Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, 430070, China.
Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Veterans Affairs Nebraska Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE, 68105, USA.
Mol Cell Endocrinol. 2020 Aug 20;514:110911. doi: 10.1016/j.mce.2020.110911. Epub 2020 Jun 15.
Previous studies have reported hypo-glycosylated FSH and fully-glycosylated FSH to be naturally occurring in humans, and these glycoforms exist in changing ratios over a woman's lifespan. The precise cellular and molecular effects of recombinant human FSH (hFSH) glycoforms, FSH21 and FSH24, have not been documented in primary granulosa cells. Herein, biological responses to FSH21 and FSH24 were compared in primary porcine granulosa cells. Hypo-glycosylated hFSH21 was significantly more effective than fully-glycosylated hFSH24 at stimulating cAMP accumulation and protein kinase A (PKA) activity, leading to the higher phosphorylation of CREB and β-Catenin. Compared to fully-glycosylated hFSH24, hypo-glycosylated hFSH21 also induced greater levels of transcripts for HSD3B, STAR and INHA, and higher progesterone production. Our results demonstrate that hypo-glycosylated hFSH21 exerts more robust activation of intracellular signals associated with steroidogenesis than fully-glycosylated hFSH24 in primary porcine granulosa cells, and furthers our understanding of the differing bioactivities of FSH glycoforms in the ovary.
先前的研究报告称，人类体内天然存在低糖化 FSH 和全糖化 FSH，这些糖型在女性的生命周期中以不断变化的比例存在。重组人促卵泡激素（hFSH）糖型 FSH21 和 FSH24 的具体细胞和分子作用尚未在原始颗粒细胞中记录。在此，比较了 FSH21 和 FSH24 在原代猪颗粒细胞中的生物学反应。低糖化 hFSH21 比全糖化 hFSH24 更有效地刺激 cAMP 积累和蛋白激酶 A（PKA）活性，导致 CREB 和 β-连环蛋白的更高磷酸化。与全糖化 hFSH24 相比，低糖化 hFSH21 还诱导更高水平的 HSD3B、STAR 和 INHA 的转录物，并产生更高水平的孕激素。我们的研究结果表明，低糖化 hFSH21 在原代猪颗粒细胞中比全糖化 hFSH24 更能强烈激活与甾体生成相关的细胞内信号，进一步了解了 FSH 糖型在卵巢中的不同生物活性。
