Hypothalamic regulatory mechanisms of reproduction
Gonadotropin-releasing hormone (GnRH)-synthesizing neurons represent the final output pathway of the hypothalamus in the neuroendocrine control of reproduction. Pulsatile GnRH secretion into the hypophysial portal circulation regulates the synthesis and release of the two pituitary gonadotropins, LH and FSH, which in turn, govern gonadal functions. Gonadal sex steroid hormones exert positive and negative feedback effects on the neurosecretory output of GnRH neurons via mechanisms that are poorly understood. A major research focus of the Laboratory of Endocrine Neurobiology has been on the neuronal and hormonal mechanisms that regulate GnRH neuronal functions.
· The Laboratory has provided the first neuromorphological evidence for the presence of the beta isoform of the estrogen receptor (ER-β) in GnRH neurons of rats and humans that lack the classic estrogen receptor (ER-α).
· A recently revealed feature of GnRH neurons their glutamatergic character, based on the expression of vesicular glutamate transporter-2 (vGLUT-2) mRNA and protein, has also been reported first from the Laboratory.
· Regarding the networking of GnRH neurons, we have provided structural and functional evidence for receiving neuronal inputs from kisspeptin, ghrelin, secretin, glucagon-like peptide 1, vasopressin, galanin, GABA, glutamate-synthesizing loci of the brain.
· We have discovered that endocannabinoid and nitric oxide retrograde signaling mechanisms regulate the presynaptic terminals of GnRH neurons and confirmed their participation in the execution of the direct, negative, and positive estradiol feedback actions.
· We have also contributed to elucidation of the transcriptome of GnRH neurons reporting a marked sexual dimorphism in mice and a gonadal cycle-dependent expression.
C. Vastagh, V. Csillag, N. Solymosi, I. Farkas, and Z. Liposits, “Gonadal Cycle-Dependent Expression of Genes Encoding Peptide-, Growth Factor-, and Orphan G-Protein-Coupled Receptors in Gonadotropin- Releasing Hormone Neurons of Mice,” FRONTIERS IN MOLECULAR NEUROSCIENCE, vol. 13, 2021.
C. Vastagh, I. Farkas, M. M. Scott, and Z. Liposits, “Networking of glucagon-like peptide-1 axons with GnRH neurons in the basal forebrain of male mice revealed by 3DISCO-based immunocytochemistry and optogenetics.,” BRAIN STRUCTURE & FUNCTION, vol. 226, no. 1, pp. 105–120, 2021.
V. Csillag, C. Vastagh, Z. Liposits, and I. Farkas, “Secretin Regulates Excitatory GABAergic Neurotransmission to GnRH Neurons via Retrograde NO Signaling Pathway in Mice.,” FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 13, 2019.
C. Vastagh, N. Solymosi, I. Farkas, and Z. Liposits, “Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice,” FRONTIERS IN MOLECULAR NEUROSCIENCE, vol. 12, 2019.
I. Farkas, F. Bálint, E. Farkas, C. Vastagh, C. Fekete, and Z. Liposits, “Estradiol Increases Glutamate and GABA Neurotransmission into GnRH Neurons via Retrograde NO-Signaling in Proestrous Mice during the Positive Estradiol Feedback Period,” ENEURO, vol. 5, no. 4, 2018.
I. Farkas, C. Vastagh, E. Farkas, F. Balint, K. Skrapits, E. Hrabovszky, C. Fekete, and Z. Liposits, “Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways.,” FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 10, no. SEP2016, p. 214, 2016.
F. Balint, Z. Liposits, and I. Farkas, “Estrogen Receptor Beta and 2-arachidonoylglycerol Mediate the Suppressive Effects of Estradiol on Frequency of Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons of Metestrous Mice: An Acute Slice Electrophysiological Study.,” FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 10, p. 77, 2016.
C. Vastagh, A. Rodolosse, N. Solymosi, I. Farkas, H. Auer, M. Sarvari, and Z. Liposits, “Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice.,” NEUROENDOCRINOLOGY, vol. 102, no. 1–2, pp. 44–59, 2015.
I. Farkas, V. Csaba, S. Miklós, and L. Zsolt, “Ghrelin Decreases Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons in an Estrous Cycle and Endocannabinoid Signaling Dependent Manner.,” PLOS ONE, vol. 8, no. 10, p. e78178, 2013.
I. Kallo, B. Vida, L. Deli, C. Molnar, E. Hrabovszky, A. Caraty, P. Ciofi, C. Coen, and Z. Liposits, “Co-localisation of kisspeptin with galanin or neurokinin B in afferents to mouse GnRH neurones,” JOURNAL OF NEUROENDOCRINOLOGY, vol. 24, no. 3, pp. 464–476, 2012.