SAT-282 Hypothalamic Pituitary Adrenal Axis Hyperactivity in Db/db Mice

Background: Patients with diabetes present hypercortisolemia, which may exacerbate not only glycemic control but also diabetic complications and fatty liver (1). Blood steroid hormone levels including corticosterone and aldosterone are high in db/db mice (2), although the mechanism is still unclear. Objective: To reveal the mechanism underlying the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in obese and diabetic condition. Method: Total RNA from hypothalamus, pituitary, and adrenal glands in ten-week-old db/db and db/+ mice were extracted and analyzed with DNA microarray and real-time PCR. Experiments were approved by the Institutional Animal Care and Use Committee. Results: Hypothalamic Crh mRNA expression was not changed in db/db mice, although Avp expression was 2.8-fold higher than db/+ mice. Pituitary Crhr1 and Pomc expression were higher (3.0- and 7.0-fold, respectively), and Nr3c1 expression was lower (0.7-fold) in db/db mice than db/+ mice. Adrenal Mc2r, Nr5a1, Cyp11b1, and Cyp11b2 were higher in db/db mice than db/+ mice (1.7-, 1.7-, 2.2-, 1.3-fold, respectively). Conclusion: Increased expression of tropic hormone receptors and abrogated negative feedback system may be responsible for HPA axis hyperactivity in db/db mice. Reference: (1) Chiodini I et al. Diabetes Care. 2007 Jan;30:83–8. (2) Hofmann A et al. Horm Metab Res. 2017 Jan;49:43–49.