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Title: Mechanism(s) underlying the attenuated ACTH responses to stress in pregnancy
Author: Ma, S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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The aim of this project was to investigate the possible mechanism(s) underlying the attenuated hypothalamic-pituitary-adrenal (HPA) axis response to stressors during pregnancy at the level of the anterior pituitary. We found that the reduced HPA axis activity during pregnancy was not due to changes in the sensitivity of corticotrophs in the anterior pituitary, but to the decreased secretion particularly of vasopressin and possibly corticotropin-releasing hormone (CRH) from the hypothalamus. The reduced CRH and vasopressin secretion during pregnancy is a result of action of neurosteroid metabolites of progesterone as a 5α-reductase inhibitor reversed the attenuated adrenocorticotrophic hormone (ACTH) secretory response to stress. By in situ hybridisation, we found a progressive decrease in proopiomelanocortin (POMC) mRNA expression in the anterior pituitary during pregnancy. However, there was no change in ACTH content. Compared with expression in the anterior pituitary of virgin rats, in late pregnancy (day 21), CRH receptor subtype 1 (CRHR1) mRNA expression was not changed, vasopressin receptor subtype lb (VlbR) mRNA expression was reduced, and glucocorticoid receptor (GR) mRNA was increased. We also measured large conductance potassium channel (BK) and the splice variant of the BK channel, STREX, mRNA expression and found no change during pregnancy. Corticotropin-releasing hormone binding protein (CRHBP) mRNA expression was elevated by 30 min restraint stress in the anterior pituitary, but there were no differences between virgin and pregnant rats. The reduced stress-induced ACTH response during pregnancy is predominantly the consequence of reduced vasopressin release, with secondary changes in corticotrophs. The central changes may be due to the inhibitory action of allopregnanolone on CRH and vasopressin secretion from the hypothalamus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available