RT Journal Article
T1 Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity.
A1 Leon, Silvia
A1 Barroso, Alexia
A1 Vazquez, Maria J
A1 Garcia-Galiano, David
A1 Manfredi-Lozano, Maria
A1 Ruiz-Pino, Francisco
A1 Heras, Violeta
A1 Romero-Ruiz, Antonio
A1 Roa, Juan
A1 Schutz, Günther
A1 Kirilov, Milen
A1 Gaytan, Francisco
A1 Pinilla, Leonor
A1 Tena-Sempere, Manuel
AB Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs. indirect effects of kisspeptins on GnRH neurons in vivo, we report herein the detailed reproductive/gonadotropic characterization of a Gpr54 null mouse line with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54(-/-)Tg; rescued). Despite preserved fertility, adult rescued mice displayed abnormalities in gonadal microstructure, with signs of precocious ageing in females and elevated LH levels with normal-to-low testosterone secretion in males. Gpr54(-/-)Tg rescued mice showed also altered gonadotropin responses to negative feedback withdrawal, while luteinizing hormone responses to various gonadotropic regulators were variably affected, with partially blunted relative (but not absolute) responses to kisspeptin-10, NMDA and the agonist of tachykinin receptors, NK2R. Our data confirm that direct effects of kisspeptins on GnRH cells are sufficient to attain fertility. Yet, such direct actions appear to be insufficient to completely preserve proper functionality of gonadotropic axis, suggesting a role of kisspeptin signaling outside GnRH cells.
PB Nature Publishing Group
YR 2015
FD 2015-12-08
LK http://hdl.handle.net/10668/9725
UL http://hdl.handle.net/10668/9725
LA en
NO León S, Barroso A, Vázquez MJ, García-Galiano D, Manfredi-Lozano M, Ruiz-Pino F, et al. Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity. Sci Rep. 2016 Jan 12;6:19206
NO This work was supported by grants BFU2011-025021 and BFU2014-57581-P (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program); Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain); and EU research contract DEER FP7-ENV-2007-1. CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto 25 de Salud Carlos III, Ministerio de Sanidad, Spain.
DS RISalud
RD Apr 8, 2025