1. Academic Validation
  2. Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators

Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators

  • Syst Biol Reprod Med. 2022 Apr;68(2):138-150. doi: 10.1080/19396368.2021.2003910.
Jingyuan Xiong 1 Ye Tian 1 Aru Ling 2 Zhenmi Liu 1 Li Zhao 1 Guo Cheng 2
Affiliations

Affiliations

  • 1 Healthy Food Evaluation Research Center, Department of Occupational and Environmental Health, Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • 2 Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Abstract

Epidemiological studies have shown that genistein, an isoflavonoid phytoestrogen from soybean, affects endocrine and reproductive systems and alters pubertal onset. Administration of genistein in mice could impact the electrophysiology of hypothalamic neurons associated with the secretion of gonadotropin-releasing hormone (GnRH), a key component of hypothalamic-pituitary-gonadal (HPG) axis that governs hormone release and reproductive maturation. However, whether genistein could directly influence GnRH secretion in GnRH-specific neurons requires further investigation. Here, mouse hypothalamic GT1-7 neurons were recruited as a GnRH-expressing model to directly evaluate the effect and mechanisms of genistein on GnRH release. Results from this study demonstrated that genistein treatment decreased cell viability, impacted cell cycle distribution, and induced Apoptosis of GT1-7 cells. A high concentration of genistein (20 μM) significantly increased GnRH secretion by 122.4% compared to the control. Since GnRH release is regulated by components of the kisspeptin-neurokinin-dynorphin (KNDy) system and regulators including SIRT1, PKCγ, and MKRN3, their transcription and translation were examined. Significant increases were observed for the mRNA and protein levels of the KNDy component Kisspeptin Receptor (Gpr54/Kissr). Compared to the control, genistein treatment upregulated the level of SIRT1 mRNA level, while it downregulated Prkcg and Mkrn3 expression. Therefore, this study provided direct evidence that genistein treatment could affect GnRH secretion by modulating kisspeptin receptors, SIRT1, PKCγ and MKRN3 in GT1-7 cells.Abbreviations: GnRH: gonadotropin-releasing hormone; HPG: hypothalamic-pituitary-gonadal; KNDy: kisspeptin-neurokinin-dynorphin; LH: luteinizing hormone; FSH: follicle-stimulating hormone; ARC: arcuate nucleus; ER: estrogen receptor; SIRT1: silent information regulator 1; PKCγ: protein kinase c γ: MKRN3: makorin ring finger protein 3; LC: lethal concentration; PI: propidium iodide; ECL: chemiluminescence; BCA: bicinchoninic acid assay; PBS: phosphate-buffered saline; CT: fluorescence reached threshold; PVDF: polyvinylidene difluoride.

Keywords

GT1-7 cells; GnRH; KNDy components; genistein; isoflavone; phytoestrogen.

Figures
Products
Inhibitors & Agonists
Other Products