Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone β-Subunit Promoted Reproductive Functions in Mice

Int J Mol Sci. 2022 Oct 3;23(19):11735. doi: 10.3390/ijms231911735.

Abstract

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-β-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-β-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-β-(37−49) and hFSH-β-(34−49), created by merging hFSH-β-(34−37) and hFSH-β-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 μg/g BW ip of hFSH-β-(37−49) or hFSH-β-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 μg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-β-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-β-(37−49), both in vivo and in vitro. We concluded that hFSH-β-(37−49) and especially hFSH-β-(34−49), have the potential for reproductive modulation.

Keywords: FSH; mice; pharmacological agent; reproductive modulation; synthetic peptide.

MeSH terms

  • Animals
  • Estradiol
  • Female
  • Follicle Stimulating Hormone / metabolism
  • Follicle Stimulating Hormone, Human*
  • Follicle Stimulating Hormone, beta Subunit*
  • Humans
  • Male
  • Mice
  • Peptide Fragments / metabolism
  • Peptides / pharmacology

Substances

  • Follicle Stimulating Hormone, Human
  • Follicle Stimulating Hormone, beta Subunit
  • Peptide Fragments
  • Peptides
  • Estradiol
  • Follicle Stimulating Hormone