Françoise LENFANT/Pierre GOURDY

MODULATION OF THE OESTROGEN RECEPTOR ERα: VASCULAR, METABOLIC and ENDOCRINE DYSFUNCTIONS (ESTER)
Our work is focused on understanding the molecular and cellular mechanisms of actions of Estrogen Receptor ERα in its physiological vasculoprotective and metabolic preventive effects of estrogens and Selective Estrogen Receptors Modulators (SERMs). Four main axes are developed, in collaboration with clinicians at the CHU of Toulouse: 1) prevent apparition of aging-vascular diseases, 2) contribute to the development of new estrogenic molecules to improve the safety of oral contraception and of menopausal hormone therapy, 3) understand some mechanisms of sex dimorphism in incidence of cardiovascular and metabolic disorders, 4) develop a translational research on an estrogenic dependent pathology: endometriosis.
10th French Nuclear Receptors Meeting: May 19-20TH 2022

Since 2011, the French Nuclear Receptor Days have brought together the French scientific community working in the field of nuclear receptors. Following the observation that our paths cross only during international congresses, these French Nuclear Receptors Days are organized on an annual basis to increase our interactions and promote collaborations. The meeting is usually organized over a day and a half, each year in a different city to allow as many people as possible to participate.
The philosophy is that one or two renowned scientists speak in a plenary conference. Then, only students and post-doctoral fellows present their results in a 15-minute format followed by questions, all in English for the sake of training and accessibility to an audience where foreigners working in our laboratories are present.
The objective of this conference is threefold: train young scientists in scientific communications, disseminate recent scientific and technological knowledge, and promote the emergence of collaborations at national and international levels, since members of European laboratories can also join this scientific meeting.
After an interruption related to the COVID-19 health crisis, Toulouse is pleased to welcome the French Nuclear Receptor meeting for its 10th anniversary. The topics covered will be:
- Nuclear receptors in physiopathology
- Structure and mechanisms of action of nuclear receptors
- Nuclear receptors in development and cancers
Important note:
- The sanitary pass is mandatory to attend the meeting
- The meeting could be changed to a remote-only event according to the COVID situation
TEAM

Françoise LENFANT

Pierre GOURDY

Marine ADLANMERINI

Jean-François ARNAL

Coralie FONTAINE

Alexandra MONTAGNER

Elodie CHANTELAT

Xavier GAME

Emmanuelle NOIRRIT-ESCLASSANC

Florence TREMOLIERES

Marie VALERA

Alexia VINEL

Mélissa BUSCATO

Adrien GARGAROS

Silveric GILARDI

Morgane DAVEZAC

Chanaëlle FEBRISSY

Mariam RUSIDZE

Blandine TRAMUNT

Ana Gracia ALVAREZ TENA

Aurélie BUFFETEAU
IMPACT OF AGING ON ARTERIAL PROTECTION BY ESTROGENS

Coordinators : Coralie Fontaine, Marie-Cécile Valéra, Jean-François Arnal et Françoise Lenfant
Women are protected against cardiovascular risk compared to men until menopause. This protection conferred by endogenous estrogens during the period of genital activity can be extended with estrogen supplementation when hormonal treatment is administered early after the onset of menopause. Our goal is to understand the loss of arterial protection by estrogens during aging by studying the impact of age on the signaling of Estrogen receptor ERα signaling in arterial wall.
IMPROVEMENT OF HORMONAL TREATMENT OF THE MENOPAUSE

Coordinators : Coralie Fontaine, Marine Adlanmerini, Alexia Vinel, Emmanuelle Noirrit, Florence Tremolières, Jean-François Arnal et Françoise Lenfant
Using a combination of pharmacological approaches and the use of mouse models targeting the different sub-functions of ERα (nuclear versus membrane-initiated signaling), our objectives are to optimize the activation of ERα to develop new therapeutic strategies for the revival of menopause treatment and the prevention of age-related vascular and metabolic diseases while limiting its deleterious impact on hepatic coagulation factors and on the development of breast and endometrial cancer. We are contributing to these developments through partnerships with a Belgian Biotech (Mithra) which is developing estetrol, a fetal estrogen and big pharmas (Pfizer).
GENDER DIFFERENCES IN METABOLIC DISEASES (OBESITY/DIABETES/NASH)

Coordinators : Alexandra Montagner, Pierre Gourdy, Marine Adlanmerini, et Françoise Lenfant
Estrogens are key regulators of energy homeostasis and glucose homeostasis. Among tissue targets of estrogens involved in such actions, the central nervous system (CNS) and the liver are known to play prominent roles in sex dimorphic protection from metabolic disorders. Exploring the hypothesis that ERα could act as a nutritional modulator that guarantees optimal metabolic flexibility, our team thus aims at providing new insights into ERα-mediated mechanisms contributing to CNS and liver adaptation to various nutritional status.
THE MECHANISM OF ACTION OF OESTROGENS IN ENDOMETRIOSIS

Coordinators : Elodie Chantalat, Xavier Gamet, Marie-Cécile Valera, Françoise Lenfant
Endometriosis, present in 10% of reproductive-aged women, is an estrogen-dependent, chronic inflammatory gynecologic disease that is characterized by the presence of endometrial tissue outside the uterus and induced pelvic pain, infertility and impaired quality of life. In this context, our main objective is to develop new set of relevant models of endometriotic lesions and investigate ERα mechanisms to further propose to control the endometriotic process without inducing systemic estrogen deprivation and its deleterious long-term consequences.
RECENT PUBLICATIONS
Tamoxifen Accelerates Endothelial Healing by Targeting ERα in Smooth Muscle Cells, Zahreddine R, Davezac M, Smirnova N, Buscato M, Lhuillier E, Lupieri A, Solinhac R, Vinel A, Vessieres E, Henrion D, Renault MA, Gadeau AP, Flouriot G, Lenfant F, Laffargue M, Métivier R, Arnal JF, Fontaine C.,Circ Res, 2020. Pubmed
Mutation of Arginine 264 on ERα (Estrogen Receptor Alpha) Selectively Abrogates the Rapid Signaling of Estradiol in the Endothelium Without Altering Fertility, Adlanmerini M, Fébrissy C, Zahreddine R, Vessières E, Buscato M, Solinhac R, Favre J, Anquetil T, Guihot AL, Boudou F, Raymond-Letron I, Chambon P, Gourdy P, Ohlsson C, Laurell H, Fontaine C, Metivier R, Le Romancer M, Henrion D, Arnal JF, Lenfant F, Arterioscler Thromb Vasc Biol, 2020.Pubmed
Sex differences in metabolic regulation and diabetes susceptibility, Tramunt B, Smati S, Grandgeorge N, Lenfant F, Arnal JF, Montagner A, Gourdy P, Diabetologia, 2020. Pubmed
Membrane expression of the estrogen receptor ERα is required for intercellular communications in the mammary epithelium, Gagniac L, Rusidzé M, Boudou F, Cagnet S, Adlanmerini M, Jeannot P, Gaide N, Giton F, Besson A, Weyl A, Gourdy P, Raymond-Letron I, Arnal JF, Brisken C, Lenfant F, Development, 2020. Pubmed
Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications, Arnal JF, Lenfant F, Metivier R, Flouriot G, Henrion D, Adlanmerini M, Fontaine C, Gourdy P, Chambon P, Katzenellenbogen B, Katzenellenbogen J, Physiol Rev, 2017. Pubmed


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