GnRH-I is a neuropeptide capable of regulating the release of gonadotropins, used to modulate the physiological functions of the reproductive system[1]. GnRH-I stimulates the anterior pituitary to release gonadotropins, thereby regulating the synthesis and secretion of gonadal hormones and maintaining reproductive endocrine balance[2]. GnRH-I can be used to study the regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis and its role in reproductive-related diseases[3]. GnRH-I may also play a significant role in the growth of ovarian tumors[4].
In vitro, GnRH-I (3nM) stimulation of gonadotropin cells from neonatal rat pituitary for 3 hours significantly promotes the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process depends on the activation of intracellular calcium signaling and cyclic nucleotide signaling pathways[5]. Treatment of human extravillous cytotrophoblasts (EVTs) with GnRH-I (0.1–100nM) for 24 hours significantly upregulates the mRNA and protein expression levels of urokinase-type plasminogen activator (uPA), while downregulating the expression of plasminogen activator inhibitor-1 (PAI-1). This enhances extracellular matrix degradation capacity, thereby promoting the invasive potential of trophoblast cells during early pregnancy[6].
In vivo, a single intravenous bolus of GnRH-I (0.01–10μg/kg body weight) administered to female rhesus monkeys aged 8–12 months and 21–23 months significantly promotes the release of plasma luteinizing hormone (LH), with younger individuals showing greater sensitivity[7].
References:
[1] Cheng CK, Leung PC. Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr Rev. 2005 Apr;26(2):283-306.
[2] Leung PC, Cheng CK, Zhu XM. Multi-factorial role of GnRH-I and GnRH-II in the human ovary. Mol Cell Endocrinol. 2003 Apr 28;202(1-2):145-53.
[3] Kern J, Schilling D, Schneeweis C, et al. Identification of the unfolded protein response pathway as target for radiosensitization in pancreatic cancer. Radiother Oncol. 2024 Feb;191:110059.
[4] Kang SK, Choi KC, Yang HS, et al. Potential role of gonadotrophin-releasing hormone (GnRH)-I and GnRH-II in the ovary and ovarian cancer. Endocr Relat Cancer. 2003 Jun;10(2):169-77.
[5] Balík A, Jindřichová M, Bhattacharyya S, et al. GnRH-I and GnRH-II-induced calcium signaling and hormone secretion in neonatal rat gonadotrophs. Physiol Res. 2009;58(5):709-716.
[6] Chou CS, Zhu H, Shalev E, et al. The effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro. J Clin Endocrinol Metab. 2002 Dec;87(12):5594-603.
[7] Densmore VS, Urbanski HF. Relative effect of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on gonadotropin release. J Clin Endocrinol Metab. 2003 May;88(5):2126-34.