[PMID]: | 28471544 |
[Au] Autor: | Sarkar D; Singh SK |
[Ad] Endereço: | Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India. |
[Ti] Título: | Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43. |
[So] Source: | Andrology;5(4):749-762, 2017 07. |
[Is] ISSN: | 2047-2927 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose homeostasis via increased oxidative stress in prepubertal mice, thereby affecting germ cell survival and proliferation. |
[Mh] Termos MeSH primário: |
Conexina 43/metabolismo Proteínas Facilitadoras de Transporte de Glucose/metabolismo Transportador de Glucose Tipo 3/metabolismo Glucose/metabolismo Hipotireoidismo/metabolismo Estresse Oxidativo Testículo/metabolismo
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[Mh] Termos MeSH secundário: |
Fatores Etários Animais Animais Recém-Nascidos Antioxidantes/metabolismo Apoptose Proliferação Celular Conexina 43/genética Modelos Animais de Doenças Regulação para Baixo Homeostase Hipotireoidismo/induzido quimicamente Hipotireoidismo/genética Hipotireoidismo/patologia L-Lactato Desidrogenase/metabolismo Ácido Láctico/metabolismo Peroxidação de Lipídeos Masculino Camundongos Antígeno Nuclear de Célula em Proliferação/metabolismo Propiltiouracila Testículo/patologia Fatores de Tempo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Antioxidants); 0 (Connexin 43); 0 (GJA1 protein, mouse); 0 (Glucose Transport Proteins, Facilitative); 0 (Glucose Transporter Type 3); 0 (Proliferating Cell Nuclear Antigen); 0 (Slc2a3 protein, mouse); 0 (Slc2a8 protein, mouse); 33X04XA5AT (Lactic Acid); 721M9407IY (Propylthiouracil); EC 1.1.1.27 (L-Lactate Dehydrogenase); IY9XDZ35W2 (Glucose) |
[Em] Mês de entrada: | 1801 |
[Cu] Atualização por classe: | 180227 |
[Lr] Data última revisão:
| 180227 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170505 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1111/andr.12363 |
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