In mammals, the pituitary-derived neuropeptide adrenocorticotropic hormone (ACTH) is a major regulator of adrenocortical steroidogenesis and hormone secretion. However, the mechanism by which adrenal growth is governed by pituitary signals and the role of the pituitary in early adrenal development remain to be investigated. In this work the model organism zebrafish was used to elucidate pituitary adrenal interactions during early vertebrate development. The adrenal homologue in zebrafish is located in the head kidney and termed interrenal organ. The work deals with the analysis of pituitary-interrenal interactions by using pituitary mutants, gene-knockdown embryos and pharmacological interventions. As prerequisite to the main study, zebrafish pomc gene was cloned and characterized and the interrenal organogenesis in wild-type zebrafish was analysed. / Adrenocorticotropin (ACTH) entsteht aus Proopiomelanocortin (POMC) in den corticotrophen Zellen der Hypophyse und ist ein zentraler Regulator der adrenalen Steroidogenese. Allerdings wirkt ACTH in vitro antiproliferativ und differenzierend und es ist daher unklar, wie adrenales Wachstum durch die Hypophyse gesteuert wird. Insbesondere liegen widerspüchliche Befunde zum Einfluss der Hypophyse auf die Entwicklung der Nebenniere vor. In dieser Arbeit wurde der Zebrafisch als Modellorganismus eingesetzt, um die Interaktionen zwischen Hypophyse und Nebennieren während der frühen Entwicklung weiter aufzuklären. Das Homolog der Nebenniere beim Zebrafisch wird als Interrenalorgan bezeichnet und ist in die Kopfniere eingebettet. In der vorliegenden Dissertation sollte die Wechselwirkung zwischen Hypophyse und Interrenalorgan während der Organogenese des Interrenalorgans durch die Untersuchung verschiedener hypophysärer Mutanten, Gen-knockdown Embryonen und durch pharmakologische Intervention untersucht werden. Die Klonierung und Charakterisierung des pomc-Gens und die Analyse der normalen Entwicklung des Interrenalorgans beim Zebrafisch schaffen dabei die Voraussetzungen für die Hauptstudie.

国立情報学研究所で電子化したコンテンツを使用している。

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Tierärztl. Hochsch., Diss., 2003--Hannover.

Tierärztl. Hochsch., Diss., 2003--Hannover.

No description available.

Abstract EXAMINATION OF BASAL NEUROENDOCRINE LEVELS IN OIF/OEF/OND VETERANS By Sage E. Hawn, B.S. A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2015. Major Director: Ananda B. Amstadter, PhD. Associate Professor Departments of Psychiatry, Psychology, & Human and Molecular Genetics High rates of combat exposure exist among veterans of the recent conflicts, and are associated with debilitating mental health conditions, including posttraumatic stress disorder (PTSD). Numerous psychosocial and biologic factors are associated with PTSD, including the HPA-axis. The present study aimed to compare baseline neuroendocrine levels by trauma group (PTSD, trauma exposed [TE], and non-trauma controls [NTC]) among a sample of young veterans. An exploratory aim was to examine potential moderators of the relation between PTSD and basal cortisol/ACTH. Group differences in cortisol were nominally significant, with the NTC group having significantly higher cortisol than the PTSD group. Sleep disturbance was the only moderator of this relationship in cortisol, although lifetime trauma load significantly predicted basal cortisol across all models. No significant effects were demonstrated for ACTH. Examining effects of trauma on basal physiology provides a critical stepping ground for future investigations that may inform targeted prevention and intervention efforts.

Pituitary adenomas constitute about 15% of intracranial tumors, and about one-third of secretory pituitary adenomas produce ACTH. Corticotroph adenomas, a subset of pituitary adenomas staining positive for ACTH, are further categorized into functional (FCA) and silent (SCA) adenomas. FCAs result in central Cushing’s disease (CD) due to the resulting excess of cortisol secretion stimulated by ACTH secretion through hormone disruption while SCAs exhibit mass effects and show increased aggression as compared to its functional counterpart. Obesity and cardiovascular disease, resulting from hypercortisolism in functional adenomas, increase patient morbidity while the invasive nature of silent adenomas increases mortality. Trans sphenoidal surgery (TSS) is the best available treatment option for cotricotroph adenomas, but tumor recurrence is common. We sought to identify differential genetic drivers of sporadic FCAs and SCAs in order to better characterize these tumors and develop novel treatment options. We examined 17 adenomas including 12 FCA and 5 SCA as well as 2 corticotroph hyperplasia (CH) tissue samples. We performed next generation sequencing using OncoPanel versions 2 and 3 on patients operated on at Brigham and Woman’s Hospital between 2008 and 2018 and determined to have a corticotroph adenoma. 3 of 4 FCA patients screened for USP8 mutations contained variants previously described in CD including USP8S718P and USP8S719del. 3 of the 12 FCA patients screened for mutations in ARID1B contained novel variants and 1 patient contained a variant previously described in large intestine adenocarcinomas. Additionally, SNPs were commonly identified in genes responsible for epigenetic regulation implicating histone modification as a therapeutic target. We identified recurrent copy number variants (CNV) in both FCAs and SCAs. Gains of 6p, 20q and 21q were frequently observed in FCAs alongside less common losses in 11p and 19q. Significant amplifications of chromosome 12 were detected in SCAs with single nucleotide deletions in chromosome 10. Furthermore, we report diverging genomic disruption between subtypes associated with functional hormone status. Our data identifies novel genetic drivers in subclasses of corticotroph adenomas and indicate distinct genomic profiles associated with hormone secretion and clinical presentation. Further research is required to better elucidate the role of these genetic variants and how they influence tumorigenesis and hormone production.

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Bibliography: leaves 161-189. / xx, 189 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of the series of experiments described in this thesis was to investigate the functional characteristics of the subpopulations of the corticotrophs in the fetal pituitary during normal development and after chronic intrauterine stress. / Thesis (Ph.D.)--University of Adelaide, School of Molecular and Biomedical Sciences, Discipline of Physiology, 2004