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Role of 11β-HSD type 1 in abnormal HPA axis activity during immune-mediated arthritis.

Role of 11β-HSD type 1 in abnormal HPA axis activity during immune-mediated arthritis.
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Sattler J, Tu J, Stoner S, Li J, Buttgereit F, Seibel M, Zhou H, Cooper MS,


Sattler J, Tu J, Stoner S, Li J, Buttgereit F, Seibel M, Zhou H, Cooper MS, (click to view)

Sattler J, Tu J, Stoner S, Li J, Buttgereit F, Seibel M, Zhou H, Cooper MS,

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Endocrine connections 2018 01 31() pii EC-17-0361
Abstract

Patients with chronic immune-mediated arthritis exhibit abnormal hypothalamo-pituitary-adrenal (HPA) axis activity. The basis for this abnormality is not known. Immune-mediated arthritis is associated with increased extra-adrenal synthesis of active glucocorticoids by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. 11β-HSD1 is expressed in the central nervous system, including regions involved in HPA axis regulation. We examined whether altered 11β-HSD1 expression within these regions contributes to HPA axis dysregulation during arthritis. The expression of 11β-HSD1, and other components of glucocorticoid signalling, were examined in various brain regions and the pituitary gland of mice with experimentally-induced arthritis. Two arthritis protocols were employed: The K/BxN spontaneous arthritis model for chronic arthritis and the K/BxN serum transfer arthritis model for acute arthritis. 11β-HSD1 was expressed in the hippocampus, hypothalamus, cortex, cerebellum and pituitary gland. Hypothalamic 11β-HSD1 expression did not change in response to arthritis in either model. Pituitary 11β-HSD1 expression was however significantly increased in both chronic and acute arthritis models. Hippocampal 11β-HSD1 was decreased in acute but not chronic arthritis. Chronic, but not acute, arthritis was associated with a reduction in hypothalamic corticotropin-releasing hormone and arginine vasopressin expression. In both models, serum adrenocorticotropic hormone and corticosterone levels were no different from non-inflammatory controls. These findings demonstrate inflammation-dependent regulation of 11β-HSD1 expression in the pituitary gland and hippocampus. The upregulation of 11β-HSD1 expression in the pituitary during both chronic and acute arthritis, and thus an increase in glucocorticoid negative feedback, could contribute to the abnormalities in HPA axis activity seen in immune-mediated arthritis.

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