Laboratory of Comparative Endocrinology, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
Neuroscience. 2012 Sep 27;221:69-85. doi: 10.1016/j.neuroscience.2012.06.057. Epub 2012 Jul 4.
Maternal thyroid hormones (THs) are important in early brain development long before the onset of embryonic TH secretion, but information about the regulation of TH availability in the brain at these early stages is still limited. We therefore investigated in detail the mRNA distribution pattern of the TH activating type 2 and inactivating type 3 deiodinases (D2 and D3) and the TH transporters, organic anion transporting polypeptide 1c1 (Oatp1c1) and monocarboxylate transporter 8 (Mct8), in chicken embryonic brain as well as in retina and inner ear from day 3 to day 10 of development. Oatp1c1, Mct8 and D3 are expressed in the choroid plexus and its precursors allowing selective uptake of THs at the blood-cerebrospinal fluid-barrier with subsequent inactivation of excess hormone. In contrast, the developing blood-brain-barrier does not express Oatp1c1 or Mct8 but appears to be a site for TH activation by D2. Expression of D3 in several sensory brain centers may serve as protection against premature TH action. Expression of D2 and Mct8 but not D3 in the developing pituitary gland allows accumulation of active THs even at early stages. Mct8 is widely expressed in gray matter throughout the brain. This is the first comprehensive study on the dynamic distribution pattern of TH-transporters and deiodinases at stages of embryonic brain development when only maternal THs are available. It provides the essential background for further research aimed at understanding early developmental processes depending on maternal THs.
母体甲状腺激素(THs)在胚胎 TH 分泌之前的早期大脑发育中起着重要作用,但关于这些早期阶段大脑中 TH 可利用性的调节信息仍然有限。因此,我们详细研究了 TH 激活型 2 型和失活型 3 型脱碘酶(D2 和 D3)以及 TH 转运蛋白有机阴离子转运多肽 1c1(Oatp1c1)和单羧酸转运蛋白 8(Mct8)在鸡胚胎大脑中的 mRNA 分布模式,以及从第 3 天到第 10 天发育过程中的视网膜和内耳。Oatp1c1、Mct8 和 D3 在脉络丛及其前体中表达,允许 TH 选择性地在血脑屏障处摄取,随后对多余的激素进行失活。相比之下,正在发育的血脑屏障不表达 Oatp1c1 或 Mct8,但似乎是 D2 激活 TH 的部位。几种感觉性脑中心的 D3 表达可能是防止 TH 过早作用的一种保护机制。D2 和 Mct8 但不是 D3 在发育中的垂体中表达,即使在早期阶段也允许积累活性 TH。Mct8 在大脑中的灰质中广泛表达。这是在仅存在母体 THs 的胚胎大脑发育阶段对 TH 转运蛋白和脱碘酶的动态分布模式进行的首次全面研究。它为进一步研究依赖于母体 THs 的早期发育过程提供了必要的背景。