Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China.
Faculty of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China.
Gene. 2022 Mar 10;814:146128. doi: 10.1016/j.gene.2021.146128. Epub 2021 Dec 29.
Melatonin, an important regulator of mammalian reproduction, is mainly produced in the pineal gland, and granulosa cells (GCs), the main mammalian ovarian secretory cells, synthesize melatonin and express melatonin receptors (MRs) MT1 and MT2. However, studies on melatonin regulation in GCs are lacking in sheep. In this study, we explored the effects of β-estradiol (E2) on melatonin production and MR expression in GCs. We cultured sheep GCs to analyze the expression of the melatonin rate-limiting enzymes AANAT and HIOMT and the effects of E2 on AANAT, HIOMT, and MR expression and melatonin synthesis. To determine whether estrogen receptors (ERs) mediated E2 action on melatonin secretion and MR expression, we assessed ERA and ERB expression in GCs and observed whether ER antagonists counterbalanced the effects of E2. GCs expressed AANAT and HIOMT mRNA, indicating that they transformed exogenous serotonin into melatonin. E2 inhibited melatonin production by downregulating AANAT, HIOMT, and MRs. GCs expressed ERA and ERB; ERA/ERB inhibitors abolished E2-mediated inhibition of melatonin secretion and MR expression. PHTPP upregulated melatonin secretion and MT1 expression in E2-treated GCs, but did not significantly affect AANAT and MT2 expression. In conclusion, melatonin secretion in GCs was inhibited by E2 through an ERA- and ERB-mediated process.
褪黑素是哺乳动物生殖的重要调节剂，主要由松果体产生，而颗粒细胞（GCs）是哺乳动物主要的卵巢分泌细胞，可合成褪黑素并表达褪黑素受体（MRs）MT1 和 MT2。然而，关于褪黑素在绵羊 GCs 中的调节作用的研究还很少。在这项研究中，我们探讨了β-雌二醇（E2）对 GCs 中褪黑素产生和 MR 表达的影响。我们培养绵羊 GCs 以分析褪黑素限速酶 AANAT 和 HIOMT 的表达，以及 E2 对 AANAT、HIOMT 和 MR 表达和褪黑素合成的影响。为了确定雌激素受体（ERs）是否介导 E2 对褪黑素分泌和 MR 表达的作用，我们评估了 GCs 中 ERA 和 ERB 的表达，并观察了 ER 拮抗剂是否抵消了 E2 的作用。GCs 表达 AANAT 和 HIOMT mRNA，表明它们将外源性 5-羟色胺转化为褪黑素。E2 通过下调 AANAT、HIOMT 和 MRs 抑制褪黑素的产生。GCs 表达 ERA 和 ERB；ERA/ERB 抑制剂消除了 E2 介导的对褪黑素分泌和 MR 表达的抑制作用。PHTPP 上调了 E2 处理的 GCs 中的褪黑素分泌和 MT1 表达，但对 AANAT 和 MT2 表达没有显著影响。总之，E2 通过 ERA 和 ERB 介导的过程抑制 GCs 中的褪黑素分泌。
