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.

TEAM

Tous / AllTeam leaderResearchersCliniciansTechnical staffStudents
Team leader

Françoise LENFANT

Team leader

Pierre GOURDY

Marine ADLANMERINI
Researcher

Marine ADLANMERINI

Reseachers

Jean-François ARNAL

Researcher

Coralie FONTAINE

Researcher

Alexandra MONTAGNER

Elodie CHANTELAT
CLINICIAN

Elodie CHANTELAT

Xavier GAME
CLINICIAN

Xavier GAME

CLINICIAN

Emmanuelle NOIRRIT-ESCLASSANC

CLINICIAN

Florence TREMOLIERES

CLINICIAN

Marie VALERA

CLINICIAN

Alexia VINEL

Engineer

Mélissa BUSCATO

Engineer

Adrien GARGAROS

Engineer

Silveric GILARDI

PhD Student

Morgane DAVEZAC

PhD Student

Chanaëlle FEBRISSY

PhD Student

Mariam RUSIDZE

PhD Student

Blandine TRAMUNT

Student

Ana Gracia ALVAREZ TENA

Student

Aurélie BUFFETEAU

Team leader

Françoise LENFANT

PhD, Director of research, Group leader

Career path

Françoise LENFANT received her PhD in Microbiology from the Institut National des Sciences Appliqués à Toulouse, in 1991. From 1991 to 1994, she worked as a post-doctoral fellow in the field of Molecular Biology at the University of California, USA, then in Toulouse in the field of reproduction and was recruited as a principal investigator at INSERM, Toulouse, in 1997. Since 2005, Francoise LENFANT is a Director of research at the INSERM U1297, working on modulation of Estrogen Receptor in medicine.

Main domains of expertise

Sexual steroids, Estrogen Receptor, reproduction, endothelium, breast cancer, in vivo models.

Team leader

Pierre GOURDY

Professor in Endocrinology, Diabetes & Metabolic Diseases

Career path

Graduated in 1997 (MD) and 2004 (PhD), Pierre Gourdy was promoted in 2005 to Professor in Endocrinology, Diabetes and Metabolic Diseases at Toulouse 3 University and Toulouse University Hospital. Since 2016, he leads the University Federation IMPACT (Innovative Medicine for the Prevention and treatment of Cardiovascular and metabolic diseases) which federates 10 clinical teams and 4 research institutes to promote research efforts in the field of metabolic and cardiovascular diseases.

Main domains of expertise

Diabetes, non-alcoholic fatty liver diseases (NAFLD). Sex steroids, nuclear receptors, translational research

Researcher

Marine ADLANMERINI

Post-Doc,  INSERM researcher since Decembre 2021

Career path
Marine ADLANMERINI received her PhD in Physiology at the university of Toulouse (FR) in 2015. From 2016 to 2020, she worked as a post-doctoral fellow in the laboratory of Mitch Lazar in Philadelphie (USA) and then joined I2MC at Toulouse in 2021. She was recruited at the position of CRCN (tenured researcher) at the Inserm in Decembre 2021.

Main domains of expertise
Nuclear receptor (ER and REV-ERB), estrogen, circadian rhythms, metabolism, in vivo approaches.

Reseachers

Jean-François ARNAL

Jean-Francois ARNAL, Professor of Physiology

Jean-François ARNAL is professor in Physiology at Toulouse 3 University of Medicine and at Toulouse University Hospital since 1997, after a doctorate in medicine (1990), and a doctorate in physiopathology (1993) followed with a post-doctoral internship at the ‘Emory University at Atlanta (1994). He led the team until 2019 studying the structure-function relationships for optimization of Estrogen Receptor Alpha (ERα) modulation in medicine, summarized in the review: Membrane and Nuclear ERα 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 Jul 1; 97 (3): 1045-1087. PMID: 28539435. He is a foreign member of the Royal Academy of Medicine of Belgium (2020). He collaborates with Mithra Pharmaceuticals on Estetrol (E4) in oral contraception He obtained the Lamonica Prize for Cardiology of the Academy of Sciences in 2019. He is also a professor in physiology in PACES / PASS and in the 2nd year of medicine and is co-responsible for the Master resaerch  in physiopathology: from molecular to medical, and prepare future M.D. students in 2nd year of medicine at the INSERM School and at the ” MD-PhD training program ”. Videos M2 level: Role of estrogens in cardiovascular diseases – Jean-François ARNAL – Dec 2018 https://www.youtube.com/watch?v=C_Gq8xIWubM

Researcher

Coralie FONTAINE

CRCN (research fellow, normal class) at INSERM

Develops research on the impact of estrogen receptor (ER)a modulation on the arterial wall with implications for vascular pathologies such as atherosclerosis.

Career path
D. in biochemistry and molecular biology at the University of Lille (2002-2006), Postdoc at the University of Nice (2007-2008), joined the I2MC in Toulouse in 2008 and was recruited as a research fellow at Inserm in 2010.

Field of expertise 
Nuclear receptor, estrogen, endothelium, in vivo approaches.

 

Researcher

Alexandra MONTAGNER

INSERM researcher

Career path
After her PhD in Cellular Signaling (2006), Alexandra joined Pr Walter Wahli’s lab in Lausanne at the CIG (Center for Integrative Genomics) where she studied PPARb/d molecular function in skin carcinoma. In 2011, she then worked as a post-doc in Dr Hervé Guillou’s lab (INRA/ToxAlim, Toulouse) where she investigated PPARs specific function in hepatocytes during Non-Alcoholic Fatty Liver Diseases development (NAFLD). Since 2016, her research aims to decipher the impact of estrogens on the sexual dimorphism described in hepatic physiological functions and Non-Alcoholic Fatty Liver Diseases (NAFLD) progression together with Pr Pierre Gourdy.

Main domain of expertise
Nuclear Receptors, Liver, non-alcoholic fatty liver diseases (NAFLD), Estrogens.

CLINICIAN

Elodie CHANTELAT

CLINICIAN

Xavier GAME

CLINICIAN

Emmanuelle NOIRRIT-ESCLASSANC

Lecturer – Hospital practitioner

Career path

Master of Biological and Medical Sciences at the University Paul Sabatier Toulouse III (1995-1998). State Diploma of Doctor of Dental Surgery (1999). Diploma of Advanced Studies in Social Anthropology and History of Europe (École des Hautes Études en Sciences Sociales) (2000). PhD (LU Interface Biomaterials Biological Tissues) (2009). Joined in 2015.

Areas of expertise
Her research focuses on the study of pathophysiological mechanisms involved in the thromboembolic and bone effects of estrogens in the context of hormonal treatment of menopause and ageing.

Email:emmanuelle.noirrit@inserm.fr

Tél/Phone:06.61.96.84.35

CLINICIAN

Florence TREMOLIERES

Endocrinologist, MD.PHD, PU-PH in Medical Gynecology

Career path

Doctorate in Medicine in 1989, speciality Endocrinology and Metabolic Diseases. Post-doctoral training (1989-1991) in the Department of Bone Mineral Metabolism (Pr. D.J. Baylink), University of Loma Linda (California – USA). University thesis in Developmental Biology at the University Paul Sabatier (Toulouse III) in 1995. Habilitation to direct research (HDR) in 2002. She joined Team 9 (Dr. Françoise Lenfant, Pr. Pierre Gourdy) of the I2MC in 2006 as a clinician. Head of department since 2011 of the Menopause Centre, the only university centre in France dedicated to menopausal women. Founding member (2009) and President of the Study Group on Menopause and Hormonal Aging (GEMVi) (2019). Member of the boards of the European Menopause and Andropause Society (EMAS) (2009-2015) and of the International Menopause Society (IMS) (2014-2018). Officer of the Palmes Académiques (2017).

Area of expertise 

Study of the tissue consequences of estrogen deficiency states, particularly in terms of bone, cardiovascular and oncology in the post-menopause. Specialist in post-menopausal osteoporosis and metabolic bone pathologies.

She is a regular speaker at national and international congresses on the subjects of menopause and osteoporosis and is the author of more than 170 articles published in international or national referenced journals and of more than 15 book chapters.

CLINICIAN

Marie VALERA

Lecturer – Hospital practitioner

Career path

2005 : PhD in Dental Surgery. Paul Sabatier University (UPS) Toulouse III. 2005-2006: Master 2 Research. Mention Cellular and Integrated Physiology-Physiopathology.UPS Toulouse III. 2006-2009: University Doctorate in Cellular, Molecular and Integrated Physiopathology. INSERM U1048, I2MC. 2016 : Recruitment as Senior Lecturer/Hospital Practitioner.

Her current research focuses on understanding the pathophysiological mechanisms involved in the effects of estrogens on blood platelets and thrombosis in mouse models.

Area of expertise 
Haematology, animal experimentation, microsurgery

CLINICIAN

Alexia VINEL

Lecturer – Hospital practitioner

Career path

Master 2 Research and PhD in Biology-Health-Biotechnology at the University Paul Sabatier Toulouse III (2011-2015), post-doctorate at the I2MC Toulouse (2015-2018), MCU-PH at the Faculty of Dental Surgery and at the Toulouse University Hospital (since 2018).

Field of expertise

Bone tissue, estrogen receptors

Engineer

Mélissa BUSCATO

Engineer

Career path

Holder of a BTS BioAnalyses and Controls at the Saliège high school in Balma and an engineering degree in Sciences and Life of the Earth at the EPHE. She joined I2MC on a fixed-term contract in 2011.

She works as an engineer in the team on the study of vascular and metabolic effects of estrogens and SERMs.

Field of expertise 
Animal experimentation, cellular and molecular biology, histology.

Engineer

Adrien GARGAROS

Contractual study engineer at INSERM

Adrien Gargaros’ project focuses on the study of estrogen receptors in endometriosis lesions and the implementation of a new model for studying the pathology.

Career path

Master of Biology and Health specializing in Physiopathology at the University of Toulouse (2020). Study engineer since 2021.

Areas of expertise

Cell and molecular biology, Cell culture, Imaging, Animal experimentation, Estrogen receptor

Engineer

Silveric GILARDI

Engineer

Career path

Holder of a Master’s degree in Biology-Health with a major in Physiopathology from the University Paul Sabatier, Toulouse, France after a university training in Toulouse.

He joined the team in September 2020 and works on the modulation of the oestrogen receptor in physiology and physiopathology, studying the effect of endocrine disruptors (ANSES funding).

Field of expertise 

Animal experimentation, cellular and molecular biology, histology, cytometry

PhD Student

Morgane DAVEZAC

PhD Student

Career path

Master degree in Health Biology option Pathophysiology from Paul Sabatier University, Toulouse, France in 2018.

Morgane Davezac joined our team during her master degree in Health Biology option Pathophysiology from Paul Sabatier University, Toulouse, France in 2018. She is currently a PhD student working on the vascular effects of estrogens and SERMs under the direction of Pr. Jean-François Arnal and Dr. Coralie Fontaine.

Main domains of expertise

Animal experiments, Vascular biology, Microscopy, Cellular & Molecular Biology

PhD Student

Chanaëlle FEBRISSY

PhD student (ANR and Ligue contre le cancer funding)

Career path

Master’s degree in Genes, Cells and Development obtained at Paul Sabatier University (UT3) in 2018. PhD student since November 2018.

Chanaëlle Fébrissy is a PhD student working on the identification of molecular and cellular mechanisms involving the estrogen receptor ERα during tumor angiogenesis.

Field of expertise 

Molecular and cellular biology, animal experimentation, imaging, cytometry.

PhD Student

Mariam RUSIDZE

PhD student

Career path

Mariam Rusidze is an anatomo-pathologist who graduated from Tbilisi State Medical University in Georgia. She joined our team in 2018 as a Master2 Research student in Physiopathology from Paul Sabatier University. Currently a PhD student since October 2018, she is working on the physiology and pathophysiology of the estrogen receptor ERα in the reproductive system, fertility, as well as in endometriosis.

She received her M.D. in pathological anatomy- clinical pathology” – from Tbilisi State Medical University, Tbilisi (Georgia) and her Master degree in Physiopathology-from molecular to medical as an Erasmus student from Toulouse University III- Paul Sabatier, Toulouse in 2018. She recently obtained her Inter University Diploma (DIU) in Molecular Pathology at the University of Toulouse III-Paul Sabatier, Toulouse (2021).

Area of expertise

Human and murine histopathology diagnosis, animal experimentation, mouse ultrasound, imaging, molecular biology (RT-qPCR, RNAscope)

PhD Student

Blandine TRAMUNT

MD in Endocrinology, Diabetology & Metabolic Diseases
PhD student

Career path
Blandine Tramunt has performed her medical school in Toulouse. After completing her residency in Endocrinology, Diabetology and Metabolic Diseases at the CHU of Toulouse, she then pursued for 2 years her fellowship in the department of Diabetology, Metabolic Diseases and Nutrition at Toulouse University Hospital. After a master degree in Pathophysiology, she is performing her PhD within the team. Her research focuses on the sexually dimorphic role of estrogens in liver physiology and in Non-Alcoholic Fatty Liver Disease progression.

Main domain of expertise
Diabetes, non-alcoholic fatty liver diseases (NAFLD), Sex steroids, Nuclear Receptors

Student

Ana Gracia ALVAREZ TENA

MD in Endocrinology, Diabetes & Nutrition
Master Degree student

Career path
Ana has performed her medical school in Toulouse. After her residency in Endocrinology, Diabetology and Metabolic Diseases at the CHU of Toulouse and her MD (2020), Ana achieved a master degree in Physiopathology. Her research activity aims at understanding hepatocyte ERa function in lipid metabolism.

Main domain of expertise
Liver, Sexual dimorphism, Estrogens, Lipid and glucose metabolism

Student

Aurélie BUFFETEAU

Clinician – Master 2 – SFE funding (NSFA contract)

Aurélie Buffeteau’s project is the study of oestrogen receptors in endometriosis lesions and the establishment of new models to study the pathology.

Career path

Doctorate in medicine (speciality gynaecology-obstetrics) at the University of Toulouse Purpan (2020).

Student in Master 2 Surgical Sciences (University of Paris Créteil – UPEC) (2021)

Areas of expertise

Endometriosis, diagnosis and therapeutic strategies, cell biology, estrogen receptor.

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

THEY ARE SUPPORTING OUR RESEARCH

logotype i2mc
logotype i2mc

Inserm/UPS UMR 1297 - I2MC Institut des Maladies Métaboliques et Cardiovasculaires

1 avenue Jean Poulhès - BP 84225 - 31432 Toulouse Cedex 4

Tél. : 05 61 32 56 00

Contactez-nous

 

Horaires

Du lundi au vendredi
8h30 - 12h30 / 13h45 -16h45