Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, via Vivaldi, 43, 81100 Caserta, Italy.
J Endocrinol. 2013 Sep 9;219(1):69-78. doi: 10.1530/JOE-13-0127. Print 2013 Oct.
The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor (Trα (Thra) and Trβ (Thrb)) are expressed in rat HGs. Although Thra is expressed at a higher level, only Thrb is regulated by triiodothyronine (T3). Because T3 induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of T3 to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T3 modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by ∼50% in hypothyroid T3-treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1 and Tfam, whereas T3 treatment increased the expression level of these genes.
大鼠哈德腺（HG）是一种眶内腺体，可分泌大量脂质分泌物。最近的研究表明，其分泌活动受甲状腺激素调节。在这项研究中，我们发现甲状腺激素受体（Trα（Thra）和 Trβ（Thrb））的两种同工型均在大鼠 HG 中表达。虽然 Thra 的表达水平较高，但只有 Thrb 受三碘甲状腺原氨酸（T3）调节。由于 T3 可诱导大鼠 HG 中的脂质代谢增加，因此我们研究了动物甲状腺状态对肉毒碱棕榈酰基转移酶-1A（Cpt1a）和肉毒碱棕榈酰基转移酶-1B（Cpt1b）以及酰基辅酶 A 氧化酶（Acox1）（分别为线粒体和过氧化物酶体脂肪酸氧化的限速酶）表达水平的影响，以及对线粒体区室的影响，从而将线粒体活性和生物发生与形态分析相关联。我们发现，甲状腺功能减退症降低了 Cpt1b 和 Acox1 mRNA 的表达，而向甲状腺功能减退症大鼠给予 T3 则增加了转录水平。呼吸参数和过氧化氢酶蛋白水平提供了进一步的证据，表明 T3 调节线粒体和过氧化物酶体的活性。此外，在甲状腺功能减退症大鼠的 HG 中，与对照组相比，线粒体数量及其总面积减少，而单个线粒体的平均面积没有变化。然而，在甲状腺功能减退症 T3 治疗的 HG 中，单个线粒体的平均面积减少了约 50％，并且线粒体数量和线粒体区室的总面积增加。线粒体形态计量学数据与分子结果很好地相关。实际上，甲状腺功能减退症状态不会改变线粒体生物发生基因（如 Ppargc1a、Nrf1 和 Tfam）的表达，而 T3 处理则增加了这些基因的表达水平。
