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Le traitement par hormone de croissance concerne des milliers de jeunes en France, atteints de pathologies diverses, entrant dans le cadre des maladies chroniques. L’adhérence chez ces patients est une des préoccupations des pédiatres, dans la mesure où cela impacte les résultats du traitement, notamment sur le gain de taille. Un facteur peu étudié dans cette population mais pressenti comme impactant l’adhérence est la décision médicale partagée, qui se définit comme une relation de soin dans laquelle le patient et le médecin collabore pour déterminer la meilleure option de traitement. L’objectif de l’étude est d’explorer la vision des médecins concernant la participation au projet de soin de l’adolescent traité par hormone de croissance au long cours.Méthode : dans cette étude qualitative exploratoire, des pédiatres spécialisés en Endocrinologie, ayant au moins 5 ans d’expérience avec les patients traités par hormone de croissance, ont été recrutés sur la base du volontariat. Des focus groups ont été menés et transcrits, puis codés au moyen d’une analyse thématique, alliant une approche déductive et inductive, par une des investigatrices et relus par un autre investigateur, ayant une expérience significative dans ce type d’analyses.Résultats : 15 pédiatres issus de 4 centres hospitalo-universitaires différents ont été interrogés lors de 3 focus groups. La motivation dans le traitement semble influencée par les bénéfices attendus et perçus par le jeune, ainsi que par les contraintes perçues du traitement. Les compétences de l’adolescent, englobant ses connaissances sur sa maladie et sur son traitement, ainsi que sa capacité d’auto normativité, vont impacter ses attentes et sa participation à son projet de soin. Les parents sont également partie prenante de ce projet, tant au moment de la décision que sur la pérennisation du traitement. Au long cours, les besoins du jeune varient, allant de la volonté de faire le point sur le traitement à la demande d’arrêt de celui-ci. Enfin, l’établissement d’une relation de confiance entre le médecin et l’adolescent, avec une écoute attentive de la part du médecin, est essentiel.Discussion : le replacement de l’adolescent dans la décision semble la clé menant à sa participation à son projet de soin. Plusieurs stratégies d’implications ont été mises en évidence (faire le point régulièrement sur l’histoire médicale et les bénéfices du traitement, implication dans le choix du dispositif d’injection, compétences relationnelles du médecin pour une meilleure écoute des besoins du jeune). Un biais cognitif est cependant probable et de futures études sont nécessaires pour recueillir la vision des adolescents et de leurs parents.Conclusion : la décision médicale partagée chez l’adolescent traité par hormone de croissance au long cours repose sur un ensemble de facteurs interconnectés (place des parents, attitude du médecin et place laissée et prise par l’adolescent dans la décision). Plusieurs stratégies d’implication de l’adolescent ont été mises en évidence, ouvrant la voie à des pistes pour l’amélioration des pratiques dans la prise en charge de ces patients.

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.

Introduction: Larsen syndrome of Reunion Island is a rare skeletal dysplasia. Patients suffer from facial dysmorphia, articular dislocations and a severe retarded physical development. It is caused by a homozygous mutation in the ß4GALT7 gene. The growth of these patients still needs to be better understood. This study aims to analyse the physical development of Larsen syndrom patients based on the largest group possible, as well as evaluate their response and tolerance to growth hormone treatment.Method: It is an observational retrospective cohort study and monocentric on 37 patients in Reunion, from 1927 to 2020. Inclusion criteria are both clinical and genetic. Results: 37 patients were considered. The average adult size is 127.1 cm (-8 DS) +/- 10.4 (literally 114-139 [-10 to -6 DS]) and 120.6 cm (-7,5 DS) +/- 7.6 (literally 110-134.5 [-9.5 à -5 DS]) respectively, for men (n=4) and women (n=8). With hormone growth treatment, the average adult size is 137.4 cm (-6 DS) +/- 10.1 (literally 121-146 [-9 to -4,5 DS]) and 125 cm (-7 DS) +/- 14 (literally 101-135 [-11 to -5 DS]) respectively, for men (n=5) and women (n=5). From a clinical point of view, one girl had worsened scoliosis, but also progressed after stopping growth hormone treatment. From a biological point of view, two patients have developed type 2 diabetes after stopping growth hormone treatment.Conclusion: Larsen syndrome of Reunion Island patients suffer from a severe retarded physical development, that should benefit from endocrinological exploration. Growth hormone treatment may be discussed with the child and family in order to improve adult size prognosis and body composition.; Introduction : Le Syndrome de Larsen de La Réunion est une dysplasie squelettique rare, endémique de l’île. Les patients ont une dysmorphie faciale, des luxations articulaires par hyperlaxité ligamentaire et un retard statural sévère. Il est dû à une mutation homozygote du gène ß4GALT7. La croissance de ces patients est mal connue. L’objectif de cette étude est d’analyser la croissance staturale de la plus grande cohorte de Larsen de La Réunion, ainsi que d’évaluer le traitement par hormone de croissance et la tolérance. Méthode : Il s’agit d’une étude de cohorte observationnelle, rétrospective et monocentrique sur l’île de La Réunion, de 1927 à 2020. Les critères d’inclusion sont cliniques et génétiques. Résultats : 37 patients ont été inclus. La taille moyenne adulte est de 127,1 cm (-8 DS) +/- 10,4 (114-139 soit -10 à -6 DS) et de 120,6 cm (-7,5 DS) +/- 7,6 (110-134,5 soit -9,5 à -5 DS) respectivement pour les hommes (n=4) et les femmes (n=8). Sous hormone de croissance, elle est de 137,4 cm (-6 DS) +/- 10,1 (121-146 soit -9 à -4,5 DS) et 125 cm (-7 DS) +/- 14 (101-135 soit -11 à -5 DS) respectivement pour les hommes (n=5) et les femmes (n=5). Sur le plan clinique, une fille a eu une aggravation de scoliose qui a continué à progresser après l’arrêt du traitement. Sur le plan biologique, deux ont développé un diabète de type 2 post arrêt du traitement. Conclusion : Les patients Larsen de La Réunion présentent un retard statural sévère qui doit bénéficier d’une exploration endocrinologique. Un traitement par hormone de croissance peut être discuté avec la famille et l’enfant pour améliorer le pronostic de taille finale et la composition corporelle.

La croissance résulte d’un ensemble de phénomènes complexes sous l’influence de multiples facteurs : génétiques, métaboliques, environnementaux et surtout hormonaux. Son suivi doit être effectué de manière régulière tout au long du développement de l’enfant. On parle de retard de croissance staturale lorsque la taille de l’enfant est inférieure à moins 2 déviations standards par rapport aux courbes de croissance de référence. S’il existe également un ralentissement de la vitesse de croissance, il convient d’effectuer une exploration de ce retard, par un pédiatre endocrinologue, afin d’en rechercher la cause. Le plus souvent les examens effectués ne permettent pas d’en déterminer l’origine sauf dans certaines situations cliniques bien précises. La petite taille peut ainsi provenir d’un déficit en hormone de croissance ou être secondaire à de multiples pathologies. Un traitement par hormone de croissance recombinante peut alors être administré quotidiennement à l’enfant lorsqu’un certain nombre de critères sont remplis. L’efficacité de cette thérapeutique repose principalement sur sa régularité : l’acceptation et la compréhension par les jeunes patients et leurs parents est donc indispensable. Les ateliers d’éducation thérapeutique proposés par les services d’endocrinologie pédiatrique s’inscrivent dans cette démarche mais également le pharmacien d’officine via son rôle de conseil qu’il accomplit lors des dispensations mensuelles du traitement. En effet ces échanges réguliers sont propices à l’instauration d’un dialogue et d’une relation de confiance avec l’enfant et sa famille permettant d’appréhender l’observance du traitement et d’en éviter l’interruption.

International audience; Aim: Growth hormone (GH) deficiency is associated with increased cardiovascular mortality. Insulin resistant states and lipid profile alterations with hypertriglyceridemia, decreased HDL cholesterol, increased small and dense LDL and postprandial hyperlipidemia are commonly observed in GH deficient patients but GH specific function in triglyceride-rich lipoprotein (TRL) metabolism regulation remains unclear. Methods: Lipids and apolipoproteins (apo) profiles were investigated in fasting and postprandial states in plasma and TRL fractions during a test meal before (M0) and after one month of discontinued GH treatment (M1) in GH deficient patients (n=10). Results: After one month of discontinued GH treatment, GH levels remained unchanged but IGF-1 decreased significantly (-12,12±2,36nmol/L). We observed a significant weight loss (-1,31±0,45kg) together with body composition significant changes : lean mass decrease and fat mass increase (-1,17±0,41kg and +0,36±0,16kg respectively), and insulin resistance parameters modifications with a significant HOMA-index reduction (-0,45±0,19) associated with both significant decreased fasting insulin and C-peptide (-2,04±0,78Mui/L and -0,15±0,05nmol/L respectively) but fasting plasma glucose remained unchanged. Fasting plasma triglycerides and apoC-III levels decreased significantly (-0,41±0,16mmol/L and -23,07±6,93mg/L respectively), main other fasting lipid parameters assessed in the plasma fraction (total, LDL and HDL cholesterol, but also apoA1, apoB, apoB48 and apoC-II) were unchanged. Triglycerides but also apoC-II and apoC-III levels assessed in TRL fraction decreased significantly both in fasting and postprandial states after GH discontinuation. Conclusions: Lipid profiles alterations both in fasting and postprandial states were observed in GH deficient patients after GH treatment discontinuation suggesting a specific role of GH in TRL metabolism specifically altered in this pathology.

Introduction : Bien que de nombreuses études aient démontré l’efficacité d’un traitement par hormone de croissance recombinante (rGH) chez les enfants nés petits pour l’âge gestationnel (SGA), il existe une grande variabilité dans la réponse entre les patients. Plusieurs facteurs prédictifs de réponse à la rGH ont déjà été décrits dans la littérature tels que l’âge au début du traitement, la dose de rGH ou encore la taille cible parentale. Mais peu de données existent concernant la valeur prédictive des données préthérapeutiques sur la réponse à la rGH. Matériel et Méthodes : L’objectif principal de l’étude est d’identifier les facteurs prédictifs de la réponse à la rGH chez les enfants nés SGA, avec un intérêt particulier pour les données cliniques et biologiques avant l’initiation du traitement et notamment l’évolution pondérale au cours des premières années de vie. Il s’agit d’une étude monocentrique, restrospective réalisée au CHU de Nancy. La réponse à la rGH est définie par la variation de déviation standard (DS) pour la taille après 1, 2 ans de traitement, à l’arrêt du traitement et à la taille finale adulte. Des analyses de régression uni et bivariées sont réalisées. Résultats : 108 enfants nés SGA ont été traités par rGH à Nancy, 91 patients ont été inclus. A 2 ans de traitement, la réponse à la rGH est positivement corrélée au taux de TSH préthérapeutique (r =1,1 ; p = 0,0204) en analyse multivariée et en analyse bivariée (r =0,09 ; p = 0,0449). La réponse à la rGH une fois la taille finale atteinte est significativement positivement associée au taux de cholestérol préthérapeutique (r = 1,64 ; p = 0,0341) et négativement associée au taux de cortisol préthérapeutique (r = -0,02 ; p = 0,0217) et au taux de T4 (r = -0,31 ; p = 0,0417) en analyse bivariée. Aucune association significative n’est mise en évidence avec l’évolution pondérale au cours des premières années de vie. Discussion : Cette étude met en avant le rôle du fonctionnement thyroïdien, surrénalien et métabolique dans la réponse à la rGH chez les enfants nés SGA via un possible mécanisme de programmation foetale.

Although homo- or heterodimerization are common mechanisms for activation of cytokine receptors, cross-talk between two distinct receptors in this superfamily has been never shown. Here we show a physiologically relevant example indicating that such an interaction does occurs, thus raising the hypothesis that heterodimerization between distinct cytokine receptors may be a novel mechanism contributing to the diversity of cytokine signaling. These findings were documented using both surface plasmon resonance and gel filtration experiments and show that ovine placental lactogen (PL) heterodimerizes the extracellular domains (ECDs) of ruminant growth hormone receptor (GHR) and prolactin receptor (PRLR). We also show that PL or PL analogues that exhibit little or no activity in cells transfected with PRLRs and no activity in cells transfected with ovine GHRs exhibit largely enhanced activity in cells cotransfected with both PRLRs and GHRs. Furthermore, chimeric receptors consisting of cytosolic and transmembrane part of ovine GHR or ovine PRLR and ECDs of human granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha or beta were constructed. Upon transfection into Chinese hamster ovary cells along with reporter luciferase gene and stimulation by GM-CSF, a significant increase in luciferase activity occurred when GM-CSFR-alpha-PRLR and GM-CSFR-beta-GHR or GM-CSFR-alpha-GHR and GM-CSRR-beta-PRLR were cotransfected. In conclusion, we show that ovine PL is capable of functional heterodimerization of GHR and PRLR and that when their cytosolic parts, coupled to the ECD of GM-CSF receptors, are heterodimerized by GM-CSF, they are capable of transducing biological signal.

International audience; When spermatogonia and primary spermatocytes (Go + Cl), uncontaminated by somatic testicular cells, were prepared from trout testes at various maturation stages and cultured alone, basal tritiated thymidine (H-3-Tdr) incorporation decreased throughout the reproductive cycle. It was unchanged by salmon gonadotropin (sGtH II), trout growth hormone (rhGH), testosterone, estradiol and 17 alpha,20 beta-dihydroprogesterone. Conversely, it was dose-dependently stimulated by rhIGF-I, with a mean ED(50) of 5.2 ng/ml and a mean maximum stimulation of 3.2-fold above control. When Go + Cl were cultured either in the presence of Sertoli cells or in Sertoli cell-conditioned medium (SCCM), basal H-3-Tdr incorporation was always decreased when the Sertoli cells were from spermatogenetic testes, but it was stimulated when they were from testes which were to resume spermatogenesis soon. Whatever the origin of the Sertoli cells, they always partly inhibited IGF-I stimulation. When present during either the co-cultures or the preparation of SCCM, sGtH II and rtGH had no effect when Sertoli cells were from spermatogenetic testes. In conclusion, IGF-I is a direct efficient stimulator of the proliferation of trout male germ cells, the effect of which is partly counteracted by Sertoli cells, sGtH II, rtGH and the 3 tested steroids are not directly active. While sGtH II has no Sertoli cell-mediated activity, further investigation is necessary to clarify whether the other tested molecules have such an activity.

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HEK-293T cells transiently transfected with ovine (o) GH receptor (GHR) and prolactin receptor (PRLR) constructs respectively tagged downstream with cyan or yellow fluorescent proteins were used to study ovine placental lactogen (oPL)-stimulated heterodimerization by fluorescence resonance energy transfer (FRET) microscopy. The oPL-stimulated transient heterodimerization of GHR and PRLR had a peak occurring 2.5–3 min after oPL application, whereas oGH or oPRL had no effect at all. The results indicate none or only little dimerization occurring before the hormonal stimulation. The effect of heterodimerization was studied by comparing activation of Janus kinase 2, signal transducer and activator of transcription (STAT)1, STAT3, STAT5, and MAPK in Chinese hamster ovary cells stably transfected with chimeric genes encoding receptors consisting of cytosolic and transmembrane parts of oGHR and oPRLR, extracellular domains of human granulocyte and macrophage colony-stimulating factor (hGM-CSF) receptor α or β, and cells transfected with the two forms (α or β) of PRLR and GHR. Functionality of those proteins was verified by hGM-CSF-induced phosphorylation of both intracellular PRLR and GHR domains and hGM-CSF-induced heterodimerization was documented by chimeric receptor coimmunoprecipitation. Homodimerization or heterodimerization of PRLRs and GHRs had no differential effect on activation of STAT5 and MAPK. However, heterodimerization resulted in a prolonged phosphorylation of STAT1 and in particular STAT3, suggesting that the heterodimerization of α-oGHR and β-oPRLR is able to transduce a signal, which is distinct from that occurring on homodimeric associations.

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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

International audience; Ce travail décrit la mise au point d'un dosage radio-immunologique (RIA) de l'hormone de croissance de la Daurade (sbGH). La sensibilité du dosage est de 0,4 ng/mL avec une ED50 de 1,74 ± 0,05 ng/mL. Les coefficients de variation intra- et inter-dosages sont respectivement de 3,4 et 8,8% à la dose de 1,7 ng/mL. Ni les hormones de croissance (GH) de mammifères, ni les gonadotrophines de la Carpe ou du Saumon chinook, ni la prolactine ovine, ni celle du Tilapia ne provoquent de réaction croisée. Les courbes de déplacement obtenues à partir de dilutions sériées de plasma et d'homogénats d'hypophyses de Sparidés (Daurade, Oblade, Sar commun, Pagre, Marbré) sont parallèles à la courbe standard (sbGH). Les homogénats hypophysaires des autres espèces de Perciformes (Serran chevrette, Mulet à grosse tête, Rouget de roche, Brochet de mer) produisent aussi des courbes de déplacement parallèles à la courbe standard. Par contre, les homogénats hypophysaires de la Sole, de la Rascasse rouge, de la Mostelle de roche, du Poisson rouge, de la Truite arc-en-ciel et de l'Anguille européenne, présentent peu ou ne présentent pas de réactivité croisée en fonction du dosage. Ces résultats semblent indiquer que les GH des Perciformes ont de nombreuses similarités de structure. Le dosage RIA de la GH de la Daurade peut donc être utilisé pour quantifier la GH des autres espèces de Sparidés, voire pour quantifier la GH des autres Perciformes si l'on prend soin de le valider pour chaque nouvelle espèce étudiée.

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National audience; Interaction between growth and reproduction occurs in many vertebrates and is particularly obvious at certain stages of the life cycle in fish. However the endocrine mechanisms involved in these phenomina have not been investigated to a great extent.

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International audience; The acute stress of handling followed by confinement for a period of 1 or 24 hr caused a typical stress response in rainbow trout (elevation of plasma ACTH and cortisol) and a significant reduction in the concentration of circulating growth hormone. The chronic stress of low oxygen levels in both crowded and uncrowded tanks of fish caused a significant elevation of circulating GH levels, an effect which was abolished by the provision of additional aeration to the rearing tanks. This chronic elevation of GH levels was closely correlated with an elevation of plasma cortisol in the same fish. These findings are discussed in relation to stress-induced growth suppression and to the links between the hypothalamic-pituitary-interrenal axis and somatotrope activity.

International audience; Ovine growth hormone (oGH) was administered to rainbow trout via an intraperitoneal cholesterol implant. After 21 days, plasma oGH levels were recorded as control group, less than 2 ng ml-1, i.e., not detectable, and oGH group, 19.2 +/- 2.8 ng ml-1. oGH-treated fish exhibited significantly increased whole-body growth rates, whole-body protein accretion rates, stimulated tissue protein synthesis, and tissue protein accretion rates. A dramatic decrease in white muscle protein concentration was also observed after oGH treatment. In some tissues (liver and stomach), elevated protein synthesis rates were the result of higher RNA/protein ratios. However, in other tissues (gill and ventricle), increased RNA activity accounted for the differences in rates of protein synthesis. The growth promoting effects of oGH on both whole-body and tissue protein turnover were generally accompanied with no change in the efficiency of deposition of newly synthesized protein. For the same ration size, the oGH group showed higher retentions of ingested nitrogen. It is concluded that oGH significantly enhances whole-body growth rates as a result of the stimulatory effect on protein synthesis rates with little effect on protein degradation.

International audience; Two experiments, one using 0 + the other 1 + rainbow trout, were conducted to investigate the effect of prolonged starvation on plasma growth hormone levels. The results from both experiments were essentially the same. As expected, starvation resulted in cessation of growth and in a lower coefficient of condition, whereas fed fish continued to grow and remained in good condition. Starvation had relatively little effect on the plasma cortisol level; in one experiment levels were elevated temporarily in starved fish, although by the end of the experiment there was no longer any difference between starved and fed fish, and in the other experiment plasma cortisol levels remained very low throughout the course of the experiment in both starved and fed fish. In contrast, in both experiments starvation had a pronounced effect on the plasma growth hormone level, which rose steadily during both experiments, such that it was six times higher after 1 month of starvation in 0 + fish, and five times higher after 6 weeks of starvation in 1 + fish. Thus, paradoxically, fed fish had very low plasma growth hormone levels and grew rapidly, whereas starved fish had elevated plasma growth hormone levels but did not grow. In both experiments a strong negative correlation was observed between the plasma growth hormone level and the coefficient of condition of the fish. The results are discussed with regard to the well-established metabolic changes that occur during starvation, and it is suggested that a major role of growth hormone during starvation is to aid in the mobilisation of fatty acids and glycerol from adipose stores.

International audience; Plasma growth hormone concentrations were determined in diploid and triploid rainbow trout of both sexes during sexual maturation. Diploid females grow large ovaries, whereas triploid female trout show no ovarian development. The plasma growth hormone concentration in triploid female trout remained low and unchanged throughout the study, whereas it rose slightly, but significantly, in the diploid females that matured, but not in those that remained immature. On the other hand, triploid males do develop tests like their diploid counterparts. In both groups spermiation was accompanied by a steady rise in the plasma growth hormone concentration. The results suggest that the elevated growth hormone concentration in mature male trout was a consequence not of reproduction per se, but of the loss of condition that accompanied spawning. This hypothesis was supported by the results from the females. Apart from a temporary loss in the mature diploids caused by stripping of the eggs, female trout did not lose condition, neither did they show any change in the plasma growth hormone concentration during the period when they ovulated. These results suggest that it was the nutritional insufficiency accompanying reproduction in male fish that caused the elevation in growth hormone concentration. In fact, a strong negative correlation between the plasma growth hormone concentration and the condition factor of the fish was observed.

National audience

Les récents développements de la génétique moléculaire offrent désormais la possibilité d’isoler virtuellement n’importe quel gène, de le muter in vitro, de modifier ses éléments régulateurs, de le réintroduire dans des cellules ou des organismes entiers (transgénèse) et donc, de moduler à volonté une fonction physiologique donnée. Ces possibilités ont été et sont encore appliquées à la fonction de croissance. Ainsi, les gènes du GRF (Growth Releasing Factor), de la GH (Growth Hormone) et de l’IGF1 (Insulin-like Growth Factor) ont été introduits dans des embryons de divers animaux. Ces transgènes se sont exprimés et ont conduit à une accélération de la croissance et à une augmentation de la taille des animaux accompagnée d’un assez profond changement de leur métabolisme. L’incapacité de moduler finement l’expression des transgènes chez les animaux transgéniques se traduit par une sécrétion exacerbée des hormones qui, elle-même, induit une série de désordres physiologiques rendant les animaux transgéniques peu performants. La transgénèse, si elle est devenue une routine chez la souris dans un certain nombre de laboratoires, reste difficilement réalisable à grande échelle chez la plupart des animaux domestiques. Des études approfondies sur les mécanismes de contrôle de l’expression des transgènes et sur les méthodes de transgénèse doivent donc être menées à bien pour que les manipulations génétiques deviennent une réalité dans les techniques d’élevage., Recent development in molecular biology makes the isolation of virtually any gene possible. The isolated gene can be mutated, in vitro, to modify its genetic message or its regulatory elements. It can then be reintroduced into cells or into the whole organism (transgenesis) and a physiological function can thus potentially be modified. These possibilities have been and still are being applied to animal growth. Genes coding for GRF (Growth Releasing Factor), GH (Growth Hormone), and IGF1 (Insulin-like Growth Factor) have been introduced into embryos of various animal species. These transgenes were expressed and this led to an acceleration of growth and to an increase in animal size. This phenomenon was accompanied by significant changes in the metabolism of the animals. The fact that the expression of the transgenes used could not be modulated led to an over secretion of GH, which is responsible for various physiological disorders, rendering most of the transgenic animals expressing a GH transgene of low interest for production. Although transgenesis has become a routine experiment in a certain number of laboratories, it remains relatively difficult on a large scale using most domestic animals. Further studies on the mechanisms which control transgene expression and on methods leading to transgenesis must be conducted before genetic engineering can really contribute to an improvement in animal breeding.

Highly purified tilapia (Sarotherodon mossambicus) prolactin and growth hormone added to culture medium of rabbit mammary gland explants specifically stimulated casein synthesis. The synthesized casein was quantified by an immunoprecipitation and further identified by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. In addition, the lactogenic activity of the fish hormones was determined by measuring the accumulation of β-casein mRNA using a 3H-labeled DNA complementary to the β-casein mRNA as a probe in a molecular hybridization. Moreover, tilapia prolactin was able to compete slightly with [125I]prolactin for the binding to rabbit mammary gland prolactin receptor. The lactogenic activities of the tilapia prolactin and growth hormone estimated by the rabbit casein assay were about 10 and 100 times lower, respectively, than the activity of ovine prolactin, which was used as a reference.

International audience; A method for the purification of chinook Salmon (Oncorhynchus tshawytscha) GH, which retains its biological activity, is described. The biological activity was investigated with an established radioreceptor assay using liver membranes from pregnant rabbits and bovine GH as standard and labelled hormone. The enrichment of the preparation was checked with electrophoresis (SDS-PAGE). Extraction and further steps were carried out using low molarity alkaline buffer (pH 8–10, M = 100 mM). Three chromatography steps were performed (Concanavalin-A sepharose, Bio-gel P60, DEAE). Ion exchange chromatography was performed under isocratic conditions (using a 50 cm column). Two isoforms (sGH1 and sGH2) were isolated. The purification yield is 0.7% compared to lyophilized pituitaries. The molecule is homogeneous in SDS-PAGE. Contamination by prolactin, gonadotrophin and corticotrophin is negligible (< 0.5%). It could be demonstrated that the biological activity of the preparation is maintained since this preparation stimulates the growth of juvenile trout (Salmo gairdneri) and binds specifically (35%) to trout liver membranes.

International audience; To test if growth hormone, well known for its strong effect on fish growth, could be incorporated into the diet, bovine growth hormone (bGH) was introduced into the lumen of the digestive tract of trout yearling (Salmo gairdneri). Radioimmunoassay (RIA) and radioreceptorassay (RRA) were used to assess plasma concentration of bGH. In our experimental conditions, the concentration of bGH peaks after 1 hour, in treated fish only, attesting to the intestinal hormone transfer (coefficient of absorption is about 0.2%). Immunocytochemistry is used to follow the hormone transfer process. Most bGH molecules absorbed by enterocytes of the distal segment are found in the vacuoles (phagolysosomes) of the apical hyaloplasm. A small part escapes the intracellular degradation and is found in the intercellular space and in the interstitial space of the lamina propria. At this level, the granule cells trapped the antigenic hormone, as did immune cells. The results of this study indicate that oral administration of GH can be potentially used in fish culture.

International audience

International audience; Gill (Na+ -K+)-ATPase activity of juvenile salmon, Salmo salar L., increased “classically” from February to the end of April in experiments in two different years, and its level before transfer to seawater was correlated directly with seawater performance (survival, plsma osmotic pressure and plasma chloride levels). A thyroxine (T4) surge occurred 2–3 weeks before the peak of gill enzyme levels. After the T4 peak the fish were clearly euryhaline, but T4 levels were not correlated with seawater adaptability. They remained able to adapt rapidly to seawater for at least 1 month after the surge. Two significant increases of tri-iodothyronine (T3) occurred while the fish were in freshwater: transfer to seawater either decreased T3 and T4 or had no effect. In freshwater, plasma growth hormone (GH) levels rose sharply concomitant with the T3 peak, 2 weeks before peak gill ATPase activity. After transfer to seawater GH increased significantly, remaining high for 7–10 days, and returning to base levels after 14 days. GH appeared to play a major role in smolting and seawater adaptation.

Cet article dresse le bilan des connaissances sur le mode d'action des quelques facteurs endocriniens qui contrôlent la croissance des téléostéens et sur les possibilités d'applications éventuelles et les problèmes qu'elles présentent.

International audience; Plasma levels of prolactin (PRL), growth hormone (GH), cortisol, thyroxine and triidothyronine were measured in normally-growing seawater (SW) and freshwater (FW) smolts and in animals which had stunted after premature transfer to SW. PRL levels were highest in FW animals and there was no difference between SW stunts and smolts. GH levels were 4-5-fold higher in stunts than in FW or SW smolts. Thyroid hormones andcortisol were significantly lower in stunts. Interrenal activity, assessed in vitro, was depressed in stunts. Transfer of stunts into FW for 3 weeks resulted in a normalization of plasma hormone levels. The results are discussed in relation to the possible causes of stunting and the involvement of the endocrine system in growth retardation.

The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by antidiabetic sulfonylureas. Diazoxide opens ATP-sensitive K+ channels in adenohypophysis cells as it does in pancreatic beta cells and also induces a hyperpolarization (approximately 30 mV) that is also suppressed by antidiabetic sulfonylureas. As in pancreatic beta cells, glucose and antidiabetic sulfonylureas depolarize the adenohypophysis cells and thereby indirectly increase Ca2+ influx through L-type Ca2+ channels. The K+ channel opener diazoxide has an opposite effect. Opening ATP-sensitive K+ channels inhibits growth hormone secretion and this inhibition is eliminated by antidiabetic sulfonylureas.