Françoise LENFANT / CORALIE FONTAINE

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 dialogue between estrogenic and circadian signaling, 4) develop 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

Mélissa BUSCATO

Silveric GILARDI

Chanaëlle FEBRISSY

Adrien GARGAROS

Mariam RUSIDZE
IMPACT OF AGING ON ARTERIAL PROTECTION BY ESTROGENS

Coordinators : Coralie Fontaine, Jean-François Arnal
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. This project is conducted in partnership with the company Physiotim (Castres, France).
OPTIMIZATION OF ESTROGEN RECEPTOR MODULATION

Coordinators : Coralie Fontaine, Marine Adlanmerini, Marie-Cécile Valéra, 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 to optimize hormonal therapies used in various pathologies in women (treatment of menopausal symptoms, breast cancer, endometriosis?). We are contributing to these developments through partnerships with a Belgian Biotech (Mithra) which is developing estetrol, a fetal estrogen and big pharmas (Pfizer).
DIALOGUE BETWEEN ESTROGENIC AND CIRCADIAN SIGNALING

Coordinators : Marine Adlanmerini, Coralie Fontaine
Estrogen receptor alpha (ERa), the major mammalian estrogen receptor, is expressed with a large circadian rhythm. Furthermore, estrogen signaling is known to regulate several circadian functions in women, but also in men. By exploring the hypothesis that ERα may act as a time donor capable of driving circadian metabolism, our team aims to determine the molecular mechanisms and physio(patho)logical implications of the dialogue between estrogen and circadian signaling.
THE MECHANISM OF ACTION OF OESTROGENS IN ENDOMETRIOSIS

Coordinators : Elodie Chantalat, 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. Our project proposes a multidisciplinary approach to better understand ERα mechanisms of actions in endometriosis, using tissue biopsies and developing a platform of organoids derived from these tissues. The ultimate goal is to propose new therapeutics to control the endometriotic process without inducing systemic estrogen deprivation and its long-term deleterious consequences. Financial support from EndoFrance association and the Occitanie-Pyrénées Region (GRAINE- EndoTREAT in partnership with CHU and Urosphere).
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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