Thesis (Ph. D.)--University of Kentucky, 2003. / Title from document title page. Document formatted into pages; contains xix, 74p. : ill. Includes abstract. Includes bibliographical references (p. 62-72).

Thesis (M.S.)--University of Wyoming, 2007. / Title from PDF title page (viewed on July 25, 2008). Includes bibliographical references (p. 68-84).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1981. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 158-178).

Thesis (M.S.)--University of Wisconsin--Madison, 1981. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 66-70).

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Although the effect of inhaled corticosteroids (ICS) on the hypothalamic- pituitary-adrenal axis (HPA) has been regarded as a “benign physiological response”, a survey published in 2002 suggested that adrenal crisis is more common in asthmatic children on ICS than previously thought. Relying on clinical features to detect chronic adrenal insufficiency secondary to corticosteroids may not be wise, as these are non-specific and can therefore easily be missed. Accurate biochemical assessment of the whole axis to detect subclinical HPA suppression (HPAS) is thus desirable. A review of the literature indicates that basal adrenal function tests, including plasma cortisol profiles, do not identify which children can appropriately respond to stress. There is no evidence to suggest that the degree of the physiological adjustment of the HPA to ICS and/or nasal steroids (by reducing basal cortisol production), predicts HPAS. Cortisol profiles should therefore only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Only two tests, considered as gold standard adrenal function tests [the insulin tolerance test (ITT) and the metyrapone test] can assess the integrity of the whole axis. / AFRIKAANSE OPSOMMING: Die outeurs van ´n opname wat in 2002 gepubliseer is stel voor dat ´n bynierkrisis meer algemeen by asmatiese kinders, wat inhalasie kortikosteroïede ontvang, voorkom as wat voorheen gedink is. Dit is strydig met die gevestigde opvatting dat die effek van IKS op die hipotalamiese-hipofise-bynier-as (HHB) ’n “goedaardige fisiologiese reaksie” is. Die kliniese kenmerke van kroniese bynierontoereikendheid sekondêr tot die gebruik van kortikosteroïede (KS) is nie-spesifiek en gevolglik onbetroubaar. ´n Akkurate biochemiese toets van subkliniese HBB onderdrukking (HHBO) sou gevolglik waardevol wees. ´n Literatuur oorsig toon dat toetse van basale bynierfunksie, insluitend plasma kortisol (K) profiele, nie kinders uitken wat toepaslik op stres sal reageer nie. Daar is geen bewyse dat die graad van fisiologiese aanpassing van die HHB, soos aangedui deur laer K-vlakke, na die gebruik van IKS en/of nasale steroïede (NS), HHBO voorspel nie. Serum K profiele is dus slegs van waarde om die sistemiese aktiwiteit van verskillende IKS en toedieningsstelsels te ondersoek. Slegs twee toetse, naamlik die insulien toleransie toets (ITT) en die metyrapone -(MTP)-toets (wat beide as die goue standaard van bynier funksie beskou word), kan die integriteit van die hele as meet.

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

Neuropeptide hormones arose early in evolution. Multigene families in vertebrates are proposed to have arisen initially in early vertebrates by genome duplication events. In its simplest form, the theory suggests that the copy of a duplicated, ancestral single gene diverged in sequence, and possibly function, from its original match. My goal was to understand the structural and functional evolution of two neuropeptides, gonadotropinreleasing hormone (GnRH), a member of a single gene family, and pituitary adenylate cyclase-activating polypeptide (PACAP), a member of a multigene superfamily of hormones. GnRH is the primary regulator of reproduction in vertebrates, but the evolutionary origin of GnRH is not clear. In the protochordate tunicate Ciona intestinalis, I found there are two genes that encode GnRH peptides, however each gene encodes different GnRH peptides. Furthermore, these peptides are novel structures for GnRH and quickly induce spawning in Ciona, suggesting a novel and direct action for GnRH in the control of reproduction. In studies of the novel form of GnRH in lake whitefish, wfGnRH, I provide proof wfGnRH is a gonadotropin-releasing form in whitefish by showing it to be an activator of pituitary gonadotropin and growth hormone gene expression, and is colocalized in the forebrain region. PACAP is a hormone structurally related to glucagon and has been tightly conserved in structure during evolution. PACAP is produced as either a 27 or a 38 amino acid form in vertebrates, whereas in one tunicate studied to date, PACAP is produced from each of two genes as a 27 amino acid form. PACAP regulates several endocrine systems and has direct and indirect actions on metabolism, growth, and reproduction, and is well-known for its ability to potently secrete insulin in laboratory testing. I studied a number of species to increase our understanding of PACAP gene diversity in evolution. I was unable to identify a PACAP-like gene in the tunicate species, C. intestinalis. However, I identified a number of novel PACAP peptide structures in nine fish species by molecular biological and bioinformatic approaches. I was able to identify a second copy of a PACAP gene in five of the nine species. Using these data, I constructed a phylogenetic relationship for prohormones for PACAP in chordates and propose a updated explanation for the evolution of the PACAPfglucagon superfamily of genes in vertebrates. Using morpholino-based knockdown of the PACAP peptides in zebrafish early development, I showed that each copy of these two genes is functional and important in normal development in zebrafish, suggesting that divergence in function of the two different PACAP genes coincided with divergence in sequence. I also studied mice to determine the proposed role for PACAP in themogulation. Recently, the pups born to a new model of mouse with a targeted disruption of the PACAP gene (PACAP-null) have been found to have disruption of normal lipid and carbohydrate metabolism and die early in the second postnatal week. Furthermore it has been determined this phenotype is temperature sensitive. I hypothesized that there is a disruption of the thyroid axis in these mice that contributes to their problems with thermogenesis, and because these mice have a compromised adrenergic response, they are more sensitive to obesity. I showed that there is twice as much of the active form of thyroid hormone (TH), 3,5,3'-triiodothyronine (T3), in PACAP-null mice compared to their wildtype littermates. Mice reared at different temperatures (21, 24 and 28 °C) had increased survival with increasing temperature from 14% surviving at 21°C to 79 % at 28°C, and mice held at 28°C had lower levels of THs compared to 21°C. Treatment of PACAP-null mice with methimizole decreased their level of T3 and increases their survival suggesting the levels of T3 in mice at 21°C are toxic. Mice raised at 28°C on one of two diets, regular chow (low fat) and high fat were studied for difference in appetite and in tolerance to obesity. There were no differences in either appetite or many obesity-related parameters such as mass, fed and fasted glucose levels, fat distribution or plasma levels of leptin in PACAP-null mice compared to their sex- and diet-matched wildtype comparison groups. However, there was an increase in insulin sensitivity in PACAP-null mice fed a high fat diet.

Chan Chi-bun. / "May 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 162-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 82-89).