of thyrotoxicosis induced by DBDPE or BDE-209 was still under further investigation. In this study, male rats as a model were orally exposed to DBDPE or BDE-209 by 5, 50, 500 mg/kg bw/day for 28 days. Then, we assessed the thyrotoxicosis of DBDPE versus BDE-209 and explored the mechanisms of DBDPE and BDE-209-induced thyrotoxicosis. Results showed that decreased free triiodothyronine (FT3) and increased thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) in serum were observed in both 500 mg/kg bw/day BDE-209 and DBDPE group. Decreased total thyroxine (TT4), total T3 (TT3), and free T4 (FT4) were only observed in BDE-209 group but not in DBDPE group. Histological examination and transmission electron microscope examination showed that high level exposure to BDE-209 and DBDPE both caused significant changes in histological structure and ultrastructure of the thyroid gland. Additionally, oxidative damages of thyroid gland (decreased SOD and GSH activities, and increased MDA content) were also observed in both BDE-209 and DBDPE groups. TG contents in the thyroid gland was reduced in BDE-209 group but not in DBDPE group. Both BDE-209 and DBDPE affected the expression of hypothalamic-pituitary-thyroid (HPT) axis related genes. These findings suggested that both BDE-209 and DBDPE exposure could disrupt thyroid function in the direction of hypothyroidism and the underlying mechanism was likely to be oxidative stress and perturbations of HPT axis. However, DBDPE was found to be less toxic than BDE-209.


Assuntos
Bromobenzenos/toxicidade , Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Glândula Tireoide/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Ratos , Ratos Sprague-Dawley , Glândula Tireoide/metabolismo , Glândula Tireoide/ultraestrutura , Tireotropina/sangue , Hormônio Liberador de Tireotropina/sangue , Tri-Iodotironina/sangue
17.
Neuroscience ; 406: 268-277, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30880102

RESUMO

Photoperiod and diet are factors known to modulate the hypothalamic-pituitary-adrenal (HPA) axis. Specifically, shifts in photoperiod have been previously linked with affective and anxiety disorders. Furthermore, isoflavones have been shown to mediate behavioral outcome in response to the environment of the animal. Here, we investigated the effect of photoperiod alteration on the HPA axis and how the addition of isoflavones might modulate the response to stress. Male C57BL/6J mice were maintained on either a 12:12 or a 16:8 light-dark (LD) cycle for 10 days, and fed a diet of either standard rodent chow or an isoflavone free (IF) chow beginning 3 weeks prior to light alteration. Consistent with previous work, mice in the shorter active period (16:8 LD cycle) showed increased basal corticosterone (CORT) secretion. In the absence of isoflavones, this response was attenuated. Increases in mineralcorticoid (MR) and glucocorticoid (GR) receptor mRNA expression were seen in the pituitary following photoperiod alteration. However, animals fed the standard isoflavone rich chow showed increases in the ratio of MR:GR mRNA in the anterior bed nucleus of the stria terminalis following photoperiod alteration. Decreases in corticotrophin-releasing factor receptor 1 (CRFR1) mRNA expression were seen in animals fed the IF chow in the amygdala, prefrontal cortex and ventral hippocampus. These data suggest that alterations in CORT secretion following photoperiod alteration may be mediated through differences in CRFR1 gene expression or changes in MR:GR mRNA ratios. These findings provide insight into the potential mechanisms by which the HPA axis adapts to photoperiod and diet.


Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Isoflavonas/farmacologia , Fotoperíodo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Hormônio Adrenocorticotrópico/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hipófise/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Estresse Psicológico/tratamento farmacológico
18.
Gen Comp Endocrinol ; 275: 65-72, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30769010

RESUMO

The pituitary is a central organ of the neuro-endocrine system in fish that plays critical roles in various physiological processes, including stress response and behavior. Although it is known that pituitary hormones can have a direct or indirect influence stimulating or suppressing the immune responses, whether there is a local immune response in the pituitary or what is the effect of the immune stimulus on the pituitary function in fish is unknown. With the aim to understand the interaction between the immune responses and the endocrine axes at the pituitary level, particularly the Hypothalamus-Pituitary-Interrenal (HPI) axis, pituitaries of rainbow trout (Oncorhynchus mykiss) were cultured in vitro, incubated with bacterin, or bacterin plus CRH, cortisol, human recombinant IL1ß, or spleen medium for 3 h, and then genes involved in pro-inflammation (il1ß, il8, tnfα1, ifnγ), anti-inflammation (tgfß1b, il10), immune modulation (mhcIIa, c3, mif) and stress response (crhbp, pomca, pomcb, gr1) were tested. Data showed that, incubation with bacterin alone and bacterin plus recombinant IL1ß or CRH, as well as medium from bacterin treated spleen caused significant up-regulation of pro-inflammatory genes il1ß and il8, while down-regulated the anti-inflammatory gene tgfß1b. Besides, recombinant IL1ß plus bacterin or alone caused raise of mhcIIa and tnfa, respectively. On the contrary, just a slight or even no alteration was recorded in the expression of stress response genes including crhbp, pomca, pomcb and gr1 in the in vitro cultured trout pituitary following this stimulation. These results suggest a local immune gene equipment in the pituitary of fish, and the potential for fish pituitary to develop both innate and adaptive immune responses, whereas that immune stimulation was not able to evoke a significant endocrine stress response in vitro.


Assuntos
Vacinas Bacterianas/farmacologia , Imunidade Ativa/efeitos dos fármacos , Oncorhynchus mykiss/imunologia , Hipófise/efeitos dos fármacos , Vibrio/imunologia , Animais , Anti-Inflamatórios/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrocortisona/metabolismo , Mediadores da Inflamação/metabolismo , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , Técnicas de Cultura de Órgãos , Hipófise/citologia , Hipófise/imunologia , Hipófise/metabolismo
19.
Food Chem ; 283: 422-430, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30722893

RESUMO

The endocrine system is highly sensitive to endocrine-disrupting chemicals (EDC) which interfere with metabolism, growth and reproduction throughout different periods of life, especially in the embryonic and pubertal stages, in which gene reprogramming may be associated with impaired development and control of tissues/organs even in adulthood. Acrylamide is considered a potential EDC and its main source comes from fried, baked and roasted foods that are widely consumed by children, teenagers and adults around the world. This review aimed to present some aspects regarding the acrylamide formation, its toxicokinetics, the occurrence of acrylamide in foods, the recent findings about its effects on different systems and the consequences for the human healthy. The challenges to characterize the molecular mechanisms triggered by acrylamide and to establish safe levels of consumption and/or exposure are also discussed in the present review.


Assuntos
Acrilamida/toxicidade , Disruptores Endócrinos/toxicidade , Sistema Nervoso/efeitos dos fármacos , Acrilamida/química , Acrilamida/farmacocinética , Animais , Criança , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacocinética , Humanos , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/metabolismo , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Reprodução/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo
20.
Neuroscience ; 406: 606-616, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30797025

RESUMO

Protracted radioiodine release may require repeated intake of potassium iodide (KI) to protect thyroid gland. It is well established that iodine excess inhibits transiently the thyroid function. As developing fetus depends on maternal thyroid hormones (TH) supply, more knowledge is needed about the plausible effects that repeated KI intake can cause in this sensitive population, especially that even subtle variation of maternal thyroid function may have persistent consequences on progeny brain processing. The aim of this study is to assess the consequences of repeated intake of KI during pregnancy on the progeny's thyroid function and brain development. To do so pregnant Wistar rats received KI over eight days, and then thirty days after the weaning, male progeny was subjected to behavior test. Pituitary and thyroid hormones level, anti-thyroid antibodies level, organs morphology, gene expression and global DNA methylation were assessed. Thirty days after the weaning, KI-exposed male progeny showed an uncommon hormonal status, characterized by a decrease of both thyroid-stimulating hormone (-28%) and free thyroxine (-7%) levels. Motor coordination was altered in KI-exposed male progeny. At the cerebellar level, we observed a decrease of mRNA expression of DCX (-42%) and RC3 (-85%); on the other hand, at the cortical level, mRNA expression of MBP (+71%), MOBP (+90%) and Kcna1 (+42%) was increased. To conclude, repeated KI prophylaxis is not adequate during pregnancy since it led to long-term irreversible neurotoxicity in the male progeny.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Hipófise/efeitos dos fármacos , Iodeto de Potássio/farmacologia , Animais , Encéfalo/metabolismo , Feminino , Radioisótopos do Iodo , Gravidez , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo
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