Neuroendocrinology of Puberty, Fertility and Metabolism

Organization:

Department of Physiology, Institute of Biomedicine, 
University of Turku, Kiinamyllynkatu 10. FI-20520 Turku, Finland

Physiology Section and Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), University of Córdoba
Avda. Menendez Pidal s/n. E-14004 Córdoba, Spain

The Goals of the Projects:

Our research group is interested in deciphering the neuroendocrine and molecular mechanisms responsible for the control of puberty and reproductive function, and how these finely interplay with the systems governing body weight and metabolic homeostasis. In this context, we are actively working in 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, other tachykinins, melanocortins, GnIH) and peripheral (e.g., leptin, sex steroids) regulators, as well as modulation by nutritional and metabolic cues. More recently, our group has become interested in disclosing the role of novel regulatory mechanisms, such as miRNAs, epigenetics and cellular energy sensors, in the joint control of metabolism and reproduction, and how these interplay with central neuropeptide networks (specially kisspeptins). This basic knowledge, generated mostly by the use of at-the-edge preclinical (rodent) models and techniques in neuroendocrine research has set the basis for implementation of translational projects, currently running in our group, targeting the metabolic and reproductive consequences of obesity-induced hypogonadism, as well as improved strategies for the diagnosis and treatment of common reproductive disorders, such as polycystic ovarian syndrome.

Current Topics:

  • To define the roles of miRNAs, cellular energy sensors and epigenetics in the control of key neuronal populations of the reproductive brain, such as Kiss1 neurons
  • To address the roles of Kiss1 neurons, and related neuronal populations, in the control of puberty and fertility, and their modulation by metabolic factors
  • To characterize the mechanisms and impact of hormonal and metabolic alterations linked to obesity, with special attention to obesity-induced hypogonadism
  • To determine the translational value of different neuroendocrine signals and pathways for the improvement of etiopathogenic, diagnostic and therapeutic management of common metabolic and reproductive disorders, such as obesity, infertility and polycystic ovarian syndrome.

Personnel:

This group has been settled in the University of Turku, on the basis of the FiDiPro professorship awarded to Manuel Tena-Sempere in the 2014 Edition of this Program. Within the FiDiPro scheme, one postdoctoral fellow and one predoctoral fellow conduct research activities of this group. Local contacts and collaborations of Tena-Sempere involve mainly the groups of Prof. Matti Poutanen and Prof. Jorma Toppari within CREDE. In addition, Tena-Sempere maintains his activities at his home institution, where he leads a research group at the Biomedical Research Institute of Cordoba (IMIBIC), composed of 18 members, including 3 senior scientists, 6 post-doctoral researchers, 6 predoctoral fellows and 3 technicians.

Recent Publications:

López M, Tena-Sempere M. Estrogens and the control of energy homeostasis: a brain perspective. Trends Endocrinol Metab. 2015; doi: 10.1016/j.tem.2015.06.003

León S, García-Galiano D, Ruiz-Pino F, Barroso A, Manfredi-Lozano M, Romero-Ruiz A, Roa J, Vázquez MJ, Gaytan F, Blomenrohr M, van Duin M, Pinilla L, Tena-Sempere M. Physiological roles of gonadotropin-inhibitory hormone signaling in the control of mammalian reproductive axis: studies in the NPFF1 receptor null mouse. Endocrinology 2014; 155(8):2953-65.

Martínez de Morentin PB, González-García I, Martins L, Lage R, Fernández-Mallo D, Martínez-Sánchez N, Ruíz-Pino F, Liu J, Morgan DA, Pinilla L, Gallego R, Saha AK, Kalsbeek A, Fliers E, Bisschop PH, Diéguez C, Nogueiras R, Rahmouni K, Tena-Sempere M, López M. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metabolism 2014; 20(1):41-53.

Sánchez-Garrido MA, Ruiz-Pino F, Manfredi-Lozano M, Leon S, Garcia-Galiano D, Castaño JP, Luque RM, Romero-Ruiz A, Castellano JM, Diéguez C, Pinilla L, Tena-Sempere M. Obesity-induced hypogonadism in the male: premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms. Endocrinology 2014; 155(3):1067-79.

Sangiao-Alvarellos S, Manfredi-Lozano M, Ruiz-Pino F, Navarro VM, Sánchez-Garrido MA, Leon S, Dieguez C, Cordido F, Matagne V, Dissen GA, Ojeda SR, Pinilla L, Tena-Sempere M. Changes in hypothalamic expression of the Lin28/let-7 system and related microRNAs during postnatal maturation and after experimental manipulations of puberty. Endocrinology 2013; 154(2):942-55.

Navarro VM, Ruiz-Pino F, Sánchez-Garrido MA, García-Galiano D, Hobbs SJ, Manfredi-Lozano M, León S, Sangiao-Alvarellos S, Castellano JM, Clifton DK, Pinilla L, Steiner RA, Tena-Sempere M. Role of neurokinin B in the control of female puberty and its modulation by metabolic status. Journal of Neuroscience 2012; 32(7):2388-97.

García-Galiano D, van Ingen Schenau D, Leon S, Krajnc-Franken MA, Manfredi-Lozano M, Romero-Ruiz A, Navarro VM, Gaytan F, van Noort PI, Pinilla L, Blomenröhr M, Tena-Sempere M. Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice. Endocrinology 2012; 153(1):316-28.

Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiological Reviews 2012; 92(3):1235-316.

Navarro VM, Tena-Sempere M. Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility. Nature Reviews Endocrinology 2011; 8(1):40-53.

García-Galiano D, Navarro VM, Roa J, Ruiz-Pino F, Sánchez-Garrido MA, Pineda R, Castellano JM, Romero M, Aguilar E, Gaytán F, Diéguez C, Pinilla L, Tena-Sempere M. The anorexigenic neuropeptide, nesfatin-1, is indispensable for normal puberty onset in the female rat.  Journal of Neuroscience 2010; 30(23): 7783-92.

Principal Investigator:     
Manuel Tena-Sempere, MD, PhD

Department of Physiology
Institute of Biomedicine
University of Turku

E-mail: matese@utu.fi

Physiology Section and Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC)
University of Córdoba

E-mail: fi1tesem@uco.es

 manuel-tena-sempere
 

Translational research in reproductive and metabolic neuroendocrinology: Focus on puberty and reproductive-metabolic interactions