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Patrice Mollard - One of the best experts on this subject based on the ideXlab platform.

  • The Processes of Anterior Pituitary Hormone Pulse Generation
    Endocrinology, 2018
    Co-Authors: Paul Le Tissier, Tatiana Fiordelisio Coll, Patrice Mollard
    Abstract:

    More than 60 years ago, Geoffrey Harris described his "neurohumoral theory," in which the regulation of Pituitary Hormone secretion was a "simple" hierarchal relationship, with the hypothalamus as the controller. In models based on this theory, the electrical activity of hypothalamic neurons determines the release of hypophysiotropic Hormones into the portal circulation, and the Pituitary simply responds with secretion of a pulse of Hormone into the bloodstream. The development of methodologies allowing the monitoring of the activities of members of the hypothalamic-vascular-Pituitary unit is increasingly allowing dissection of the mechanisms generating hypothalamic and Pituitary pulses. These have revealed that whereas hypothalamic input is required, its role as a driver of pulsatile Pituitary Hormone secretion varies between Pituitary axes. The organization of Pituitary cells has a key role in the modification of their response to hypophysiotropic factors that can lead to a memory of previous demand and enhanced function. Feedback can lead to oscillatory Hormone output that is independent of pulses of hypophysiotropic factors and instead, results from the temporal relationship between Pituitary output and target organ response. Thus, the mechanisms underlying the generation of pulses cannot be generalized, and the circularity of feedforward and feedback interactions must be considered to understand both normal physiological function and pathology. We describe some examples of the clinical implications of recognizing the importance of the Pituitary and target organs in pulse generation and suggest avenues for future research in both the short and long term.

  • Multiple-scale neuroendocrine signals connect brain and Pituitary Hormone rhythms
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Nicola Romanò, Anne Duvoid-guillou, David Hodson, Agnès O Martin, Patrice Mollard
    Abstract:

    Significance The hypothalamo–Pituitary axis controls a wide range of homeostatic processes, including growth, stress, and reproduction. Despite this fact, the hypothalamic neuron firing patterns that lead to slowly evolving Pituitary Hormone rhythms remain enigmatic. Here, we used in vivo amperometric recordings in freely behaving mice to investigate how tuberoinfundibular neurons release dopamine (DA) at the median eminence (ME) to control Pituitary prolactin secretion. Using this approach, we show that DA release occurs as multiple locally generated and time-scaled secretory events, which are integrated over a range of minutes across the ME. These results provide a broad physiological mechanism for the dialogue that occurs between the brain and Pituitary to dictate Hormone rhythms over multiple timescales, from ultradian to seasonal.

  • Multiple-scale neuroendocrine signals connect brain and Pituitary Hormone rhythms.
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Nicola Romanò, Agnès O Martin, Anne Guillou, David J. Hodson, Patrice Mollard
    Abstract:

    Small assemblies of hypothalamic "parvocellular" neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting Pituitary Hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of Pituitary prolactin secretion, a key reproductive Hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz-10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local-global integration to connect brain-Pituitary rhythms and pace Hormone secretion.

George Vlotides - One of the best experts on this subject based on the ideXlab platform.

Christoph J. Auernhammer - One of the best experts on this subject based on the ideXlab platform.

Nicola Romanò - One of the best experts on this subject based on the ideXlab platform.

  • Multiple-scale neuroendocrine signals connect brain and Pituitary Hormone rhythms
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Nicola Romanò, Anne Duvoid-guillou, David Hodson, Agnès O Martin, Patrice Mollard
    Abstract:

    Significance The hypothalamo–Pituitary axis controls a wide range of homeostatic processes, including growth, stress, and reproduction. Despite this fact, the hypothalamic neuron firing patterns that lead to slowly evolving Pituitary Hormone rhythms remain enigmatic. Here, we used in vivo amperometric recordings in freely behaving mice to investigate how tuberoinfundibular neurons release dopamine (DA) at the median eminence (ME) to control Pituitary prolactin secretion. Using this approach, we show that DA release occurs as multiple locally generated and time-scaled secretory events, which are integrated over a range of minutes across the ME. These results provide a broad physiological mechanism for the dialogue that occurs between the brain and Pituitary to dictate Hormone rhythms over multiple timescales, from ultradian to seasonal.

  • Multiple-scale neuroendocrine signals connect brain and Pituitary Hormone rhythms.
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Nicola Romanò, Agnès O Martin, Anne Guillou, David J. Hodson, Patrice Mollard
    Abstract:

    Small assemblies of hypothalamic "parvocellular" neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting Pituitary Hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of Pituitary prolactin secretion, a key reproductive Hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz-10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local-global integration to connect brain-Pituitary rhythms and pace Hormone secretion.

Anne Barlier - One of the best experts on this subject based on the ideXlab platform.

  • Genetic analysis of adult Slovenian patients with combined Pituitary Hormone deficiency
    Endocrine, 2019
    Co-Authors: Katica Bajuk Studen, Alexandru Saveanu, Thierry Brue, Anne Barlier, Magdalena Avbelj Stefanija, Marija Pfeifer
    Abstract:

    Purpose Among genetic causes of combined Pituitary Hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in Pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. Methods Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes ( PROP1/HESX1/LHX4/LHX3/POU1F1 ) involved in the Pituitary development following an established algorithm. Results In seven out of 23 patients (30%) a specific mutation in genes encoding Pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. Conclusions Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of Pituitary transcription factor genes are extremely rare.

  • MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined Pituitary Hormone deficiency
    European Journal of Endocrinology, 2016
    Co-Authors: Frederic Castinetti, Rachel Reynaud, Alexandru Saveanu, Alain Enjalbert, Anne Barlier, M.-h. Quentien, Nicolas Jullien, Claire Rochette, Thierry Brue
    Abstract:

    Over the last 5 years, new actors involved in the pathogenesis of combined Pituitary Hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge.

  • Combined Pituitary Hormone deficiency: current and future status
    Journal of Endocrinological Investigation, 2015
    Co-Authors: Frederic Castinetti, Rachel Reynaud, Alexandru Saveanu, Anne Barlier, M.-h. Quentien, N. Jullien, E. Marquant, C. Rochette, J.-p. Herman, Alain Enjalbert
    Abstract:

    Over the last two decades, the understanding of the mechanisms involved in Pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-Pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype–genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple Pituitary deficiencies, the etiology of most (80–90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed Pituitary deficiencies, differential diagnosis of a Pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined Pituitary Hormone deficiencies, associated or not with extra-Pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

  • Genetic causes of combined Pituitary Hormone deficiencies in humans.
    Annales d'Endocrinologie, 2012
    Co-Authors: Frederic Castinetti, Rachel Reynaud, Alexandru Saveanu, Anne Barlier, Thierry Brue
    Abstract:

    Congenital hypopituitarism is a rare disease, usually induced by mutations of genes coding for transcription factors involved in Pituitary development. PROP1 mutations represent the first cause of identified congenital hypopituitarism. Current techniques only identify 10-20% of congenital hypopituitarism etiologies, suggesting that new techniques are needed to improve this ratio. This should lead to a better management and follow-up of patients presenting with combined Pituitary Hormone deficiencies.

  • congenital Pituitary Hormone deficiencies role of lhx3 lhx4 genes
    Expert Review of Endocrinology & Metabolism, 2008
    Co-Authors: Frederic Castinetti, Rachel Reynaud, Alexandru Saveanu, Alain Enjalbert, Anne Barlier, M.-h. Quentien, Frédérique Albarel, Thierry Brue
    Abstract:

    LHX3 and LHX4 are LIM domain transcription factors involved in the early steps of Pituitary organogenesis. They are necessary for the proper differentiation of Rathke's pouch that gives rise to the anterior Pituitary lobe. Mutations of these transcription factors are involved in congenital hypopituitarism: to date, nine mutations of LHX3 have been reported, responsible for variable Pituitary Hormone deficiencies and extraPituitary manifestations, including limited neck rotation. By contrast, only five LHX4 mutations have been reported, responsible for variable Hormone deficiencies, and Pituitary/intracranial abnormalities. Future investigations will aim to better understand human Pituitary organogenesis and to shed light on the interspecies differences in the roles of these transcription factors.