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International audience; Hypercortisolism usually occurs in women of childbearing age. Even if hypercortisolism theoreticallyleads to infertility, due to altered mechanisms of GnRH secretion, pregnancy can happen.Endocrinologists should be aware of the management of this situation in this context, as it may leadto serious comorbidities for both the mother (gestational diabetes, hypertension...) and the fetus(intra-uterine growth retardation, early birth...). Cushing’s syndrome can also happen duringpregnancy: the comorbidities are the same, but the diagnosis is usually very difficult to perform dueto hormonal changes especially due to hyperestrogenism. This review will detail the mechanismsleading to infertility in women with Cushing’s syndrome, the risks of hypercortisolism duringpregnancy, the methods to diagnose Cushing’s syndrome during pregnancy, and the methods ofcontraception.; Le syndrome de Cushing se définit par un hypercortisolisme endogène ou exogène. L’augmentationde sécrétion du cortisol va avoir un impact négatif sur la sécrétion pulsatile de GnRH.L’hyperandrogénie pouvant être associée va également avoir un impact sur la GnRH, ces 2mécanismes aboutissant à un sur-risque d’infertilité. En cas de grossesse survenant chez unepatiente présentant un syndrome de Cushing, de nombreuses conséquences vont pourvoir êtreobservées chez la mère (avec un sur-risque de diabète gestationnel, hypertension artérielle,éclampsie... en sus des complications propres à l’hypercortisolisme) et chez le fœtus (retard decroissance intra-utérin, prématurité...). Il s’agit cependant d’un évènement rare, de diagnosticdifficile, du fait de nombreuses modifications hormonales induites par la grossesse sur le cortisol.L’objectif de cette revue est de détailler les mécanismes de l’infertilité, les méthodes diagnostiquesde syndrome de Cushing pendant la grossesse, les conséquences materno-fœtales, ainsi que lesmoyens de contraception pouvant être proposés.

Le craniopharyngiome est une tumeur épithéliale bénigne prenant naissance dans le cerveau, plus précisément au niveau de l’hypophyse ou de la tige pituitaire. Cette maladie bien que rare, affecte une personne sur cinquante mille. Elle peut être découverte à n’importe quel âge de la vie puisque cette pathologie silencieuse à ses débuts, passe souvent inaperçue en raison de symptômes peu spécifiques. Il s’agit toutefois d’une maladie grave puisqu’elle peut entrainer à terme des séquelles endocriniennes, visuelles, ou neuro intellectuelles. Le craniopharyngiome nécessite une prise en charge à la fois médicale et thérapeutique. Dans un premier temps, le traitement consiste en l’exérèse la plus complète possible de la tumeur mais la proximité immédiate de l’hypophyse avec des structures essentielles en fait une chirurgie très délicate et non dénuée de risque. Outre les risques inhérents à l’opération, le retrait de la tumeur conduit à un dysfonctionnement hypothalamo-hypophysaire plus ou moins complet.

Commercial gonadotropin-releasing hormone (GnRH) antagonists differ by 1&ndash, 2 amino acids and are used to inhibit gonadotropin production during assisted reproduction technologies (ART). In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro. GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary L&beta, T2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist. We evaluated intracellular calcium (Ca2+) and cAMP increases, cAMP-responsive element binding-protein (CREB) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation, &beta, catenin activation and mouse luteinizing-hormone &beta, encoding gene (Lhb) transcription by bioluminescence resonance energy transfer (BRET), Western blotting, immunostaining and real-time PCR as appropriate. The kinetics of GnRH-induced Ca2+ rapid increase revealed dose-response accumulation with potency (EC50) of 23 nM in transfected HEK293 cells, transfected SH-SY5Y and L&beta, T2 cells. Cetrorelix inhibited the 3 &times, EC50 GnRH-activated calcium signaling at concentrations of 1 nM&ndash, 1 &micro, M, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM&ndash, M range in both transfected HEK293 and SH-SY5Y cells in vitro. In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation. All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in L&beta, T2 and transfected HEK293 cells treated with 100 nM GnRH. Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 &micro, M GnRH-induced &beta, catenin activation, Lhb gene expression increase occurring upon L&beta, T2 cell treatment by 1 &micro, M GnRH was similarly inhibited by all antagonists. To conclude, this study has demonstrated Cetrorelix-, Ganirelix- and Teverelix-specific biased effects at the intracellular level, not affecting the efficacy of antagonists in inhibiting Lhb gene transcription.

The anterior pituitary is a master endocrine gland producing 6 hormones (GH, TSH, ACTH, PRL, FSH and LH) that regulate essential life processes such as growth (GH), metabolism (TSH), stress response (ACTH), puberty and reproduction (FSH/LH and PRL), thyroid function (TSH) and lactation (PRL). In the human, mutations in SHH, BMP4 and FGF8 genes encoding morphogenes and GLI2, LHX3, LHX4, HESXJ, SOX2 and SOX3 genes encoding transcription factors implicated in pituitary ontogenesis are responsible for isolated (IGHD) or combined (CPHD) pituitary hormone deficit(s) that can be syndromic. The incidence of those deficits is close to 1/8,000 births. So far, mutations reported in about thirty genes explain only 25% of the cases.The first goal of this thesis was to identify new genes responsible for pituitary hormone deficits through a candidate gene approach, and by whole-exome sequencing coupled with homozygosity mappini, using a large cohort of more than 3000 DNA samples collected by the laboratory since 1997. The candidate gene approach, led to the identification of variations in NOG, VAXJ and GSXJ, all involved in mouse pituitary ontogenesis, and we identified potentially key genes for pituitary development.The other aim of this work was to characterize the function of LHX4, GHRHR, GL/2 and GSXJ through the functional evaluation of the variants identified in the laboratory. The implication of new disease-causing genetic variants in LHX4, GHRHR and GL/2 allowed us to delineate the phenotypic spectrum associated with mutations for each gene, and also to precise the role of LHX4 in the complex molecular network required for proper pituitary development.A better understanding of the molecular mecanisms involved in pituitary formation should lead to new ways for management of this heterogenous condition, including genetic counseling and therapeutic decisions in affected families, L'antehypohyse est une glande endocrine maitresse produisant 6 hormones (GH, TSH, ACTH, PRL, FSH et LH) qui regulent des processus vitaux comme la croissance et le metabolisme (GH et TSH), la reponse au stress (ACTH), la puberte et la reproduction (FSH, LH et PRL), la fonction thyroidienne (TSH) et la lactation (PRL). Chez l'Homme, des mutations des genes SHH, BMP4 et FGF8, codant pour des morphogenes, et de GLI2, LHX3, LHX4, HESXJ, SOX2 et SOX3, codant pour des facteurs de transcription impliques dans l'ontogenese pituitaire sont responsables de deficit(s) isole (IGHD) ou multiples (CPHD) en hormones antehypophysaires, pouvant etre syndromique(s). L'incidence de ces deficits est d'environ 1/8000 naissances. A ce jour, des mutations rapportees dans une trentaine de genes permettent d'expliquer cette affection chez seulement 25% des patients.Le premier objectif de ce travail de these etait d'identifier de nouveaux genes responsables de deficit antehypophysaire par une approche « genes candidats », et par des analyses d'exome couplees a une cartographie par homozygotie a partir d'une cohorte de plus de 3000 ADNs colliges par le laboratoire depuis 1997. L'approche « genes candidats » nous a permis de mettre en evidence des variations dans les genes NOG, VAX1 et GSX1, impliques dans l'ontogenese pituitaire murine, et identifier d'autres genes potentiellement cles dans le developpement de l'hypophyse. L'autre objectif etait de caracteriser la fonction de LHX4, GHRHR, GLI2 et GSX1 a travers l'etude fonctionnelle des variants identifies au laboratoire. L'implication de nouveaux variants genetiques de LHX4, GHRHR et GLI2 a permis de preciser le spectre phenotypique associe aux mutations de chacun de ces genes, et aussi de preciser le role de LHX4 dans le reseau moleculaire complexe necessaire a la formation de l'hypophyse. La comprehension des mecanismes moleculaires a l'origine du developpement pituitaire devrait permettre a terme une meilleure prise en charge de cette pathologie tres heterogene, incluant le conseil genetique des familles concernees et le traitement des patients

Remerciements :INRA, UMR PRC 0085, Plateforme CIRE, 37380 NouzillyStephane Fabre and Alan McNeilly for helpful discussionYves Combarnous for helpful suggestions, Maxime Capelle and Marie Champion for technical assistanceElodie Chaillou for critical reading of the manuscript; Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during embryogenesis and in adulthood including cell differentiation, proliferation and death in various tissues. In the adult pituitary, BMPs participate in the control of hormone secretion and cell proliferation suggesting a potential endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here, using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a BMP-responsive element, we sought to determine whether pituitary cells secrete BMPs or BMP antagonists. Interestingly, we found that pituitary-conditioned medium contains a factor that inhibits action of BMP-2 and -4. Combining surface plasmon resonance (SPR) and high-resolution mass spectrometry helped pinpoint this factor as thrombospondin-1 (TSP-1). SPR and co-immunoprecipitation confirmed that recombinant human TSP-1 can bind BMP-2 and -4 and antagonize their effects on C3H10T1/2 cells. Moreover, TSP-1 inhibited the action of serum BMPs. We also report that the von Willebrand type C (VWC) domain of TSP-1 is likely responsible for this BMP-2/4 binding activity, an assertion based on sequence similarity that TSP-1 shares with the VWC domain of Crossveinless 2 (CV-2), a BMP antagonist and member of the chordin family. In summary, we identified for the first time TSP-1 as a BMP-2/-4 antagonist and presented structural basis for the physical interaction between TSP-1 and BMP-4. We propose that TSP-1 could regulate bioavailability of BMPs, either produced locally or reaching the pituitary via the blood circulation. In conclusion, our findings provide new insights into the involvement of TSP-1 in the BMP-2/-4 mechanisms of action.

The anterior pituitary is a master endocrine gland producing 6 hormones (GH, TSH, ACTH, PRL, FSH and LH) that regulate essential life processes such as growth (GH), metabolism (TSH), stress response (ACTH), puberty and reproduction (FSH/LH and PRL), thyroid function (TSH) and lactation (PRL). In the human, mutations in SHH, BMP4 and FGF8 genes encoding morphogenes and GLI2, LHX3, LHX4, HESXJ, SOX2 and SOX3 genes encoding transcription factors implicated in pituitary ontogenesis are responsible for isolated (IGHD) or combined (CPHD) pituitary hormone deficit(s) that can be syndromic. The incidence of those deficits is close to 1/8,000 births. So far, mutations reported in about thirty genes explain only 25% of the cases.The first goal of this thesis was to identify new genes responsible for pituitary hormone deficits through a candidate gene approach, and by whole-exome sequencing coupled with homozygosity mappini, using a large cohort of more than 3000 DNA samples collected by the laboratory since 1997. The candidate gene approach, led to the identification of variations in NOG, VAXJ and GSXJ, all involved in mouse pituitary ontogenesis, and we identified potentially key genes for pituitary development.The other aim of this work was to characterize the function of LHX4, GHRHR, GL/2 and GSXJ through the functional evaluation of the variants identified in the laboratory. The implication of new disease-causing genetic variants in LHX4, GHRHR and GL/2 allowed us to delineate the phenotypic spectrum associated with mutations for each gene, and also to precise the role of LHX4 in the complex molecular network required for proper pituitary development.A better understanding of the molecular mecanisms involved in pituitary formation should lead to new ways for management of this heterogenous condition, including genetic counseling and therapeutic decisions in affected families, L'antehypohyse est une glande endocrine maitresse produisant 6 hormones (GH, TSH, ACTH, PRL, FSH et LH) qui regulent des processus vitaux comme la croissance et le metabolisme (GH et TSH), la reponse au stress (ACTH), la puberte et la reproduction (FSH, LH et PRL), la fonction thyroidienne (TSH) et la lactation (PRL). Chez l'Homme, des mutations des genes SHH, BMP4 et FGF8, codant pour des morphogenes, et de GLI2, LHX3, LHX4, HESXJ, SOX2 et SOX3, codant pour des facteurs de transcription impliques dans l'ontogenese pituitaire sont responsables de deficit(s) isole (IGHD) ou multiples (CPHD) en hormones antehypophysaires, pouvant etre syndromique(s). L'incidence de ces deficits est d'environ 1/8000 naissances. A ce jour, des mutations rapportees dans une trentaine de genes permettent d'expliquer cette affection chez seulement 25% des patients.Le premier objectif de ce travail de these etait d'identifier de nouveaux genes responsables de deficit antehypophysaire par une approche « genes candidats », et par des analyses d'exome couplees a une cartographie par homozygotie a partir d'une cohorte de plus de 3000 ADNs colliges par le laboratoire depuis 1997. L'approche « genes candidats » nous a permis de mettre en evidence des variations dans les genes NOG, VAX1 et GSX1, impliques dans l'ontogenese pituitaire murine, et identifier d'autres genes potentiellement cles dans le developpement de l'hypophyse. L'autre objectif etait de caracteriser la fonction de LHX4, GHRHR, GLI2 et GSX1 a travers l'etude fonctionnelle des variants identifies au laboratoire. L'implication de nouveaux variants genetiques de LHX4, GHRHR et GLI2 a permis de preciser le spectre phenotypique associe aux mutations de chacun de ces genes, et aussi de preciser le role de LHX4 dans le reseau moleculaire complexe necessaire a la formation de l'hypophyse. La comprehension des mecanismes moleculaires a l'origine du developpement pituitaire devrait permettre a terme une meilleure prise en charge de cette pathologie tres heterogene, incluant le conseil genetique des familles concernees et le traitement des patients

International audience; Visfatin and resistin appear to interfere with reproduction in the gonads, but their potential action at the hypothalamic-pituitary level is not yet known. The aim of the present study was to investigate the mRNA and protein expression of these adipokines in murine gonadotroph cells and to analyse the effects of different concentrations of recombinant mouse visfatin and resistin (0.01, 0.1, 1 and 10 ng mL(-1)) on LH secretion and signalling pathways in L beta T2 cells and/or in primary female mouse pituitary cells. Both visfatin and resistin mRNA and protein were found in vivo in gonadotroph cells. In contrast with resistin, the primary tissue source of visfatin in the mouse was the skeletal muscle, and not adipose tissue. Visfatin and resistin both decreased LH secretion from L beta T2 cells after 24 h exposure of cells (P < 0.03). These results were confirmed for resistin in primary cell culture (P < 0.05). Both visfatin (1 ng mL(-1)) and resistin (1 ng mL(-1)) increased AMP-activated protein kinase a phosphorylation in L beta T2 cells after 5 or 10 min treatment, up to 60 min (P < 0.04). Extracellular signal-regulated kinase 1/2 phosphorylation was transiently increased only after 5 min resistin (1 ng mL(-1)) treatment (P < 0.01). In conclusion, visfatin and resistin are expressed in gonadotroph cells and they may affect mouse female fertility by regulating LH secretion at the level of the pituitary.

Pituitary dysfunction is a late-delayed side effect of cranial radiotherapy. The object of this study was to evaluate radiation induced pituitary toxicity of proton beam therapy in a cohort of adult chondrosarcoma patients. The files of 113 patients were reviewed retrospectively. Mean age at the beginning of radiotherapy was 43 years old (18 to 76). Mean dose delivered to the tumor was 67 Gy and mean dose delivered to the pituitary gland was 59 Gy. Mean post radiotherapy follow up time was 7 years. 78 patients (69 %) presented with a pituitary dysfunction including hyperprolactinemia (40 %), thyrotrophic insufficiency (36 %), corticotropic insufficiency (31 %) and gonadotropic insufficiency (25 %). Pituitary anomalies were developed in more or less 4 years and no significant differences were shown between the axes for this delay. No cardiovascular risk factor was associated with pituitary insufficiency. Pituitary toxicity of radiotherapy is frequent after 4 years in this study. The high prevalence of hyperprolactinemia on diagnosis pinpoints a possible hypothalamic origin of post radiotherapy pituitary insufficiency. A prospective follow up is necessary to complete these observations.; L’insuffisance antéhypophysaire est une complication tardive de la radiothérapie des tumeurs cérébrales et de la base du crâne. L’objectif de cette étude était d’évaluer la toxicité antéhypophysaire dans une cohorte de patients adultes ayant eu une radiothérapie pour des chondrosarcomes de la base du crâne. Les dossiers de 113 patients ont été revus de façon rétrospective. L’âge moyen lors de la radiothérapie était de 43 ans (18 à 76). L’irradiation a délivré une dose moyenne de 67 Gy à la tumeur, et 59 Gy à l’hypophyse. La durée moyenne du suivi endocrinologique était de 7 ans (4 à 17). Une anomalie du bilan hypophysaire est survenue chez 78 patients (69%) à 4 ans de la radiothérapie. La prévalence des anomalies était de 40 % pour l’hyperprolactinémie, de 36 % pour l’insuffisance thyréotrope, de 31 % pour l’insuffisance corticotrope et 25 % pour l’insuffisance gonadotrope. Le délai d’apparition des anomalies pour les différents axes n’était pas significativement différent. En analyse multivariée, les facteurs de risque pouvant augmenter l’atteinte artérielle secondaire à la radiothérapie (sexe, âge, tabagisme, hypertension artérielle, dyslipidémie ou diabète sucré) n’étaient pas associés à un sur-risque d’insuffisance hypophysaire. La toxicité hypothalamo-hypophysaire de la radiothérapie est donc fréquente après 4 ans dans cette étude. Du fait de l’hyperprolactinémie se pose la question d’une atteinte hypothalamique première. Un suivi prospectif est nécessaire pour confirmer ces résultats et proposer des recommandations.

Numerous models have been proposed to explain the mechanisms of tumor development and progression. Nevertheless some aspects such as the nature and hierarchy of primary and secondary alterations are still debated. To answer these questions, we decided to focus on the tumoral progression of human prolactin pituitary tumors. These monoclonal tumors are usually benign but some present an aggressive or malignant phenotype. To identify the molecular events involved in tumoral progression of human PRL towards aggressive phenotype we used an integrative genomics approach (microarrays, high-throughput sequencing) coupling analysis of transcriptome, genome (variation in the number of chromosomal copy polymorphisms) and miRNome from the same human tumor. Using this strategy we identified and prioritized specific alterations of aggressive and / or malignant tumors in a model explaining the tumor progression of human prolactin pituitary tumors. We have shown that under-expression of micro-RNA miR-183, miR-744 and miR-98 stimulates proliferation through overexpression of their targets KIAA0101, TGFB1 and E2F2 specifically in aggressive tumors. This leads to the acquisition of chromosomal damage (loss of chromosome 11 and gain of chromosome 1q) which allowed the activation of the metastatic processes. Finally, this work shows that the integrative genomic multi-dimensional approach can provide new clues for the characterization of tumor phenotypes, diagnosis of aggressive tumors and prediction of tumor behavior, De nombreux modèles ont été proposés pour expliquer les mécanismes de développement et de progression tumorale, néanmoins certains aspects comme la nature et la hiérarchie des altérations primaires et secondaires sont encore discutés. Pour répondre à ces questions, nous nous sommes intéressés à la progression tumorale des tumeurs hypophysaires à prolactine humaines. Ces tumeurs d'origine monoclonale sont souvent bénignes mais certaines présentent un phénotype agressif voire malin. Afin d'identifier les mécanismes impliqués dans la progression vers le phénotype agressif nous avons utilisé des techniques de génomique intégrative (puces à ADN, séquençage haut débit) couplant l'étude du transcriptome, du génome (variation du nombre de copie chromosomique, polymorphismes) et du miRNome à partir des mêmes échantillons tumoraux. Par cette stratégie nous avons identifié et hierarchisé des altérations spécifiques des tumeurs agressives et / ou malignes dans un modèle expliquant la progression tumorale des tumeurs hypophysaires à prolactine humaines. Nous avons montré que la sous-expression des microARNs miR-183, miR-744 et miR-98 stimule la prolifération via la surexpression de leurs cibles KIAA0101, TGFB1 et E2F2 spécifiquement dans les tumeurs agressives. Ceci entraine l'acquisition d'altérations chromosomiques (perte du chromosome 11 et le gain du chromosome 1q) permettant l'activation de la dissémination métastatique. Enfin, ce travail montre que l'approche de génomique intégrative multidimensionnelle permet d'apporter de nouveaux éléments pour la caractérisation des phénotypes tumoraux, le diagnostic des tumeurs agressives et la prédiction du comportement tumoral

Numerous models have been proposed to explain the mechanisms of tumor development and progression. Nevertheless some aspects such as the nature and hierarchy of primary and secondary alterations are still debated. To answer these questions, we decided to focus on the tumoral progression of human prolactin pituitary tumors. These monoclonal tumors are usually benign but some present an aggressive or malignant phenotype. To identify the molecular events involved in tumoral progression of human PRL towards aggressive phenotype we used an integrative genomics approach (microarrays, high-throughput sequencing) coupling analysis of transcriptome, genome (variation in the number of chromosomal copy polymorphisms) and miRNome from the same human tumor. Using this strategy we identified and prioritized specific alterations of aggressive and / or malignant tumors in a model explaining the tumor progression of human prolactin pituitary tumors. We have shown that under-expression of micro-RNA miR-183, miR-744 and miR-98 stimulates proliferation through overexpression of their targets KIAA0101, TGFB1 and E2F2 specifically in aggressive tumors. This leads to the acquisition of chromosomal damage (loss of chromosome 11 and gain of chromosome 1q) which allowed the activation of the metastatic processes. Finally, this work shows that the integrative genomic multi-dimensional approach can provide new clues for the characterization of tumor phenotypes, diagnosis of aggressive tumors and prediction of tumor behavior, De nombreux modèles ont été proposés pour expliquer les mécanismes de développement et de progression tumorale, néanmoins certains aspects comme la nature et la hiérarchie des altérations primaires et secondaires sont encore discutés. Pour répondre à ces questions, nous nous sommes intéressés à la progression tumorale des tumeurs hypophysaires à prolactine humaines. Ces tumeurs d'origine monoclonale sont souvent bénignes mais certaines présentent un phénotype agressif voire malin. Afin d'identifier les mécanismes impliqués dans la progression vers le phénotype agressif nous avons utilisé des techniques de génomique intégrative (puces à ADN, séquençage haut débit) couplant l'étude du transcriptome, du génome (variation du nombre de copie chromosomique, polymorphismes) et du miRNome à partir des mêmes échantillons tumoraux. Par cette stratégie nous avons identifié et hierarchisé des altérations spécifiques des tumeurs agressives et / ou malignes dans un modèle expliquant la progression tumorale des tumeurs hypophysaires à prolactine humaines. Nous avons montré que la sous-expression des microARNs miR-183, miR-744 et miR-98 stimule la prolifération via la surexpression de leurs cibles KIAA0101, TGFB1 et E2F2 spécifiquement dans les tumeurs agressives. Ceci entraine l'acquisition d'altérations chromosomiques (perte du chromosome 11 et le gain du chromosome 1q) permettant l'activation de la dissémination métastatique. Enfin, ce travail montre que l'approche de génomique intégrative multidimensionnelle permet d'apporter de nouveaux éléments pour la caractérisation des phénotypes tumoraux, le diagnostic des tumeurs agressives et la prédiction du comportement tumoral

The embryology of the human adrenal and the pathogenesis of the hypoplasia adrenal congenital are complex and not well known. We studied the histological and functional characteristics of the fetal human adrenal in normal fetuses aged 12 to 36 weeks development (WD) and presented three cases of congenital adrenal hypoplasia with pituitary abnormalities. In the human fetal adrenal cortex, only the cells of the definitive zone proliferate from the 12th WD. We observe the expression of an adherence protein (NCAM) and of two steroidogenesis enzymes (3β-HSD and P450 c21) in the definitive zone cells, attesting to the capacity of these cells to synthesize mineralocorticoids and/or cortisol. In the fetal zone, only P450 c21 immunoreactivity is detected. The adrenal medulla is formed by immature neuroblasts (CgA -, NCAM+) which migrate and proliferate from the periphery toward the center of the gland, where they differentiate in mature neuroblasts (CgA+). In the two cases of congenital adrenal hypoplasia of anencephalic type without DAX 1 and SF-1 mutation, the cause is probably from pituitary origin and related to absence of gonadotrope cells. In the third case of congenital adrenal hypoplasia, never described, combining a retard intrauterine development, a congenital adrenal hypoplasia, sexual ambiguity, pituitary abnormalities. The absence of mutation of known genes (DAX -1, SF -1, SRY, FGF9, SOX2, SOX3, SOX5 and SOX9) suggests the existence of new genes regulating early differentiation of the adrenal, the gonad and the pituitary., L’embryologie de la surrénale humaine et la pathogénie de l’hypoplasie congénitale des surrénales sont mal connues et complexes. L’une pouvant expliquer l’autre, nous présentons, à partir de 119 fœtus humains normaux de12 à 36 semaines de développement (SD), une étude cinétique histologique et moléculaire de la surrénale fœtale et nous décrivons 3 cas d’hypoplasie surrénalienne. Après un rappel des mécanismes moléculaires connus, régulant ensemble l’embryologie surrénalienne, gonadique et hypophysaire et ceux de l’hypoplasie surrénale congénitale, nous présentons nos résultats. Dans la corticosurrénale humaine fœtale normale, les cellules du cortex permanent prolifèrent et, dès la 12ème SD, expriment la NCAM, la 3β-HSD et la P450 c21. Elles ont la capacité de synthétiser des minéralocorticoïdes et/ou du cortisol. Les cellules du cortex fœtal ne prolifèrent pas et expriment ni la 3β-HSD, ni la NCAM. La médullosurrénale est formée par des neuroblastes immatures (CgA-, NCAM+) qui migrent et prolifèrent de la périphérie vers le centre de la glande, où ils se différencient en neuroblastes matures (CgA+). Dans les deux cas d’hypoplasie surrénale de type anencéphalique, avec absence de mutation de DAX-1 et de SF-1, la dysembryoplasie surrénalienne est probablement d’origine hypophysaire, par absence de cellules gonadotropes. Dans le 3ème cas, jamais décrit, associant un RCIU, une hypoplasie surrénalienne congénitale, une ambiguïté sexuelle, une absence de différenciation des cellules antéhypophysaires, l’absence de mutation de gènes connus (DAX-1, SF-1, SRY, FGF9, SOX2, SOX3, SOX5 et SOX9) suggère l’existence de nouveaux gènes régulant la différenciation précoce de ces trois glandes endocrines.

Diplôme : Dr. d'Université

The embryology of the human adrenal and the pathogenesis of the hypoplasia adrenal congenital are complex and not well known. We studied the histological and functional characteristics of the fetal human adrenal in normal fetuses aged 12 to 36 weeks development (WD) and presented three cases of congenital adrenal hypoplasia with pituitary abnormalities. In the human fetal adrenal cortex, only the cells of the definitive zone proliferate from the 12th WD. We observe the expression of an adherence protein (NCAM) and of two steroidogenesis enzymes (3β-HSD and P450 c21) in the definitive zone cells, attesting to the capacity of these cells to synthesize mineralocorticoids and/or cortisol. In the fetal zone, only P450 c21 immunoreactivity is detected. The adrenal medulla is formed by immature neuroblasts (CgA -, NCAM+) which migrate and proliferate from the periphery toward the center of the gland, where they differentiate in mature neuroblasts (CgA+). In the two cases of congenital adrenal hypoplasia of anencephalic type without DAX 1 and SF-1 mutation, the cause is probably from pituitary origin and related to absence of gonadotrope cells. In the third case of congenital adrenal hypoplasia, never described, combining a retard intrauterine development, a congenital adrenal hypoplasia, sexual ambiguity, pituitary abnormalities. The absence of mutation of known genes (DAX -1, SF -1, SRY, FGF9, SOX2, SOX3, SOX5 and SOX9) suggests the existence of new genes regulating early differentiation of the adrenal, the gonad and the pituitary., L’embryologie de la surrénale humaine et la pathogénie de l’hypoplasie congénitale des surrénales sont mal connues et complexes. L’une pouvant expliquer l’autre, nous présentons, à partir de 119 fœtus humains normaux de12 à 36 semaines de développement (SD), une étude cinétique histologique et moléculaire de la surrénale fœtale et nous décrivons 3 cas d’hypoplasie surrénalienne. Après un rappel des mécanismes moléculaires connus, régulant ensemble l’embryologie surrénalienne, gonadique et hypophysaire et ceux de l’hypoplasie surrénale congénitale, nous présentons nos résultats. Dans la corticosurrénale humaine fœtale normale, les cellules du cortex permanent prolifèrent et, dès la 12ème SD, expriment la NCAM, la 3β-HSD et la P450 c21. Elles ont la capacité de synthétiser des minéralocorticoïdes et/ou du cortisol. Les cellules du cortex fœtal ne prolifèrent pas et expriment ni la 3β-HSD, ni la NCAM. La médullosurrénale est formée par des neuroblastes immatures (CgA-, NCAM+) qui migrent et prolifèrent de la périphérie vers le centre de la glande, où ils se différencient en neuroblastes matures (CgA+). Dans les deux cas d’hypoplasie surrénale de type anencéphalique, avec absence de mutation de DAX-1 et de SF-1, la dysembryoplasie surrénalienne est probablement d’origine hypophysaire, par absence de cellules gonadotropes. Dans le 3ème cas, jamais décrit, associant un RCIU, une hypoplasie surrénalienne congénitale, une ambiguïté sexuelle, une absence de différenciation des cellules antéhypophysaires, l’absence de mutation de gènes connus (DAX-1, SF-1, SRY, FGF9, SOX2, SOX3, SOX5 et SOX9) suggère l’existence de nouveaux gènes régulant la différenciation précoce de ces trois glandes endocrines.

International audience; Environmental exposure to endocrine disrupting compounds (EDCs) during development could adversely affect reproductive function via effects on the hypothalamo-pituitary-gonadal axis (HPG). The HPG axis is regulated by many steroid sensitive inputs, including the KiSS-1 gene product kisspeptin. We have previously shown that KiSS-1 mRNA and protein are expressed within gonadotrophs in the foetal ovine pituitary and that KiSS-1 mRNA expression is decreased following gestational exposure to EDCs. The current study aimed to determine whether KiSS-1 mRNA expression is also changed in pituitary glands of adult animals exposed to EDCs in-utero. Tissue was obtained from 12 month old male and female sheep born to mothers pastured on fields fertilised with inorganic fertiliser (C) or sewage sludge (T) throughout pregnancy (n=12 per group). mRNA was extracted, reverse transcribed and KiSS-1 mRNA expression quantified by QrtPCR (relative to β-actin). Data were analysed using two-way ANOVA. Results - KiSS-1 mRNA expression was significantly (P

Background: Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to “real-life,” environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal.\ud Objectives: We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein–coupled receptor 54) system.\ud Methods: KiSS-1, GPR54, and ERα (estrogen receptor α) mRNA expression was quantified in control (C) and treated (T) maternal and fetal (110-day) hypothalami and pituitary glands using semiquantitative reverse transcription polymerase chain reaction, and colocalization of kisspeptin with LHβ (luteinizing hormone β) and ERα in C and T fetal pituitary glands quantified using dual-labeling immunohistochemistry.\ud Results: Fetuses exposed in utero to the EDC mixture showed reduced KiSS-1 mRNA expression across three hypothalamic regions examined (rostral, mid, and caudal) and had fewer kisspetin immunopositive cells colocalized with both LHβ and ERα in the pituitary gland. In contrast, treatment had no effect on parameters measured in the adult ewe hypothalamus or pituitary.\ud Conclusions: This study demonstrates that the developing fetus is sensitive to real-world mixtures of environmental chemicals, which cause significant neuroendocrine alterations. The important role of kisspeptin/GPR54 in regulating puberty and adult reproduction means that in utero disruption of this system is likely to have long-term consequences in adulthood and represents a novel, additional pathway through which environmental chemicals perturb human reproduction.

Diplôme : Dr. d'Université

International audience

Leptin is an adipose hormone implicated in the control of energetic balance and growth hormone (GH) secretion. Its receptors ObRa and ObRb are expressed in the rat somatotroph cells and leptin regulates ghrelin receptor expression in the pituitary. In our obese DIO rats model, the alteration of plasma GH levels, identified in this pathology, is not related to pituitary resistance to leptin. In the Lou/C rats, GH is involved in the resistance to obesity, with leptin and ghrelin hormones playing a major role in the pituitary control of its secretion. In vitro, ObRb internalisation is constitutive but leptin inhibits the traffic of this receptor from the Golgi apparatus to the plasma membrane. This internalisation is required for STAT3 activation and thus this cellular process could be involved in leptin resistance development., La leptine est une hormone adipocytaire impliquée notamment dans le contrôle de la balance énergétique et de la sécrétion d'hormone de croissance (GH). Ses récepteurs ObRa et ObRb sont exprimés dans les cellules somatotropes de rat, et elle régule l'expression hypophysaire du récepteur de la ghréline. Dans notre modèle de rats obèses DIO, l'altération des taux plasmatiques de GH caractéristique de cette pathologie n'est pas liée à la résistance hypophysaire à la leptine. Chez les rats Lou/C, la GH participe à la résistance à l'obésité, les hormones ghréline et leptine jouant un rôle prépondérant dans le contrôle hypophysaire de sa sécrétion. In vitro, l'internalisation de ObRb est constitutive mais la leptine inhibe l'adressage de ce récepteur de l'appareil de Golgi vers la membrane plasmique. Cette internalisation est indispensable pour l'activation de STAT3 et ce processus pourrait donc participer à l'établissement de la résistance à la leptine.

Soutenue le 12 juillet 2006 Diplôme : Dr. d'Universite

International audience

Cet article fait partie du dossier : L’augmentation de la prolificité des truies : acquis, progrès envisageables et conséquences; National audience

National audience

Fatty acid composition of anterior pituitary cell membranes of rats deprived of essential fatty acids (EFA) and of rats receiving a standard diet was determined during postnatal development and in adults. Pregnant rats were fed an EFA-deficient diet and the offspring were fed the same diet after weaning. In parallel, effects of the diet on growth and on growth hormone (GH) responsiveness to GHRH stimulation were determined in control animals. Membrane content of arachidonic acid (20:4n-6) and of its elongation product adrenic acid (22:4n-6) increased regularly from day 2 to day 12 after birth. EFA-deficiency resulted on day 2 in increased oleic acid and in substitution of arachidonic and adrenic acids by corresponding elongation-desaturation products of oleic acid: eicosatrienoic (20:3n-9) and docosatrienoic (22:3n-9) acids. At the age of 24 days, n-9 series fatty acid reached the same level as in adult animals. Two-day-old EFA-deficient rats paradoxically exhibited a higher level of 20:4n-6 as compared to control rats. EFA-deficiency also decreased growth rate and GH pituitary responses to GHRH during the prepubertal period. These results suggest that changes in the lipid structure and in pituitary secretion properties elicited by EFA-deficiency depend upon the stage of development.

International audience; The aim of the present paper was to obtain somatotroph- and gonadotroph-enriched populations from collagenase dispersed pituitaries of male rainbow trout. Inasmuch as the percentage of immunoreactive gonadotrophs and somatotrophs present in pituitaries was higher at spermiation than at the beginning of spermatogenesis, we tried such a cell separation with fish at this stage of spermatogenesis. Cells were fractionated using their differences in buoyant density with centrifugation in Percoll solutions. The use of Percoll linear gradients (1.110 to 1.027 g/ml) showed that somatotroph cells have a density of between 1.102 and 1.064 g/ml whereas gonadotrophs are spread over the range of the gradient. It was thus possible, by using linear or discontinuous Percoll gradients, to obtain 95 to 67% (mean 80%) enriched somatotropic cell fractions while no enriched gonadotropic cell fractions were collected. The fractionated cells kept their ability to be cultured and to be responsive to specific secretagogues. Somatostatine induced a 80 to 85% decrease in growth hormone release per somatotroph in the initial cell suspension as well as in the different cell fractions. On the other hand, the basal growth hormone release per cell was lower in the fractions containing cells with a density lower than 1.062 g/ml. Inversely, the gonadotrophs have a basal release per cell independent of their density, and this is also available for their responsiveness to salmon gonadotropin-releasing hormone.

International audience; We report here that cytochrome P4501A1 in the male rainbow trout pituitary is highly inducible by beta-naphthoflavone. Pituitary cells containing inducible P4501A1 were identified by double immunostaining as gonadotrophs containing gonadotropin II. Thus, the pituitary gonadotrophs may be target cells for polyaromatic hydrocarbons. Elevated plasma levels of gonadotropin II (GTH II) and testosterone in the induced fish indicated that the functioning of the pituitary was disturbed. Because GTH II regulate the final stage of sexual maturation the results implies that exposure to P4501A1 inducing compounds may disturb this development stage.

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National audience

To study the control of prolactin secretion in fish, an in-vitro technique using a monolayer cell culture system of rainbow trout pituitary glands was developed. Such secretion was characterized by measurement of both prolactin release and prolactin mRNA content using a trout prolactin cDNA as a probe. This cell culture technique, already used to study the regulation of gonadotrophin secretion in rainbow trout, was further validated by measuring total DNA and protein content. Both parameters appeared to be stable after 2 days of culture. Studying the effect of somatostatin (SRIF) on prolactin cells indicated that a maximal inhibitory effect (62%) was observed after 24 h of treatment. Significant inhibition of prolactin release was obtained for SRIF doses ranging from 50 nm to 1 μm. However, in the same experiment, SRIF was much more potent as an inhibitor of growth hormone release. Short-term (

International audience; A recombinant human IGF-I (rhIGF-I) was applied to primary cultures of rainbow trout pituitary cells. In wells containing 3 x 10(4) and 6 x 10(4) cells/well, rhIGF-I inhibited basal GH release both in short (6 h) and long (12 and 24 h) exposures. The decline in GH release was dose-dependent over the range of 0.01 and 100 mM. The combination of rhIGF-I and low concentrations of synthetic somatostatin 14 (SRIF) enhanced the inhibitory effect of rhIGF-I in an additive manner. Any appreciable effect of rhIGF-I on PRL release was not evidenced. To our knowledge, this report demonstrates for the first time the participation of IGFs on the inhibitory component of fish GH regulation.

Using a specific antiserum raised against synthetic neuropeptide-Y (NPY), the distribution of NPY-like immunoreactivity in the brain and pituitary of the trout Oncorhynchus mykiss has been examined with the indirect immunofluorescence and peroxidase-antiperoxidase methods. The highest density of NPY-immunoreactive elements was found in the basal telencephalon and hypothalamus. In particular, NPY-immunoreactive neurons were located in the nucleus entopeduncularis and the preoptic nucleus. NPY-immunoreactive fibers were observed throughout the trout brain. The preoptic nucleus, the suprachiasmatic nucleus, and the nucleus entopeduncularis were densely innervated. In addition, NPY-positive fibers were detected in the nucleus lateralis tuberis and in the distal and intermediate lobes of the pituitary. The NPY-like peptide of the trout brain was characterized by combining HPLC analysis and radioimmunological detection. Serial dilutions of trout hypothalamus and pituitary extracts produced displacement curves that were parallel to the standard curve. HPLC analysis resolved a major peak which was slightly less hydrophobic than porcine NPY. The possible effect of NPY, either alone or in combination with a GnRH antagonist, on gonadotropin (GtH) release from trout pituitaries was investigated using a perifusion system technique. Graded concentrations of synthetic NPY induced a dose-dependent stimulation of GtH release. The stimulatory activities of NPY and various short chain analogs on GtH release were compared: the order of potency was NPY greater than NPY-(2-36) greater than NPY-(16-36) greater than NPY-(25-36). This result suggests that the biological determinant of NPY is located in the C-terminal part of the molecule. Administration of a short pulse of NPY or GnRH (10(-7) M each) induced a marked stimulation of GtH release. Prolonged infusion of the GnRH antagonist D-Phe2-6,Pro3-GnRH induced a significant reduction of GnRH-evoked GtH secretion. In addition, the GnRH antagonist blocked NPY-induced GtH release. The widespread distribution of NPY in the trout brain suggests the involvement of this neuropeptide in a variety of physiological functions. The present data support the view that NPY, released by nerve terminals in the distal lobe of the pituitary, may act presynaptically on GnRH fibers to modulate GtH release.

International audience; In rainbow trout, a variable in vivo pituitary sensitivity to GnRH has been previously observed, depending on the stage of oogenesis. The purpose of the present work was to study, in vitro, the role of oestradiol (E2) and 17α-hydroxy,20β-dihydroprogesterone (17α20βP), respectively, involved in vitellogenesis and in oocyte maturation, upon this variability. The study was performed using primary cultures of whole pituitary cells from animals at different stages of oogenesis and subjected to increasing doses of salmon GnRH (sGnRH) after a 3-day pretreatment with control medium or medium supplemented with the steroid at levels corresponding to those circulating at the time of particular events of the sexual cycle (maturation and vitellogenesis). In control cultures, pituitary GtH responsiveness to sGnRH was maximal at ovulation, since at this time the gonadotrophs were able to respond to 10−9 M sGnRH, whereas during vitellogenesis and preovulatory stages, the minimal effective dose of sGnRH ranged between 10−6 and −8 M. We have demonstrated that 17α20βP has a positive or negative effect by acting directly on pituitary cell responsiveness to sGnRH, depending on the stages at which it is applied; its effect is positive during early vitellogenic and preovulatory stages whereas it is negative at the time of ovulation. E2 also increased pituitary responsiveness to sGnRH when applied during early vitellogenesis at low doses, corresponding to circulating levels at the time of ovulation; higher levels of E2, corresponding to circulating levels found during the last stages of vitellogenesis, did not modify pituitary responsiveness but increased cell GtH content. Results obtained are discussed in relation to hormonal changes (gonadotropin and steroid hormones) observed by different authors during the sexual cycle.

The lactogenic properties of extracts of the pituitary glands of salmon and trout were evaluated by using the organ culture technique with rabbit mammary explants. Crude extracts and fractions obtained after chromatography on Ultrogel and selected for their capacity to compete with ovine prolactin in a rabbit mammary gland radioreceptor assay were added to the culture medium. The criteria of lactogenesis were lactose synthetase activity, casein synthesis, measurements of the concentration of casein messenger RNA and the histology of mammary glands. All these tests led to the conclusion that salmon and trout pituitary glands contain a prolactin-like principle capable of initiating milk synthesis in the rabbit mammary cell.

Le cycle reproducteur des poissons est sous la dépendance de l'hypophyse qui élabore et secrète les hormones gonadotropes. Ces hormones interviennent lors du déroulement de la gamétogenèse et sont produites activement pendant la maturation ovocytaire puis l'ovulation. La technique d'induction de ponte dite technique d'hypophysation consiste en un apport exogène d'hormone gonadotrope par injection d'hypophyses pour provoquer le déroulement de phases du cycle sexuel qui ne se produisent pas spontanément en condition de captivité comme l'ovulation.

International audience; To study the regulation of gonadotropin secretion in rainbow trout in vitro, a method for preparing primary cultures of dispersed pituitary cells is described. Cells were dispersed by collagenase 0.1% in Hank's saline solution for 20 hr at 12 degrees and a high yield of viable cells was obtained. Attempts to improve cell functioning were made by varying culture conditions (density of cells initially plated, age of the culture). Cell functioning was assessed by their ability to respond to increasing doses of mammalian and salmon GnRH. Pituitaries were collected from spermiating males whose pituitaries are known to be sensitive to mammalian GnRH in vivo. Using 96-well plates, optimal conditions for good biological activity, are initial plating with 6.2 X 10(4) cells, incubation with GnRH for 24 hr on the third day after plating. In these conditions mammalian analog and salmon GnRH induced an increase in GtH release for doses ranging from 10(-9) to 10(-6) M. The GtH released during the GnRH incubation period does not decrease the sensitivity of the system since addition of 20 ng of GtH at the beginning of incubation does not modify the response profile.

International audience; The effect of implanting an extra pituitary containing large amounts of gonadotropic hormone (GtH), combined or not with a luteinizing hormone releasing-hormone analogue (LHRHa) treatment, on GtH levels and gonadal development was investigated in juvenile host fish. The extrapituitaries were collected from mature spermiating fish or from immature fish treated with testosterone. In recipient males and females circulating plasma GtH levels increased following transplantation of both types of pituitaries. Elevated GtH levels presumably triggered steroid synthesis by the immature male gonad since pituitary GtH content was observed to accumulate in recipient males and not in females. However, the potency of the two kinds of pituitaries seemed different since spermatogenesis was stimulated only in some recipient males bearing a mature adult pituitary. This divergence could be due to a different sensitivity to endogenous gonadotropin-releasing hormone (GnRH). Only mature extrapituitaries might be highly sensitive to GnRH, as suggested by results obtained in juvenile host fish after LHRHa treatment. At the end of the 6-week experimental period, this LHRHa treatment stimulated spermatogenesis and induced a significant increase in pituitary GtH content only in juvenile hosts transplanted with a mature pituitary. Such a result was not observed in juvenile hosts submitted to a LHRHa treatment combined or not with the transplantation of juvenile testosterone-treated pituitary. However, previous works have shown that pituitaries collected from immature testosterone-treated fish are sensitive to GnRH. In the present experiment, the amount of GnRH-induced GtH release might have been too low to initiate spermatogenesis during the 6-week experimental period.

Reproductive physiology in cichlid fishes, with particular reference to Tilapia and Sarotherodon

Séance du 27 mai 1979 à Brest; Using radioimmunoassays, plasma levels of carp gonadotropin (c-GTH) and oestradiol-17beta (E2) are measured every day in Carp, during induced spawning (water temperature = 15 °C). Ten Carps injected twice intraperitonealy with a total extract of Carp hypophysis (0,6 mg/kg BW at J0 and 5,4 mg/kg BW at J1) are compared to a lot receiving only saline solution. No evolution is detected in that last group when in the experimental one E2 level increases with exogenous c-GTH (see table). Even if E2 levels are low at the end of vitellogenesis, steroidogenic structures remain sensitive to an exogenous hypophysial stimulation. Secretion ability differs within individuals correlation coefficient between total estimated c-GTH and E2 = 0,15).

International audience; In fish there are few data on the gonadotropin-releasing hormone (Gn-RH) neurosecretory activity, which could explain long- and short-term variations of the gonadotropin secretion. There is no biological species specificity between mammal and fish Gn-RH; although there is a structural difference, they are, on the contrary, characterized by a high immunological specificity which does not allow measurement of fish Gn-RH using radioimmunoassay for LH-RH. We have synthesized salmon Gn-RH according to the formula recently proposed by Sherwood (N. Sherwood, L. Eiden, M. Brownstein, J. Spies, J. Rivier, and W. Vale, 1983. Proc. Natl. Acad. Sci. USA 80, 2794-2798). Its activity has been tested by its ability to stimulate the gonadotropin hormone (GtH) secretion in vivo in testosterone-implanted juvenile rainbow trout, and for the recognition of synthesized Gn-RH (s-Gn-RH) perykaria by a specific antibody raised against the s-Gn-RH in regions of the brain described as containing LH-RH immunoreactive-like material. A radioimmunoassay has been developed for the salmon Gn-RH, and its specificity to measure trout Gn-RH has been tested. Using this assay, the brain and pituitary Gn-RH contents have been measured throughout the final phases of maturation and ovulation. Brain Gn-RH increases from the end of vitellogenesis (8.9 +/- 0.76 ng/brain) to ovulation (more than 15 ng/brain). Pituitary Gn-RH is lower (1.58 +/- 0.69 ng/pituitary) at the end of vitellogenesis and follows a similar profile as in the brain, except for a significant decrease just prior the beginning of oocyte maturation. The correlations between Gn-RH levels and GtH pituitary and plasma levels show that total brain Gn-RH is never correlated to the GtH, suggesting that the increase in the brain Gn-RH content is related to a Gn-RH system closely related to maturation and ovulation, which remains to be investigated. On the contrary, pituitary Gn-RH levels are well correlated with pituitary and plasma GtH levels, indicating that pituitary Gn-RH levels might represent a good index of the Gn-RH neurosecretory activity in the fish hypothalamohypophysial complex, given the absence of a portal system in teleost.

National audience

International audience; Le méthallibure administré en bains à la dose de 2 p.p.m. entraîne chez le poisson rouge (Carassius auratus) une inhibition de la spermatogenèse qui intéresse toutes les cellules germinales à l'exception des spermatogonies A. Lorsque les mâles soumis à ce traitement reçoivent en même temps des injections de poudre hypophysaire brute de Carpe, la spermatogenèse est maintenue et même fortement stimulée. Après la suppression du traitement au méthallibure, la spermatogenèse se rétablit complètement en 20 jours, mais la restauration est plus importante si les animaux reçoivent des injections de poudre hypophysaire brute de Carpe.

Des extraits hypothalamiques de Carpe ou de Truite stimulent la sécrétion in vitro de LH par des hypophyses de Bélier. lnversement des extraits hypothalamiques de Bélier stimulent la sécrétion de c-HG par des hypophyses de Carpe. Ce résultat permet d'étendre aux Poissons la non spécificité des hormones hypothalamiques gonadotropes déjà montrée in vivo et in vitro à l'intérieur de la classe des mammifères, et entre les mammifères et les oiseaux

Testosterone : effects on the maintenance of spermatogenesis in intact and hypophysectomized goldfish (Carassius auratus)

International audience; Il existe une confusion importante dans la notion de spécificité d’action des hormones gonadotropes de Poissons. Cette notion a été précisée en utilisant deux méthodes différentes : d’une part la comparaison des activités biologiques de différents extraits hypophysaires de Poissonssur un même récepteur testiculaire, d’autre part la détermination de leur comportement immunologique vis-à-vis d’anticorps hautement spécifiques dirigés contre l’hormone gonadotrope de Carpe c-HG et o-LH. La spermatogenèse du Carassin, Carassius auratus et du Guppy, Poecilia reticutata hypophysectomisés ne peut être regénérée quantitativement qu’avec des hormones gonadotropes ou extraits hypophysaires autologues d’une espèce donneuse très proche de l’espèce receveuse. La technique de compétition isotopique vis-à-vis d’anticorps spécifiques d’une entité moléculaire définie, donne des résultats comparables. Seuls des extraits hypophysaires de Carpe et d’autres Cyprinidés peuvent déplacer de l’hormone de Carpe marquée à l’iode 131 I (c-HGI 131) du complexe c-HGI131, anti c-HG. Les hormones mammaliennes o-LH, o-FSH et HCG n’ont en aucun cas montré d’activité sur la spermatogenèse du Carassin et du Guppy ni d’affinité vis-à-vis d’anticorps dirigés spécifiquement contre une hormone gonadotrope de Poisson. Ces résultats confirment l’existence d’une spécificité zoologique d’action des hormones gonadotropes hypophysaires entre les Mammifères et les poissons teléostéens et à l'intérieur même des différentes familles de téléostéens