Reactive Oxygen Species Link Gonadotropin-Releasing Hormone Receptor Signaling Cascades in the Gonadotrope

Abstract

Biological rhythms lie at the center of regulatory schemes that control many aspects of living systems. At the cellular level, meaningful responses to external stimuli depend on propagation and quenching of a signal to maintain vigilance for subsequent stimulation or changes that serve to shape and modulate the response. The hypothalamus–pituitary–gonad endocrine axis that controls reproductive development and function relies on control through rhythmic stimulation. Central to this axis is the pulsatile stimulation of the gonadotropes by hypothalamic neurons through episodic release of the neuropeptide gonadotropin-releasing hormone. Alterations in pulsatile stimulation of the gonadotropes result in differential synthesis and secretion of the gonadotropins LH and FSH and changes in the expression of their respective hormone subunit genes. The requirement to amplify signals arising from activation of the gonadotropin-releasing hormone (GnRH) receptor and to rapidly quench the resultant signal to preserve an adaptive response suggests the need for rapid activation and feedback control operating at the level of intracellular signaling. Emerging data suggest that reactive oxygen species (ROS) can fulfill this role in the GnRH receptor signaling through activation of MAP kinase signaling cascades, control of negative feedback, and participation in the secretory process. Results obtained in gonadotrope cell lines or other cell models indicate that ROS can participate in each of these regulatory cascades. We discuss the potential advantage of reactive oxygen signaling for modulating the gonadotrope response to GnRH stimulation and the potential mechanisms for this action. These observations suggest further targets of study for regulation in the gonadotrope.

Assessment of follicular fluid paraoxonase activity with pregnancy outcomes in women undergoing IVF/ICSI

“…Besides, the potential advantage of evaluating PON-1 as a biomarker in the clinical diagnosis or treatment of oxidative stress was proposed [35]. Valkenburg et al, (2008) found in their study increased OS in PCOS women, which agreed with our result where the antioxidant PON1 activity was higher in the PCOS group to rebalance the higher OS [28], which may affect characteristics of embryos that correlate adversely with OS [36]. Proteomic analysis of follicular fluid documented 31 up-regulated proteins and 18 down-regulated proteins with different functions, only 5 of which have a function in the genital system.…”

Oxidative stress and DNA damage status in couples undergoing in vitro fertilization treatment

“…ROS generated by alcohol, smoking, or environmental factors might affect FSH synthesis (Zubair et al, 2017, Oremosu and Akang, 2015, Aprioku and Ugwu, 2016. Research has shown that ROS affects FSH's secretion via its effect on the gonadotropinreleasing hormone (Terasaka et al, 2017). This mechanism could not be corroborated in the present study.…”

GLUT1-mediated glycolysis supports GnRH-induced secretion of luteinizing hormone from female gonadotropes

“…In vivo, GnRH is pulsatile and elicits pulsatile secretion of LH 20 . A hallmark of gonadotropes is their ability to resolve signaling input from a GnRH pulse and reset for subsequent stimulation by a following pulse of GnRH 30 , 31 . Therefore, we examined whether GnRH-induced glycolysis is pulsatile with GnRH.…”