This project investigated postnatal development of the adrenocortical function in captive American kestrels (Falco sparverius) employing measurements of basal and stress-induced levels of corticosterone at specific developmental stages. Chicks aged 10-days exhibited partially functioning adrenocortical systems with baseline levels comparable to adults. The ability to respond to external stressors increased through postnatal development and by the age of 22 days, stress-induced maximal levels of corticosterone were indistinguishable from those of one-year old adults, and levels of 28-day old birds were significantly higher than these adults. In addition, baseline and maximum stress-induced levels of corticosterone at all ages were significantly higher in first-hatched chicks than all other siblings and these effects grew stronger through development. These results suggest that the brain-pituitary-adrenal axis in this semi-altricial species is (1) already partially developed in young chicks and (2) only becomes fully functional when behavioral and neuromuscular development is nearly complete. Furthermore, results from this study suggest that hatching asynchrony has an effect on this variation in stress-induced maximal levels of corticosterone during the latter half of postnatal development, with a higher degree of hatching asynchrony leading to larger disparity in adrenocortical function between first- and fourth-hatched chicks. This adrenocortical disparity resulting from female-mediated hatching asynchrony may potentially lead to both brood-reduction and brood survival under diametric food conditions, ensuring that the female's reproductive fitness is maximized in varying habitats. Variation of adrenocortical function among siblings may increase female efficiency in raising a brood of fit chicks, maximizing her reproductive success.

Arginine vasopressin (AVP) is a hypothalamic nonapeptide which regulates the hypothalamic-pituitary-adrenal axis response to stress by stimulating the secretion of adrenocorticotropin (ACTH) from corticotroph cells of the anterior pituitary. This effect is mediated by binding of AVP to the pituitary vasopressin receptor (V1bR). The V1bR belongs to the G protein-coupled receptor (GPCR) super family. Repeated stimulation of anterior pituitary cells with AVP has been shown to produce a loss of responsiveness to subsequent AVP stimulation. This phenomenon appears to be mediated by desensitisation of the V1bR, and may be due to phosphorylation of the receptor by G protein-coupled receptor kinase 5 (GRK5). The aim of this research was to establish and validate methods that would allow the role of GRK5 in the desensitisation of V1bR to AVP stimulation to be investigated. As no isoform specific inhibitors for GRK5 were available, HEK293 cells transiently transfected with the rat V1bR were used as a model system for this research. This allowed RNA interference (RNAi) to be used to knockdown GRK5 expression. The protocol for RNAi-mediated knockdown of GRK5 was established as part of this research. Protocols for Western blotting and qRT-PCR were also established to allow the RNAi-mediated knockdown of GRK5 protein and mRNA to be measured. Transfection of HEK293 cells with 10nM GRK5-targeting small interfering RNAs (siRNAs) reduced the expression of GRK5 protein to 53.4% ± 3.4% (mean ± SEM) of that seen in untreated control cells at 84 hours after transfection, while GRK5 mRNA levels were reduced to 28.7% ± 1.9% (mean ± SEM) of that of control cells 48 hours after transfection. An experimental protocol was designed in this research that would coordinate the RNAi-mediated knockdown of GRK5 with transient transfection of the HEK293 cells with the rV1bR. Since, activated V1bRs couple to Gq/11 and stimulate the production of inositol phosphates (IPs), the responsiveness of the V1bR can be determined by measuring the accumulation of [H³]-IPs in cells labelled with [H³]-myo-inositol. In the protocol designed, the effect of GRK5 knockdown on V1bR desensitisation is determined by stimulating HEK293 cells expressing the rV1bR (and previously transfected with GRK5-targeting siRNA) with 0nM or 100nM AVP for 0, 5, 15, 30 or 60 minutes, and comparing the accumulation if IPs over time with that of cells that are not transfected with GRK5-targeting siRNA. This protocol can be used in future to investigate the role of GRK5 in V1bR desensitisation, and may be adapted to determine if other GRK isoforms are involved in V1bR desensitisation.

Includes bibliographical references (leaves 228-257). / xxii, 257 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to determine the impact of maternal undernutrition during late gestation and during the periconceptional and gestational periods on fetal growth, fetal blood pressure and the fetal hypothalamo-pituitary adrenal axis in the sheep. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2001

Maintenance of normal health requires an intact stress system capable of mounting the metabolic, autonomic, behavioural and motor responses required for coping with or avoiding physiological and pathological challenges. The neuroendocrine component of this response principally involves the hypothalamic-pituitary-adrenal (HPA) and sympatho-adrenomedullary (SAM) axes. Impaired regulation of these axes has been implicated in the pathogenesis and expression of numerous disease states, however, it has proved very difficult to reproducibly activate the HPA and SAM axes and no single test exists that can reliably and safely be used to study these systems in man. Carbon dioxide (CO2) is the principal regulator of respiration, acid-base balance and behavioural-state arousal in humans. Paradigms of CO2 inhalation have been used in psychiatric research to investigate panic and anxiety disorders, but evaluation of other components of the stress response to CO2 has not previously been performed. I hypothesised that a single breath of 35% CO2 would be a simple and reliable tool for the evaluation of the stress response in humans. A single breath of four doses of CO2 (5%, 25%, 35% and 50%) was administered to 9 healthy volunteers in a randomised, single blind fashion. Subjective symptoms of anxiety increased in a dose-dependent manner. Inhalation of a single breath of 35% CO2 stimulated significant ACTH (p = 0.006), noradrenaline (p < 0.0001), cortisol (p = 0.02) and prolactin (p = 0.002) release. It also provoked an acute pressor response and an associated bradycardia (p < 0.0001 for both). No significant habituation of psychological, HPA or cardiovascular responses was seen when this dose was repeated after one week (n = 10) or 6 months (n = 5). It was apparent that a single breath of 35% CO2 reliably and safely produced SAM and HPA axis activation and further studies were then undertaken to assess the mechanism by which the observed responses occurred and its potential clinical implications. Administration of naltrexone (an opiate antagonist) to 10 normal volunteers disinhibited the HPA axis (p < 0.0004), whilst administration of metyrapone (a cortisol synthesis inhibitor) significantly reduced baseline cortisol (p < 0.03) levels. However, this alteration in HPA axis activity had no effect on either cardiovascular or psychological responses. Further, in a study of 8 breastfeeding mothers (a state associated with physiological suppression of the HPA axis) suckling significantly reduced plasma cortisol levels compared with control (p = 0.002) and bottle-feeders (p = 0.003). Despite this cortisol, systolic blood pressure (SBP), heart rate and psychological responses to 35% CO2 were not affected

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 114-134).

Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, 2008. / "March 2008" Bibliography: leaves xxvi-xliii. Also available in print form.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 45-56). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 45-56). Also available on the Internet.

Thesis (M.Sc.) - Carleton University, 2007. / Includes bibliographical references (p. 66-91). Also available in electronic format on the Internet.

Thesis (PH. D.)--Michigan State University. Dept. of Psychology, 2008. / Title from PDF t.p. (viewed on Sept. 8, 2009) Includes bibliographical references (p. 157-178). Also issued in print.