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.
Les travaux de Jean-François Arnal et Françoise Lenfant sont sélectionnés pour le Prix Galien 2022

JF. Arnal and F. Lenfant have been included in the Official Selection of the Prix Galien 2022 in the “Research work” section.
Their work is honoured: the coronary artery risk of women is reduced by oestrogen hormones, but at the cost of certain risks. By better understanding their mechanisms of action, the work of Jean-François Arnal and Françoise Lenfant proposes a safer modulation of the estrogen receptor in medicine (contraception, menopause).
TEAM

Françoise LENFANT

Coralie FONTAINE

Jean-François ARNAL

Marine ADLANMERINI

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

Ana Gracia ALVAREZ TENA

Christelle ALLIOT
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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