Inadequate Glucocorticoid Secretion in Experimental Arthritis in Rats Is Closely Linked to Impaired Mitochondria and Reduced Lipid Breakdown in the Adrenal Cortex

Christine Wolff¹, Katharina Krinner¹, Josef Schröder² and Rainer H. Straub³, ¹Laboratory of Exp. Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital, Regensburg, Germany, ²Department of Phatology, University Hospital, Regensburg, Germany, ³Department of Internal Medicine I, Laboratory of Exp. Rheumatology and Neuroendocrino-Immunology, University Hospital of Regensburg, Regensburg, Germany

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Animal models, glucocorticoids and mitochondria

Session Information

Title: Rheumatoid Arthritis - Animal Models I

Session Type: Abstract Submissions (ACR)

Background/Purpose: In rheumatoid arthritis a functional deterioration of the HPA-axis in form of inadequately low secretion of glucocorticoids in relation to severity of inflammation can be detected. The reasons for this phenomenon are not known. The purpose of this study was to find possible reasons responsible for adrenal insufficiency during arthritis.

Methods: DA rats were immunized with type II collagen in incomplete Freund adjuvant to induce arthritis. Plasma corticosterone was evaluated by RIA and plasma ACTH by ELISA. Adrenal cholesterol was quantitatively studied by Sudan-III staining and scavenger receptor class BI (SR-BI, the HDL receptor) by immunohistochemistry. Fluorescent NBD-cholesterol uptake kinetics were analysed by flow cytometry. Ultrastructural morphology of adrenocortical mitochondria and lipid droplets was studied by electron microscopy.

Results:

Initially increased corticosterone and ACTH levels were reduced to baseline levels in the later phase of the disease. Serum levels of corticosterone relative to IL-1β were markedly lower in arthritic than control animals (inadequacy). Cholesterol storage in adrenocortical cells and expression of SR-BI did not differ between immunized and control rats. However, number of impaired mitochondria largely increased during the course of arthritis (maximum on day 55), and this was paralleled by reduced numbers of activated cholesterol droplets (inhomogenous droplets relevant for generation of glucocorticoids). In addition, number of normal mitochondria positively correlated with serum corticosterone levels.

Conclusion: This first study on adrenal reasons for inadequate glucocorticoid secretion in arthritis demonstrated impaired mitochondria and altered cholesterol breakdown paralleled by low corticosterone levels in relation to ongoing inflammation.

Disclosure:

C. Wolff,
None;

K. Krinner,
None;

J. Schröder,
None;

R. H. Straub,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/inadequate-glucocorticoid-secretion-in-experimental-arthritis-in-rats-is-closely-linked-to-impaired-mitochondria-and-reduced-lipid-breakdown-in-the-adrenal-cortex/