Telomerase, a ribonucleoprotein responsible for telomere re-elongation, is important for male and female fertility. Several factors, including the steroid hormone estrogen, regulate the expression of Telomerase Reverse Transcriptase (TERT), which one of its non-canonical functions is gene expression regulation. The steroidogenesis process is regulated principally by transcription of genes encoding steroidogenic enzymes, but it is not clear if TERT non-canonical functions affect the expression of steroidogenic genes. Here we investigated this new notion by increasing TERT expression and activity in granulosa cells (GCs) derived from rat and from women that underwent in vitro fertilization (IVF) procedures and in vivo in mouse ovary. We show that gonadotropin enhanced the expression of TERT in rat GCs. Overexpression of human- TERT enhanced the expression of steroidogenesis genes in gonadotropin-stimulated rat GCs. Moreover, treatment with TERT increasing compounds (AGS) alone enhanced the expression of the steroidogenic genes in both rat and human GCs and in vivo in mouse ovary, while telomerase inhibitor reduced their expression. Treatment with AGS compounds, together with gonadotropin stimulation, additively increased steroidogenic gene expression. Enhancing TERT expression and activity increased the level of progesterone in mouse blood and in the medium of rat GCs and estrogen in women derived pre-ovulatory luteinized GCs. These data suggest that increasing TERT in GCs by pharmaceutical compounds enhanced steroidogenesis and the production of steroid hormones that are essential processes in human and animal reproduction. These data also suggest a novel possible strategy for the enhancement of the production of steroid hormones.

中文翻译：

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端粒酶的增加增强了大鼠和人类颗粒细胞以及小鼠卵巢中类固醇生成基因的表达和类固醇激素的产生。

端粒酶是负责端粒重新伸长的核糖核蛋白，对男性和女性的生育能力很重要。包括类固醇激素雌激素在内的多种因素可调节端粒酶逆转录酶（TERT）的表达，其非典型功能之一是基因表达调控。类固醇生成过程主要受编码类固醇生成酶的基因的转录调控，但不清楚TERT非规范功能是否会影响类固醇生成基因的表达。在这里，我们通过增加大鼠和女性的颗粒细胞（GCs）中的TERT表达和活性来研究这一新概念，这些颗粒细胞来自老鼠和经过体外受精（IVF）程序并在小鼠卵巢中体内的妇女。我们表明，促性腺激素增强了大鼠GC中TERT的表达。人TERT的过表达增强了促性腺激素刺激的大鼠GC中类固醇生成基因的表达。此外，单独使用TERT增加化合物（AGS）进行治疗可增强类固醇生成基因在大鼠和人GC中的表达以及在小鼠卵巢中的体内表达，而端粒酶抑制剂可降低其表达。用AGS化合物处理，加上促性腺激素刺激，可增加类固醇生成基因的表达。增强妇女排卵前黄体化GC的小鼠血液，大鼠GC介质和雌激素中的TERT表达和活性会增加其孕酮水平。这些数据表明，通过药物化合物增加GC中的TERT可以增强类固醇生成和类固醇激素的产生，这是人类和动物繁殖的基本过程。