Joëlle Cohen-Tannoudji

Unniversité Paris Cité

Background: The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcriptio...

Estradiol (E2) is a major hormone-controlling folliculogenesis whose dysfunction may participate in polycystic ovary syndrome (PCOS) infertility. To determine whether both the concentration and action of E2 could be impaired in non-hyperandrogenic overweight PCOS women, we isolated granulosa cells (GCs) and follicular fluid (FF) from follicles of w...

Disclosure: M. Devillers: None. C.M. François: None. M. Chester: None. R. Corre: None. V. Cluzet: None. F. Giton: None. J. Cohen-Tannoudji: None. C.J. Guigon: None. Introduction: In females, androgens contribute to ovarian diseases such as polycystic ovary syndrome (PCOS), but their action is also crucial for ovarian physiology, i.e., follicular gr...

Disclosure: M. Chester: None. M. Devillers: None. L. Naule: None. F. Souaré: None. R. Corre: None. D. Quintas: None. C. Petrovic: None. J. Cohen-Tannoudji: None. S. Mhaouty-Kodja: None. C.J. Guigon: None. After birth, there is a transient activation of the hypothalamic-pituitary-ovary (HPO) axis, with high secretion of LH and FSH acting on the ovar...

Pituitary gonadotrope cells are essential for the endocrine regulation of reproduction in vertebrates. These cells emerge early during embryogenesis, colonize the pituitary glands and organize in tridimensional networks, which are believed to be crucial to ensure proper regulation of fertility. However, the molecular mechanisms regulating the organ...

In females, androgens contribute to ovarian diseases such as polycystic ovarian syndrome (PCOS), but their action is also crucial for ovarian physiology, i.e., follicular growth and estradiol (E2) synthesis during reproductive life, in interaction with the gonadotropins LH and FSH. However, it is unclear whether androgens already play a role in the...

L’œstradiol (E2), produit par les cellules de la granulosa (CG) des follicules ovariens, joue un rôle essentiel dans la folliculogenèse. L’E2 agit majoritairement via deux récepteurs nucléaires, ERα et ERβ, qui se fixent à l’ADN sur des séquences spécifiques, principalement de type ERE (élément de réponses aux œstrogènes) et/ou AP1 (protéine d’acti...

Overnutrition is associated with the activation of inflammatory pathways in metabolically linked organs and an early hypothalamic inflammation is now known to disrupt the central control of metabolic function. Because we demonstrated that fatty acids (FA) target the pituitary and affect gonadotropin synthesis, we asked whether overnutrition induces...

Estradiol (E2) is a major hormone controlling women fertility, in particular folliculogenesis. This steroid, which is locally produced by granulosa cells (GC) within ovarian follicles, controls the development and selection of dominant preovulatory follicles. E2 effects rely on a complex set of nuclear and extra-nuclear signal transduction pathways...

Toxic effects of nanoparticles on female reproductive health have been documented but the underlying mechanisms still need to be clarified. Here, we investigated the effect of carbon black nanoparticles (CB NPs) on the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are key regulators of gonadal gamet...

Granulosa cell tumor (GCT) is a form of ovarian tumor characterized by its tendency to recur years after surgical ablation. Little is known on the mechanisms involved in GCT development and progression. GCTs can produce estradiol (E2), but whether this hormone could play a role in this cancer through its nuclear receptors, i.e., ERα and ERβ, remain...

Estrogen receptor beta (ERβ) plays a critical role in granulosa cell (GC) functions. The existence of four human ERβ splice isoforms in the ovary suggests their differential implication in 17β-estradiol (E2) actions on GC apoptosis causing follicular atresia. In this study, we investigated whether E2 can regulate ERβ isoforms expression to fine tun...

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) r...

Ovarian granulosa cell tumors (GCTs) are indolent tumors of the ovary affecting women at all ages and potentially displaying late recurrence. Even if there is still little information regarding the mechanisms involved in GCT development and progression, FOXL2 would be a major tumor suppressor gene in granulosa cells. We analyzed the mechanisms unde...

Background: Gonadotrope lineage differentiation is a stepwise process taking place during pituitary development. The early step of gonadotrope lineage specification is characterized by the expression of the Nr5a1 transcription factor, a crucial factor for gonadotrope cell fate determination. Abnormalities affecting Nr5a1 expression lead to hypogon...

Cancer is a multifactorial condition with aberrant growth of cells. A substantial number of cancers, breast in particular, are hormone sensitive and evolve due to malfunction in the steroidogenic machinery. Breast cancer, one of the most prevalent form of cancers in women, is primarily stimulated by estrogens. Steroid hormones are made from cholest...

Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature FSH-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by el...

Background/objectives: Anti-Müllerian hormone (AMH) signaling is critical for sexual differentiation and gonadal function. AMH receptor type 2 (AMHR2) is expressed in extragonadal sites such as brain and pituitary and emerging evidence indicates that AMH biological action is much broader than initially thought. We recently reported that AMH signali...

Les microARN (miARN) sont des acteurs majeurs dans la régulation des gènes et l’expression des phénotypes cellulaires. Ils sont également activement sécrétés et certains sont considérés comme des marqueurs de pathologies. Les miARN circulants peuvent être captés par d’autres cellules, leur conférant un rôle dans les communications intercellulaires....

Le syndrome des ovaires polykystiques (SOPK), première cause d’infertilité féminine, est défini par les trois critères de Rotterdam : oligo-anovulation, hyperandrogénie, aspect polykystique des ovaires ; associés avec une prévalence augmentée de l’insulinorésistance, de l’obésité viscérale et du diabète de type 2. L’étude de ce syndrome est rendue...

Chez les mammifères, le gène Sf-1 est essentiel à la fonction de reproduction. Dans l’hypophyse, il est exprimé dans les cellules gonadotropes. Au cours de la spécification de ce lignage il régule l’expression de gènes clefs comme ceux du récepteur de la GnRH ou des gonadotropines. La régulation de son expression est donc critique pour l’établissem...

Reproductive function is under the control of the neurohormone GnRH, which activates a G-protein-coupled receptor (GnRHR) expressed in pituitary gonadotrope cells. GnRHR activates a complex signaling network to regulate synthesis and secretion of the two gonadotropin hormones, luteinizing hormone and follicle-stimulating hormone, both regulating ga...

Glucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC s...

Context Anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) are overexpressed in granulosa cells (GCs) from women with polycystic ovary syndrome (PCOS), the most common cause of female infertility. Objective The aim of the study was to compare the regulation of the AMH/AMHR2 system by 5α-dihydrotestosterone (5α-DHT) and estradiol (E2) in...

Estradiol (E2) secretion by human granulosa cells can be disrupted by various environmental toxicants. In the present study, we investigated whether carbon black nanoparticles (CB NPs) affect the steroidogenic activity of cultured human granulosa cells. The human granulosa cell line KGN and granulosa cells from patients undergoing in vitro fertiliz...

In cyclic females, FSH stimulates ovarian estradiol (E2) production and follicular growth up to the terminal stage. A transient elevation in circulating FSH and E2 levels occurs shortly after birth. But what could be the action of FSH on the ovary during this period, and in particular how it stimulates ovarian steroidogenesis without supporting ter...

L’objectif principal du projet "NANOVHYP" était d’évaluer la toxicité des nanoparticules de noir de carbone sur la fonction endocrine de l’hypophyse et des gonades femelles, les ovaires. Les modèles utilisés étaient des cellules ou des souris exposées par instillation intra-trachéale, simulant l’inhalation.

Scientific Reports 6 : Article number: 31563 10.1038/srep31563 ; published online: 19 August 2016 ; updated: 05 October 2016 The original version of this Article contained a typographical error in the spelling of the author Joëlle Cohen-Tannoudji, which was incorrectly given as Joelle-Cohen-Tannoudji.

Context: Anti-Müllerian Hormone (AMH) is an important clinical marker for diagnosing and assessing reproductive status and/or disorders in men and women. Most studies have not distinguished between levels of inactive AMH precursor and the cleaved noncovalent complex that binds the AMH type II receptor, AMHRII, and initiates signaling. Objective:...

Introduction La mini-puberte correspond a une phase d’activation temporaire de l’axe gonadotrope ; elle survient juste apres la naissance chez les mammiferes. L’elevation importante des niveaux des gonadotropines LH et FSH s’accompagne chez la femelle de la production d’œstradiol (E2) par des follicules immatures. L’E2 infantile participerait notam...

The GnRH neurohormone is the main activator of the pituitary gonadotropins, LH and FSH. Here we investigated the contribution of microRNAs in mediating GnRH activation. We first established that miR-125b targets several actors of Gαq/11 signalling pathway, without altering Gαs pathway. We then showed that a Gαs-mediated, PKA-dependent phosphorylati...

Gonadotrope cell identity genes emerge in a stepwise process during mouse pituitary development. Cga, encoding for the α-subunit of TSH, LH, and FSH is initially detected at E11.5 followed by Gnrhr and steroidogenic factor Sf1 at E13.5, specifying cells engaged in a gonadotrope cell fate. Lhb and Fshb appear at E16.5 and 17.5, respectively, typifyi...

Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH s...

Granulosa cell tumor (GCT) is a rare and severe form of sex-cord stromal ovarian tumor that is characterized by its long natural history and tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ~20% of patients die of the consequences of their tumor. However, very little is known of the m...

Gonadotropin-releasing hormone (GnRH) plays a key role in the vertebrate reproductive system by stimulating biosynthesis and secretion of pituitary gonadotropins. However, the potential involvement of microRNAs (miRNAs) on this activation has still to be explored. In this study, we investigated the role of miRNA-132 and miRNA-212, two tandemly expr...

Friedreich Ataxia (FA), the most common inherited autosomal recessive ataxia in Caucasians, is characterized by progressive degeneration of the central and peripheral nervous system, hypertrophic cardiomyopathy and increased incidence of diabetes. FA is caused by a GAA repeat expansion in the first intron of the gene encoding frataxin, an evolution...

L’essor des nanotechnologies entraîne un accroissement de l’exposition des populations aux nanoparticules manufacturées issues de matériaux variés, qui s’ajoutent à celles produites non intentionnellement. Parmi les nanoparticules, celles de noir de carbone sont largement utilisées dans l’industrie (ex. pneumatiques et autres caoutchoucs, plastique...

Thyroid-stimulating hormone (TSH) is composed of a specific β subunit and an α subunit that is shared with the two pituitary gonadotropins. The three β subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant...

Aberrant loss of oocytes following cancer treatments or genetic mutations leads to premature ovarian insufficiency (POI) associated with endocrine-related disorders in 1% of women. Therefore, understanding the mechanisms governing oocyte death is crucial for the preservation of female fertility. Here, we report the striking reproductive features of...

Reproductive function is highly dependent on nutritional input. We recently provided evidence that the unsaturated ω6 fatty acid, linoleic acid (linoleic), interferes with transcription and secretion of the gonadotropin LH, highlighting the existence of a lipid sensing in pituitary gonadotropes. Here, we show using a combination of in vivo and in v...

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified i...

Granulosa cell tumor (GCT) is a rare but severe form of ovarian tumor that is characterized by its tendency to recur years after surgical ablation. Because there is no efficient curative treatment beyond surgery, ∼20% of adult patients die of the consequences of their tumor. However, very little is known of the molecular etiology of this pathology....

Peptide stability on mass spectrometry-coupled electrospray (Quattro-LC). Peptides were measured in aqueous solution at pH 7 and starved overnight at 37°C. WT and R31C decapeptides are found at the expected molecular weights (1181.6 and 1128.5, respectively). Formation of smaller fragments was absent in WT and negligible in R31C. Formation of R31C...

Luciferase activity after pulsatile exposure. HEK293T cells were transiently transfected with GNRHR and SRE-coupled luciferase reporter gene, and then exposed to four 90 min-spaced pulses of 10 nM WT, 10 nM R31C and 10+10 nM WT+R31C. After 5 minutes exposure to each ligand, cells were washed, and a subsequent pulse was given 90 minutes after. Five...

Primer sets used for experiments. (DOC)

Genomic localization of human GNRH1 and related transcription and translation products. Two main regulatory regions are located upstream the trascription start site: the proximal promoter mainly regulates hypothalamic trascript, whereas the distal promoter controls a longer GNRH1 transcript (retaining entire intron 1 sequence) in the extra-cerebral...

The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying gonad-specific expression of the Gnrhr are not well understood. Here, Gnrhr expression was analysed in developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene...

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified i...

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of cholesteryl esters in steroidogenic tissues and, thus, facilitates cholesterol availability for steroidogenesis. The steroidogenic acute regulatory protein (StAR) controls the rate-limiting step in steroid biosynthesis. However, the modes of action of HSL in the regulation of StAR expressio...

The GnRH receptor (GnRHR) plays a central role in the development and maintenance of reproductive function in mammals. Following stimulation by GnRH originating from the hypothalamus, GnRHR triggers multiple signaling events that ultimately stimulate the synthesis and the periodic release of the gonadotropins, luteinizing-stimulating hormone (LH) a...

In mammals, the receptor of the neuropeptide gonadotropin-releasing hormone (GnRHR) is unique among the G protein-coupled receptor (GPCR) family because it lacks the carboxyl-terminal tail involved in GPCR desensitization. Therefore, mechanisms involved in the regulation of GnRHR signaling are currently poorly known. Here, using immunoprecipitation...