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UBC Theses and Dissertations

Organizational effects of gonadal hormones on the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor responses in male and female rats Innala, Leyla


Neonatal gonadal hormones during critical periods of development can irreversibly alter the adult hypothalamic-pituitary-adrenal (HPA) axis. The aims of this thesis were to investigate the role of neonatal gonadal hormones to 1. have direct organizational effects on the HPA axis or via indirect effects on corticosterone binding globulin that lead to compensatory changes in HPA output and 2. if changes in HPA output are met by changes in glucocorticoid receptor (GR) responses. To assesses these questions, the neonatal hormone milieu in Long Evan rats were manipulated in males by blocking the conversion of testosterone to estradiol with an aromatase blocker (ATD) and in females by administering testosterone propionate (TP). As adults, we assessed the influence of neonatal hormone manipulations on plasma corticosterone levels and GR activation in response to acute and repeated restraint exposure. GR responses were assessed using western blots to analyze GR translocation (nuclear/ nuclear and cytoplasm) and phosphorylation of GR at the serine 211 site (Ser211). We then assessed if changes in GR translocation and Ser211 followed restraint induced changes in total and estimated free CORT levels. Our results showed significant differences in corticosterone levels in neonatal ATD treated male and TP treated female rats compared to their same sex control groups under basal-naïve conditions and after restraint exposure, respectively. In both sexes, for GR translocation and Ser211, there was a main effect of restraint stress exposure, and overall significant positive correlations with CORT (total and estimated free) levels. GR translocation was lower in neonatal TP treated females, with no effect in Ser211. Differences between male neonatal ATD and Sham groups were observed compared to untouched controls in Ser211, indicating the effects of the neonatal ATD treatment appear to be due to effects of surgery and gonadal hormone milieu exposure. Adult gonadal hormone levels differed between female neonatal groups, which are likely due to organizational effects of the neonatal treatments. The current study demonstrates neonatal gonadal hormones have long lasting effects on adult corticosterone outputs and sequential GR responses.

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