Gonadotropin-releasing hormone signaling: An information theoretic approach

Abstract

Gonadotropin-releasing hormone (GnRH) is a peptide hormone that mediates central control of reproduction, acting via G-protein coupled receptors that are primarily G coupled and mediate GnRH effects on the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. A great deal is known about the GnRH receptor signaling network but GnRH is secreted in short pulses and much less is known about how gonadotropes decode this pulsatile signal. Similarly, single cell measures reveal considerable cell-cell heterogeneity in responses to GnRH but the impact of this variability on signaling is largely unknown. Ordinary differential equation-based mathematical models have been used to explore the decoding of pulse dynamics and information theory-derived statistical measures are increasingly used to address the influence of cell-cell variability on the amount of information transferred by signaling pathways. Here, we describe both approaches for GnRH signaling, with emphasis on novel insights gained from the information theoretic approach and on the fundamental question of why GnRH is secreted in pulses.

Information Processing in Affective Disorders: Did an Ancient Peptide Regulating Intercellular Metabolism Become Co‐Opted for Noxious Stress Sensing?

“…These studies however, along with advances in neural information theory, underscored the importance of interneuronal communication in the brain and confirmed, in part, that no specific region of the brain was entirely responsible for the behavioral manifestations of mood disorders. [ 6–10 ] Instead, a subset of several active brain nuclei appeared to be required where the loci could vary among patients. As a result, methods that employed whole brain activity via imaging studies such as functional positronic emission tomography (fPET), nuclear magnetic resonance spectrometry and indeed, re‐visitation of electroencephalography led to the confirmation that numerous regions rather than a single locus of the brain were associated with the onset of affective disorders.…”

Anti-Metastatic Effect of GV1001 on Prostate Cancer Cells; Roles of GnRHR-Mediated Gαs-cAMP Pathway and AR-YAP1 Axis

“…Ligand-stimulated GnRHR triggers multiple signaling pathways through diverse Gα proteins. Among the G protein pathways, the activated Gαq mediates reproductive function in pituitary cells and is considered as the primary pathway for GnRHR (7)(8)(9). It has been also reported that GnRH analogs possess inhibitory effects in several cancer cell types via Gαi protein.…”

“…As one of the GPCR families, GnRHR transduces the intracellular GPCR signals via multiple heterotrimeric G proteins (5,6). In pituitary gonadotropes, GnRHR primarily interacts with Gαq and exerts reproductive effects such as synthesis and secretion of pituitary gonadotropin hormones, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (7)(8)(9).…”

Mathematical modeling approaches of cellular endocrinology within the hypothalamo-pituitary-gonadal axis

“…Finally, an original approach tackled the question from a signal engineering viewpoint, applying the concepts of information transfer (Voliotis et al, 2018). The main interest is to take advantage of the information processing properties resulting from the heterogeneity of responses within a cell population.…”