GnRH-driven FSH synthesis and secretion are modulated through circ-ptpn4 ceRNA sequestration of let-7b-5p miRNA, which negatively controls ELK1 expression

  • Theriogenology. 2026 Mar 1:252:117721. doi: 10.1016/j.theriogenology.2025.117721.
Yu-Xin Zhang  1 ,  Ling-Ling Qiu  2 ,  Zhe Zhang  3 ,  Hai-Xiang Guo  4 ,  Yi Zheng  5 ,  Bing-Bing Wang  6 ,  Cheng-Zhen Chen  7 ,  Hao Jiang  8 ,  Jia-Bao Zhang  9 ,  Fei Gao  10 ,  Bao Yuan  11
Affiliations
  • 1. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 2. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 3. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 4. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 5. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 6. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 7. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 8. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 9. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 10. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
  • 11. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, 130062, Jilin, PR China. Electronic address: [email protected].
PMID: 41289789 DOI: 10.1016/j.theriogenology.2025.117721
Abstract

During animal growth and development, the reproductive system is tightly controlled by the central nervous system through a highly conserved, self-feedback loop-the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH), which is produced in the hypothalamus and secreted into the hypophyseal portal circulation, serves as a master regulator of pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion, thereby orchestrating growth and reproductive functions. We identified circ-ptpn4 as a GnRH-responsive circular RNA (circRNA) that sequesters let-7b-5p, thereby attenuating its suppression of ELK1. This decrease in let-7b-5p availability thus allows enhanced ELK1 expression, which ultimately stimulates FSH production. In summary, we revealed a novel competing endogenous RNA (ceRNA)-dependent pathway (circ-ptpn4/let-7b-5p/ELK1) underlying GnRH-induced FSH regulation.

Keywords
FSH; GnRH; Pituitary; ceRNA; microRNA.
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