Cystic fibrosis in mice elicits multiple changes in pituitary gland function

Chronic illness frequently involves metabolic and physiologic changes that are not directly related to the primary insult. Because these changes, such as growth retardation, pubertal delay, and cachexia, are generally undesirable, research has been devoted to elucidating their causes. Many of these changes are likely related to altered hormone levels, including those that are components of pituitary pathways. Cystic fibrosis (CF) is a multi-organ chronic disease that elicits growth retardation and pubertal delay in both humans and mice. Based on these observations, we hypothesized that CF mice would have altered endocrine system behavior. This dissertation details changes in endocrine pathways involving the pituitary gland in CF mice, and discusses the physiological relevance of these changes.; One endocrine pathway altered in CF mice involved growth regulation. CF mice were substantially smaller in weight and height than their WT counterparts. Analysis of growth regulatory hormones revealed that levels of serum Insulin-like growth factor-1 (Igf-1) were significantly reduced in CF mice. Serum Igf-1 levels also significantly correlated to weight and height of mice, consistent with its role as a regulator of growth. Since these findings were consistent with models of malnutrition causing growth retardation, we assessed food intake, and found that CF mice consumed a similar amount of food as WT mice. These results suggest that CF mice experience malabsorption, leading to an energy deficit and a downregulation of growth.; Another altered pituitary pathway in CF mice involved proopiomelanocortin (Pomc), a peptide that is a precursor to many hormones. CF mice had substantially elevated levels of both pituitary Pomc mRNA and one of its derivatives, plasma alpha-melanocyte stimulating hormone (alpha-Msh). This was the first report of an animal model of chronic disease displaying elevated levels of alpha-Msh, levels of which are also altered in some human diseases. Elevated levels of alpha-Msh may affect many processes that could influence CF disease severity.; This dissertation presents several changes in the function of the endocrine system in CF mice. We anticipate that further study of CF mice will help elucidate the causes and sequelae of these changes in human CF and chronic illness in general.