Development of the Hypothalamus-Pituitary-Adrenal Regulatory Loop Using Mice Deficient in Steroidogenic Gene Cyp11a1

• Main Authors: Menq-Rong Wu, 吳孟容
• Other Authors: Bon-Chu Chung
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/83103702835356256756

碩士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 98 === The hypothalamus -pituitary-adrenal axis (HPA axis) is important for stress response. CORT can inhibit the activation of the HPA axis. During mouse development, there is a stress hypo-responsive period (SHRP) at postnatal days 2 to12 when the body does not respond to stress well. It is suspected that CORT level is so low during SHRP that it could not inhibit the HPA axis. However, the development of the HPA axis during this period has not been carefully examined. We studied SHRP using a mouse line deficient in Cyp11a1 (Cyp11a1WT-neo/WT-neo), which encodes an enzyme that catalyzes the first step of steroidogenesis important for the secretion of steroids. Cyp11a1WT-neo/WT-neo mice expressed decreased level of CYP11A1 in adrenal and brain. Their plasma corticosterone (CORT) level was lower and adrenocorticotropic hormone level was higher. The CRH and POMC transcript levels were higher, and CRHR1 mRNA level was lower in Cyp11a1WT-neo/WT-neo mice. These data indicate the HPA axis is inhibited by CORT. Besides, pregnenolone and corticosterone levels in the brain were lower. Furthermore, Cyp11a1WT-neo/WT-neo adrenal was disorganized and smaller compared with the wildtype adrenal. Our results suggest that: (1) Feedback inhibition of the HPA axis was present during SHRP (2) Loss of steroids lead to the disruption of adrenal zonation.