Title :

Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism

Author(s) :

Fernandois, Daniela [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Rusidze, Mariam [Auteur]
Mueller-Fielitz, Helge [Auteur]
Sauve, Florent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Deligia, Eleonora [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Mauro, Silva [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Evrard, Florence [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Franco-García, Aurelio [Auteur]
Mazur, Daniele [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Martinez Corral, Ines [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Jouy, Nathalie [Auteur]
Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
Rasika, Sowmyalakshmi [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Maurage, Claude-Alain [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Giacobini, Paolo [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Nogueiras, Ruben [Auteur]
Dehouck, Benedicte [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Schwaninger, Markus [Auteur]
Lenfant, Francoise [Auteur]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Journal title :

Metabolism

Abbreviated title :

Metabolism

Volume number :

158

Pages :

155976

Publisher :

Elsevier

Publication date :

2024-07-15

ISSN :

1532-8600

English keyword(s) :

Estrogens
Tanycytes
LH pulsatility
Female metabolism
Reproduction
Hypothalamus

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Estrogen secretion by the ovaries regulates the hypothalamic-pituitary-gonadal axis during the reproductive cycle, influencing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion, and ...
Show more >Background Estrogen secretion by the ovaries regulates the hypothalamic-pituitary-gonadal axis during the reproductive cycle, influencing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion, and also plays a role in regulating metabolism. Here, we establish that hypothalamic tanycytes—specialized glia lining the floor and walls of the third ventricle—integrate estrogenic feedback signals from the gonads and couple reproduction with metabolism by relaying this information to orexigenic neuropeptide Y (NPY) neurons. Methods Using mouse models, including mice floxed for Esr1 (encoding estrogen receptor alpha, ERα) and those with Cre-dependent expression of designer receptors exclusively activated by designer drugs (DREADDs), along with viral-mediated, pharmacological and indirect calorimetric approaches, we evaluated the role of tanycytes and tanycytic estrogen signaling in pulsatile LH secretion, cFos expression in NPY neurons, estrous cyclicity, body-weight changes and metabolic parameters in adult females. Results In ovariectomized mice, chemogenetic activation of tanycytes significantly reduced LH pulsatile release, mimicking the effects of direct NPY neuron activation. In intact mice, tanycytes were crucial for the estrogen-mediated control of GnRH/LH release, with tanycytic ERα activation suppressing fasting-induced NPY neuron activation. Selective knockout of Esr1 in tanycytes altered estrous cyclicity and fertility in female mice and affected estrogen's ability to inhibit refeeding in fasting mice. The absence of ERα signaling in tanycytes increased Npy transcripts and body weight in intact mice and prevented the estrogen-mediated decrease in food intake as well as increase in energy expenditure and fatty acid oxidation in ovariectomized mice. Conclusions Our findings underscore the pivotal role of tanycytes in the neuroendocrine coupling of reproduction and metabolism, with potential implications for its age-related deregulation after menopause. Significance statement Our investigation reveals that tanycytes, specialized glial cells in the brain, are key interpreters of estrogen signals for orexigenic NPY neurons in the hypothalamus. Disrupting tanycytic estrogen receptors not only alters fertility in female mice but also impairs the ability of estrogens to suppress appetite. This work thus sheds light on the critical role played by tanycytes in bridging the hormonal regulation of cyclic reproductive function and appetite/feeding behavior. This understanding may have potential implications for age-related metabolic deregulation after menopause.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

ERC Synergy Grant

ANR Project :

Comment les oestrogènes coordonnent la fertilité et l'homéostasie énergétique dans le systène nerveux central: Dissection des mécanismes moléculaires du récepteur des Oestrogènes ERalpha

Administrative institution(s) :

Université de Lille
CHU Lille
CNRS
Inserm
Institut Pasteur de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41

Research team(s) :

Développement et plasticité du cerveau neuro-endocrine

Submission date :

2024-11-27T22:08:07Z
2024-12-13T14:28:52Z