Thyroid Hormone Export Varies among Primary Cells and Appears to Differ from Hormone Uptake

Neves, Francisco Assis Rocha

doi:10.1210/en.143.2.476

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…Several membrane transporter families have been identified, however only monocarboxylate transporter (MCT) 8, MCT 10 and organic anion-transporting polypeptides (OATPs) demonstrate a high degree of specificity towards thyroid hormone (22). The OATPs form a novel family of transporter proteins that have been detected in several tissues, including testis, in rodents and humans (22)(23)(24)(25)(26)(27)(28).…”

Section: Clinical Implications Of Altered Thyroid Functionmentioning

confidence: 99%

Clinical implications of altered thyroid status in male testicular function

Wajner

Wagner

Maia

2009

Arq Bras Endocrinol Metab

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Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function. RESUMOOs hormônios da tireoide estão envolvidos virtualmente no desenvolvimento e na manutenção de todos os tecidos. As gônadas masculinas foram, por décadas, consideradas insensíveis aos hormônios tireoidianos. No entanto, estudos mais recentes têm demonstrado que disfunções tireoidianas estão associadas não somente a anormalidades na morfologia e na função dos testículos, mas também à diminuição da fertilidade e alterações na atividade sexual masculina. Atualmente, o papel da triiodotironina (T3) no controle da proliferação das células de Sertoli e Leydig, maturação testicular e esteroidogênese é amplamente aceito, bem como a presença de transportadores e receptores para o hormônio tireoidiano nos testículos durante o período de desenvolvimento e a idade adulta. No entanto, apesar dos dados que indicam que o T3 atua diretamente nos testículos humanos, persistem controvérsias em relação ao impacto das doenças tireoidianas sobre a espermatogênese e a fertilidade, o que pode ser em parte devido à escassez de estudos clínicos nessa área. Essa revisão tem por objetivo apresentar um panorama de dados clínicos atualizados sobre o papel dos hormônios tireoidianos na função gonadal masculina. Arq Bras Endocrinol Metab. 2009;53(8):976-82 Descritores

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Section: Clinical Implications Of Altered Thyroid Functionmentioning

confidence: 99%

Clinical implications of altered thyroid status in male testicular function

Wajner

Wagner

Maia

2009

Arq Bras Endocrinol Metab

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“…It pumps substrates in one direction, typically out of the cytoplasm. Several studies have attempted to examine the interaction of thyroid hormones with MDR proteins (Nelson & Hinkle 1992, Ribeiro et al 1996, Cavalieri et al 1999, Neves et al 2002. Inhibition of thyroid hormone efflux by verapamil has been reported in several cell types (Ribeiro et al 1996, Neves et al 2002.…”

Section: Discussionmentioning

confidence: 99%

“…While previous studies provided some evidence suggesting interaction between MDR proteins and thyroid hormone export from cells, they either used drug-selected cell lines (Ribeiro et al 1996) or primary cells (Neves et al 2002) that expressed multiple MDR transporters in addition to P-gp. In addition, the calcium channel blocker verapamil, which is not selective for MDR, was used as an inhibitor of MDR transport.…”

Section: Discussionmentioning

confidence: 99%

“…P-gp pumps substrates in a single direction, out of cytoplasm, and is present in high levels in many multidrug-resistant cell lines and tumors. Verapamil-sensitive thyroid hormone efflux from cells has been reported in several cell types (Ribeiro et al 1996, Neves et al 2002 and, as verapamil is a potent inhibitor of P-gp, this suggested involvement of the MDR transporters in the efflux of thyroid hormone. Verapamil is not, however, a specific inhibitor of P-gp and it was also found to inhibit tri-iodothyronine (T 3 ) efflux from cells that did not express MDR1 (Cavalieri et al 1999).…”

Section: Introductionmentioning

confidence: 87%

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Thyroid hormone export from cells: contribution of P-glycoprotein

Mitchell

Tom²,

Mortimer³

2005

Journal of Endocrinology

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Verapamil inhibits tri-iodothyronine (T 3 ) efflux from several cell types, suggesting the involvement of multidrug resistance-associated (MDR) proteins in T 3 transport. The direct involvement of P-glycoprotein (P-gp) has not, however, been investigated. We compared the transport of compared with MDCKII cells, probably reflecting enhanced export of T 3 from MDCKII-MDR cells rather than reduced cellular uptake, as P-gp typically exports substances from cells. Verapamil lowered the rate of 125 I-T 3 efflux from both MDCKII and MDCKII-MDR cells by 42% and 66% respectively, while nitrendipine reduced 125 I-T 3 efflux rate by 36% and 48% respectively, suggesting that both substances inhibited other cellular T 3 transporters in addition to P-gp. The specific MDR inhibitors VX 853 and VX 710 had no effect of 125 I-T 3 efflux rate from wild-type MDCKII cells but reduced 125 I-T 3 export in MDCKII-MDR cells by 50% and 53% respectively. These results have provided the first direct evidence that P-gp exports thyroid hormone from cells. (2005) 185, [93][94][95][96][97][98] Journal of Endocrinology

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“…A diminuição da concentração de T 3 intracelular nestas células foi devida ao aumento do seu efluxo pela membrana plasmática (35). Experimentos posteriores em células de tireóide de ratos (FRTL-5), fibroblastos de camundongos (NIH-3T3) e em células primárias de átrio, ventrículo, rim e placenta mostraram que, tanto o influxo quanto o efluxo de HT, variam consideravelmente entre os diversos tecidos (35)(36)(37). Além disso, o transporte de HTs pode compensar a diminuição de seus níveis plasmáti-cos observada, por exemplo, em pacientes com insuficiência renal crônica.…”

Section: Transporte Dos Hormônios Tireoideanosunclassified

Mecanismo molecular da ação do hormônio tireoideano

Barra

Velasco

Pessanha

et al. 2004

Arq Bras Endocrinol Metab

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RESUMOOs hormônios tireoideanos (HTs) são necessários para a diferenciação, crescimento e metabolismo de diversos tecidos de vertebrados. Seus efeitos são mediados pelos receptores do hormônio tireoideano (TRs), membros da superfamília dos receptores nucleares. Estes receptores são fatores de transcrição modulares que se ligam em seqüências específi-cas do DNA denominadas elementos responsivos ao TR, que são encontrados nos promotores dos genes regulados pelo HT. Os TRs são codificados por dois genes distintos, α e β, localizados nos cromossomos 17 e 3, respectivamente. Estas isoformas apresentam diferentes funções e sua expressão é específica para cada tecido. O TR se liga ao DNA como monômero, homodímero ou heterodímero com o receptor de retinóide X (RXR). Além disso, o TR modula a atividade transcricional (repressão ou ativação) através da interação com correpressores e co-ativadores, na ausência e na presença do T 3 , respectivamente. A compreensão do mecanismo molecular da ação do receptor do hormônio tireoideano e a definição de sua estrutura cristalográfica contribuirão para a aquisição de novos conceitos envolvidos na transcrição e nos distúrbios hormonais presentes nas doenças endócrinas, assim como facilitará o desenho de novas drogas, agonistas ou antagonistas, com grande valor terapêutico. Thyroid hormones (TH) are involved in normal differentiation, growth, and metabolism in several tissues of all vertebrates. Their actions are mediated by the TH receptors (TRs), members of the nuclear hormone receptor superfamily. These receptors are transcription factors that bind to DNA on specific sequences, the TR response element (TREs), in promoters of target genes. Two genes encode TRs, α e β, located in chromosomes 17 and 3, respectively. These isoforms show different functions and exhibit a tissue specific expression. TRs function as monomers, homodimers or heterodimers with retinoid X receptor (RXR) and modulate transcription activity (repression or activation) by interacting with co-repressor and coactivators, which associate with TR in the absence or presence of T 3 , respectively. Understanding the molecular mechanism of TR action and the definition of its crystallographic structure will provide new insights into transcription mechanisms and will facilitate the design of new drugs with greater therapeutic value.

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Thyroid Hormone Export Varies among Primary Cells and Appears to Differ from Hormone Uptake

Cited by 9 publications

References 37 publications

Clinical implications of altered thyroid status in male testicular function

Clinical implications of altered thyroid status in male testicular function

Thyroid hormone export from cells: contribution of P-glycoprotein

Mecanismo molecular da ação do hormônio tireoideano

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