Neuroendocrine regulation of hypothalamo-pituitary function in the fetus

• Main Author: Hagan, Donna Marie
• Published: University of Edinburgh 1996
• Subjects: 611
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651928

During fetal development there is a progressive maturation of the hypothalamo-pituitary-adrenal (HPA) axis which is responsible for co-ordinated fetal maturation and the onset of birth. The aim of this thesis is to investigate the neuroendocrine regulation of the developing HPA axis. The first approach was to investigate the role of putative neurotrophic factors in the functional maturation of hypothalamic arginine vasopressin (AVP) neurons. The role of AVP in the release of adrenocorticotropic hormone (ACTH) has been extensively demonstrated but little is known about the factors controlling the development of AVP neurons. The objective of this study was to chart the growth and development of AVP neurons in cell culture in response to various neurotrophic factors. Functional maturation of the neurons was assessed in terms of the secretory response to potassium-induced depolarisation whilst development of neuronal morphology was to be monitored by immunocytochemistry. Fetal rat hypothalamic neurons were cultured in the presence and absence of insulin-like growth factor-1 (IGF-1), which has been implicated as a putative neurotrophic factor, for periods of up to 20 days. IGF-1 had no significant effect on either basal or stimulated levels of AVP secretion, suggesting that AVP neurons do not appear to be the specific target population for IGF-1 within the developing fetal hypothalamus. Despite extensive screening of several different antibodies, we were unable to specifically identify AVP neurons in culture by immunocytochemistry. These results demonstrate the existence of an endogenous inhibitory system regulating the release of ACTH, α-MSH and prolactin from the fetal pituitary gland. However, these results do not support the hypothesis that peptides released upon removal of the inhibitory dopaminergic tone are capable of eliciting the secretion of cortisol from the fetal adrenal gland.