2. Academic Validation
  3. Neurokinin 3 receptor agonist senktide stimulates GnRH release in isolated hypogonadotropic hypogonadism mice

Neurokinin 3 receptor agonist senktide stimulates GnRH release in isolated hypogonadotropic hypogonadism mice

  • FASEB J. 2025 Mar 31;39(6):e70498. doi: 10.1096/fj.202403365R.
Menglong Xiong 1,  Yuting Li 1,  Shan Tan 1,  Chunlin Yang 2,  Lin Liu 1,  Zhiheng Chen 1
Affiliations

Affiliations

  • 1 Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.
  • 2 School of Medicine, The University of Missouri, Columbia, Missouri, USA.
PMID: 40135619 DOI: 10.1096/fj.202403365R
Abstract

Isolated hypogonadotropic hypogonadism (IHH) is caused by defective gonadotropin-releasing hormone (GnRH) secretion or action, resulting in absent or incomplete pubertal development and infertility. However, the pathogenesis mechanism of IHH is not fully understood. This study utilized PROK2/PROKR2 knockdown mice and GT1-7 cells to investigate the effects and potential mechanismsof the NK3R Agonist senktide on GnRH deficiency and related syndromes. In this investigation, PROK2/PROKR2 knockdown resulted in a deficiency of GnRH neurons, reduced levels of LSH, FSH, and E2, and the inhibition of the MAPK/ERK and PI3K/Akt pathways in mice. However, this effect was reversed by senktide. Furthermore, the inhibition of MAPK/ERK or PI3K/Akt signaling pathways counteracted the remission of the GnRH insufficiency and associated syndrome by senktide in mice with PROK2/PROKR2 knockdown. In summary, NK3R Agonist senktide alleviated the GnRH insufficiency and related syndromes caused by PROK2/PROKR2 knockdown via the MAPK/ERK pathway and the PI3K/Akt pathway.

Keywords

GPCR; IHH; NK3R; prokineticin; prokineticin receptors; senktide.

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