In this project, we are actively working on the characterization of the role of different neuropeptide systems in the neurohormonal regulation of puberty onset and fertility, with special attention to the analysis of the functions of kisspeptins and their interactions with other central (e.g., neurokinin B and other tachykinins) and peripheral (e.g., leptin, sex steroids) regulators, as well as their modulation by nutritional and metabolic cues. The work also includes studies to disclose the role of novel regulatory mechanisms, such as miRNAs, epigenetics, and cellular energy sensors, in the joint control of metabolism and reproduction, and to study how these factors interplay with central neuropeptide networks. In parallel, functional genomic analyses are being applied to dissect out the putative contribution of kisspeptins in central (brain centers) and peripheral (i.e., liver, adipose) tissues for the dynamic control of metabolic homeostasis. As models we mostly use preclinical (rodent) models, including genetically modified mouse lines, and techniques, but clinical collaborations are also undertaken, when relevant. The work is aimed to improve our understanding and strategies for the diagnosis and treatment of common metabolic and reproductive disorders, ranging from polycystic ovarian syndrome to obesity-induced hypogonadism.
PIs: Manuel Tena-Sempere, MD, PhD, professor
Members involved
Senior Researchers: Matti Poutanen, PhD, professor; Guillermo Martinez Nieto, PhD
Doctoral candidates: Krisztina Kukoricza, MSc
Selected publications about research
Franssen D, Barroso A, Ruiz-Pino F, Vázquez MJ, García-Galiano D, Castellano JM, Onieva R, Ruiz-Cruz M, Poutanen M, Gaytán F, Diéguez C, Pinilla L, Lopez M, Roa J, Tena-Sempere M. AMP-activated protein kinase (AMPK) signaling in GnRH neurons links energy status and reproduction. Metabolism. 2021 Feb;115:154460.
Roa J, Barroso A, Ruiz-Pino F, Vázquez MJ, Seoane-Collazo P, Martínez-Sanchez N, García-Galiano D, Ilhan T, Pineda R, León S, Manfredi-Lozano M, Heras V, Poutanen M, Castellano JM, Gaytan F, Diéguez C, Pinilla L, López M, Tena-Sempere M. Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10758-E10767.
Velasco I, León S, Barroso A, Ruiz-Pino F, Heras V, Torres E, León M, Ruohonen ST, García-Galiano D, Romero-Ruiz A, Sánchez-Garrido MA, Olhsson C, Castellano JM, Roa J, Poutanen M, Pinilla L, Vázquez MJ, Tena-Sempere M. Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis. Metabolism. 2019 Sep;98:84-94.
Ruohonen ST, Poutanen M, Tena-Sempere M. Role of kisspeptins in the control of the hypothalamic-pituitary-ovarian axis: old dogmas and new challenges. Fertil Steril. 2020 Sep;114(3):465-474.
Santos-Marcos JA, Barroso A, Rangel-Zuñiga OA, Perdices-Lopez C, Haro C, Sanchez-Garrido MA, Molina-Abril H, Ohlsson C, Perez-Martinez P, Poutanen M, Lopez-Miranda J, Perez-Jimenez F, Tena-Sempere M, Camargo A. Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture. Aging (Albany NY). 2020 Oct 27;12(20):19979-20000.