Chronobiology Research Group, Department of Health Sciences, State University of Santa Cruz, Ilhéus, Brazil.
Reproduction and Endocrinology Research Center, Department of Biological Sciences, State University of Santa Cruz, Ilhéus, Brazil.
Front Endocrinol (Lausanne). 2024 Aug 1;15:1322867. doi: 10.3389/fendo.2024.1322867. eCollection 2024.
The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of and in the pineal gland and gonads of rats with hypothyroidism at different times of the day.
Female and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes ( and ) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs.
The results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and expression in the gonads.
This study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes ( and ) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner.
生殖系统受到环境和生理信号的严密调控。褪黑素，作为黑暗的荷尔蒙，在哺乳动物的昼夜节律和生殖系统中发挥着关键作用。甲状腺功能减退症是一种重要的内分泌紊乱疾病，会对生殖系统造成损害。尽管有许多关于褪黑素对生殖系统影响的研究，但褪黑素合成在甲状腺功能减退症中的调节作用存在相互矛盾的信息。本研究旨在探讨不同时间点甲状腺功能减退症大鼠松果体和性腺中褪黑素水平和基因表达的变化。
将雌性和雄性 Wistar 大鼠分为对照组和甲状腺功能减退组。使用丙基硫氧嘧啶（PTU）诱导甲状腺功能减退症 15 天，大鼠在光照后 6 小时（ZT6）、光照前 11.5 小时（ZT11.5）和光照后 6 小时（ZT18）处死。测定血浆中的游离甲状腺素（FT4）和褪黑素含量，测定松果体和性器官（睾丸和卵巢）中褪黑素合成酶（和）的基因表达。还对性器官进行形态学分析。
结果显示，两性之间存在一些差异。甲状腺功能减退症减少了卵巢中的窦前卵泡和初级卵泡，并降低了睾丸、附睾和前列腺的重量。就基因表达而言，我们观察到光照期（ZT6）松果体中表达减少，而在雄性中，这种减少发生在暗期（ZT18）。关于 表达，在女性中，在暗期（ZT18）也有所下降。在性腺中，两性在 ZT11.5 时表达增加。此外，观察到 FT4 水平与性腺中 表达之间的关联很有趣。
本研究表明，急性甲状腺功能减退症会影响生殖系统中褪黑素系统的组成部分，特别是褪黑素合成酶（和）的基因表达，这会导致疾病进展过程中生殖器官发生变化。这些发现增强了我们对甲状腺功能减退症期间生殖系统中褪黑素合成的理解，表明雄性和雌性大鼠的反应不同，并表明甲状腺功能减退症以性别依赖的方式影响褪黑素合成的昼夜节律性。
