This project was designed to investigate the ability of newborn infants to respond to surgical stress and to consider alternative methods of anaesthetic management in view of their hormonal and metabolic response. Concentrations of blood metabolites (glucose, lactate, pyruvate, alanine, acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids, triglycerides) and plasma hormones (insulin, glucagon, noradrenaline, adrenaline, aldosterone, corticosterone, cortisol, 11-deoxycorticosterone, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, cortisone) were measured in blood samples drawn before and after surgery, at 6, 12 and 24 hours postoperatively. Urinary total nitrogen and 3-methylhistidine/ creatinine ratios were measured for 3 days postoperatively. Peri-operative management was standardised and severity of surgical stress was assessed by a scoring method. In a preliminary study of 29 neonates, substantial hormonal and metabolic changes demonstrated the ability of neonates to mount a stress response to surgery. Compared to adult responses, the magnitude of these changes was greater but their duration was remarkably short-lived. Significant differences were found between preterm and term neonates, and between neonates given different anaesthetic management. Randomised controlled trials were designed for studying the effects of : (1) halothane anaesthesia in 36 neonates undergoing general surgical procedures, (2) fentanyl anaesthesia in 16 preterm neonates undergoing ligation of patent ductus arteriosus, (3) high-dose fentanyl anaesthesia in 13 neonates undergoing cardiac surgery. On comparing the responses of neonates within each trial, the stress response of neonates given halothane or fentanyl anaesthesia was diminished; their : (a) catecholamine responses were decreased or abolished, (b) glucocorticoid responses were suppressed, (c) changes in blood glucose and gluconeogenic precursors were decreased, (d) postoperative analgesic requirements were reduced, and (e) their clinical condition after surgery was more stable. The neonatal response was related to the severity of surgical stress, as assessed by the scoring method. Thus, hormonal and metabolic changes following surgery in preterm and term neonates are distinctly different from those of adult patients; the lack of adequate anaesthesia may cause an accentuation of the stress response.

The hypothalamus is a central regulator of energy homeostasis. Recently, proglucagon-derived peptides have emerged as potential appetite regulators. The proglucagon gene is expressed in the periphery and also in selective hypothalamic neurons. The regulation of hypothalamic proglucagon by two key regulators of energy balance, insulin and leptin, remains unstudied. Central glucagon-like peptide (GLP)-1 receptor (GLP-1R) activation by exendin-4, a long-acting GLP-1R agonist, induces anorexia; however, the specific hypothalamic neuronal populations activated by exendin-4 remain largely unknown. The role of GLP-2 as a central appetite regulator is poorly understood. In this thesis, using murine hypothalamic cell lines and mice as experimental models, mechanisms involved in the direct regulation of proglucagon gene by insulin and leptin were studied, and the actions of exendin-4 and GLP-2 on hypothalamic neuropeptides were determined. It was found that insulin and leptin regulate hypothalamic proglucagon mRNA by activating Akt and signal transducer and activator of transcription 3, respectively. Insulin and leptin did not regulate human proglucagon promoter regions, but affected proglucagon mRNA stability. In mice, intracerebroventricular exendin-4 and GLP-2 induced anorexia, activated proopiomelanocortin- and neuropeptide Y-expressing neurons in the arcuate nucleus and neurotensin- and ghrelin-expressing neurons in major hypothalamic appetite-regulating regions. In the hypothalamic neuronal models, exendin-4 and GLP-2 activated cAMP-response element-binding protein/activating transcription factor-1, and regulated neurotensin and ghrelin mRNA levels via a protein kinase A-dependent mechanism. Overall, the in vivo and in vitro findings suggest that these neuropeptides may serve as potential downstream mediators of exendin-4 and GLP-2 action. This research demonstrates direct regulation of hypothalamic proglucagon by insulin and leptin in vitro, and reports a previously unrecognized link between central GLP-1R and GLP-2R activation and regulation of hypothalamic neuropeptides. A better understanding of the regulation of hypothalamic proglucagon and central GLP-1R and GLP-2R activation is important to further expand our knowledge of feeding circuits.

The hypothalamus is a central regulator of energy homeostasis. Recently, proglucagon-derived peptides have emerged as potential appetite regulators. The proglucagon gene is expressed in the periphery and also in selective hypothalamic neurons. The regulation of hypothalamic proglucagon by two key regulators of energy balance, insulin and leptin, remains unstudied. Central glucagon-like peptide (GLP)-1 receptor (GLP-1R) activation by exendin-4, a long-acting GLP-1R agonist, induces anorexia; however, the specific hypothalamic neuronal populations activated by exendin-4 remain largely unknown. The role of GLP-2 as a central appetite regulator is poorly understood. In this thesis, using murine hypothalamic cell lines and mice as experimental models, mechanisms involved in the direct regulation of proglucagon gene by insulin and leptin were studied, and the actions of exendin-4 and GLP-2 on hypothalamic neuropeptides were determined. It was found that insulin and leptin regulate hypothalamic proglucagon mRNA by activating Akt and signal transducer and activator of transcription 3, respectively. Insulin and leptin did not regulate human proglucagon promoter regions, but affected proglucagon mRNA stability. In mice, intracerebroventricular exendin-4 and GLP-2 induced anorexia, activated proopiomelanocortin- and neuropeptide Y-expressing neurons in the arcuate nucleus and neurotensin- and ghrelin-expressing neurons in major hypothalamic appetite-regulating regions. In the hypothalamic neuronal models, exendin-4 and GLP-2 activated cAMP-response element-binding protein/activating transcription factor-1, and regulated neurotensin and ghrelin mRNA levels via a protein kinase A-dependent mechanism. Overall, the in vivo and in vitro findings suggest that these neuropeptides may serve as potential downstream mediators of exendin-4 and GLP-2 action. This research demonstrates direct regulation of hypothalamic proglucagon by insulin and leptin in vitro, and reports a previously unrecognized link between central GLP-1R and GLP-2R activation and regulation of hypothalamic neuropeptides. A better understanding of the regulation of hypothalamic proglucagon and central GLP-1R and GLP-2R activation is important to further expand our knowledge of feeding circuits.

Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references (leaves 70-81). / vii, 86 leaves, bound ill. (some col.) 29 cm

Xenoestrogens are chemical pollutants that can disrupt the endocrine system of animals by binding to and activating the estrogen receptor(s). They include both natural and synthetic steroid estrogens, together with a variety of estrogen mimicking chemicals such as 4-nonylphenol, bisphenol A and various pesticides. In vertebrates, estrogens play a fundamental role in reproduction, in somatic cell function, the regulation of calcium and water homeostasis. Exposure to xenoestrogens may therefore have unscheduled effects on these systems that can potentially compromise species survival. With the ever-increasing number of xenoestrogens identified and detected in the environment, together with the fact that they are seldom detected alone, there is a need to develop specific and sensitive biomarkers to detect estrogenic activity of chemicals in the environment when present alone and in mixtures. In this study, the effect of selected xenoestrogens was assessed using an in-vitro yeast estrogen screen (YES) both individually and in mixtures and in-vivo in a native fish species, the Murray rainbowfish (Melanotaenia fluviatilis).

Thesis (Ph. D.)--University of Washington, 1995. / Vita. Includes bibliographical references (leaves [118]-142).

"Publication authorized September 2, 1943." / Includes bibliographical references (p. 69-75).

Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Endocrinology and Animal Biosciences." Includes bibliographical references.

Thesis (M.S.)--Duquesne University, 2004. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 106-115 ) and index.

Thesis (M.S.)--University of Wisconsin--Madison, 1983. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 81-94).