Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Thyroid. 2013 Apr;23(4):497-505. doi: 10.1089/thy.2011.0514. Epub 2013 Mar 18.
Studies in men are not consistent regarding the effects of thyroid hormone on the production of gonadotropins. In hypothyroidism consequent to diverse causes, an increase or no change in serum luteinizing hormone (LH) have been reported. The attempt to explain the mechanisms involved in this pathology using rats as an experimental model also seems to repeat this divergence, since hypothyroidism has been shown to induce hypogonadotropic hypogonadism, a hypergonadotropic state, or not to affect the basal levels of LH. Notably, the promoter region of the gene encoding the Lh beta subunit and GnRH (gonadotropin-releasing factor) does not contain a thyroid responsive element. Therefore, we investigated the hypothesis that, in male rats, posttranscriptional mechanisms of LH synthesis are altered in hypothyroidism. We also attempted to determine if hypothyroidism directly affects testicular function in male rats.
Male Wistar rats, 60 days old, were thyroidectomized or sham-operated. After 20 days, they were decapitated, and the pituitaries were collected and analyzed for Lh mRNA, LH content, poly(A) tail length, and polysome profile. The testes were collected and analyzed for Lh receptor mRNA, LH receptor content, and histology using morphometric analyses. The testis, epididymis, seminal vesicle, and ventral prostate were weighed, and serum concentrations of LH, testosterone, thyrotropin (TSH), and triiodothyronine (T3) were measured.
Hypothyroidism was associated, in the pituitary, with an increase in Lh mRNA expression, a reduction in Lh mRNA poly(A) tail length, a reduction in the number of LH transcripts associated with polysomes. Pituitary LH was decreased but serum LH was increased from 102 to 543 pg/mL. Despite this, serum testosterone concentrations were decreased from 1.8 to 0.25 ng/mL. A decreased germinative epithelium height of the testes and a reduced weight of androgen-responsive tissues were observed (ventral prostrate: 74 vs. 23 mg/100 g body weight [BW]; seminal vesicle undrained: 280 vs. 70 mg/100 g BW; and seminal vesicle drained: 190 vs. 60 mg/100 g BW).
Hypothyroidism in adult male rats has dual effects on the pituitary testicular axis. It alters posttranscriptional mechanisms of LH synthesis and probably has a direct effect on testicular function. However, these data suggest the possibility that reduced LH bioactivity may account in part for impaired testicular function.
关于甲状腺激素对促性腺激素产生的影响，男性的研究结果并不一致。在由多种原因引起的甲状腺功能减退症中，血清黄体生成素（LH）的增加或无变化已有报道。尝试使用大鼠作为实验模型来解释该病理机制中涉及的机制似乎也存在这种分歧，因为甲状腺功能减退症已被证明会导致促性腺激素低下的性腺功能减退症、促性腺激素亢进状态，或者不会影响 LH 的基础水平。值得注意的是，编码 Lhβ亚基和 GnRH（促性腺激素释放因子）的基因启动子区域不包含甲状腺反应元件。因此，我们假设在雄性大鼠中，甲状腺功能减退症会改变 LH 合成的转录后机制。我们还试图确定甲状腺功能减退症是否直接影响雄性大鼠的睾丸功能。
60 天大的雄性 Wistar 大鼠行甲状腺切除术或假手术。20 天后，断头处死大鼠，收集垂体进行 LH mRNA、LH 含量、多聚（A）尾长和多核糖体谱分析。收集睾丸进行 LH 受体 mRNA、LH 受体含量和组织学分析，使用形态计量学分析。测量睾丸、附睾、精囊和前列腺重量以及血清 LH、睾酮、促甲状腺素（TSH）和三碘甲状腺原氨酸（T3）浓度。
甲状腺功能减退症与垂体中 LH mRNA 表达增加、LH mRNA 多聚（A）尾长减少以及与多核糖体结合的 LH 转录物数量减少有关。垂体 LH 减少，但血清 LH 从 102 增加到 543 pg/ml。尽管如此，血清睾酮浓度从 1.8 降低到 0.25 ng/ml。观察到睾丸生精上皮高度降低和雄激素反应组织重量减少（前列腺：74 与 23 mg/100 g 体重[BW]；未排空精囊：280 与 70 mg/100 g BW；排空精囊：190 与 60 mg/100 g BW）。
成年雄性大鼠的甲状腺功能减退症对垂体-睾丸轴有双重影响。它改变了 LH 合成的转录后机制，并且可能对睾丸功能有直接影响。然而，这些数据表明，LH 生物活性降低可能部分解释了睾丸功能受损的原因。
