RESEARCH - Inflammation and sex hormone metabolism

[Guest guest]

BASIC AND CLINICAL ASPECTS OF NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC

DISEASES

Volume 1069 published June 2006

Ann. N.Y. Acad. Sci. 1069: 236-246 (2006). doi: 10.1196/annals.1351.021

Copyright © 2006 by the New York Academy of Sciences

Inflammation and Sex Hormone Metabolism

MARTIN SCHMIDTa, HEIDRUN NAUMANNa, CLAUDIA WEIDLERb, MARTINA SCHELLENBERGa,

SVEN ANDERSc AND RAINER H. STRAUBb

a Institute of Biochemistry II, Hospital of the

Friedrich-Schiller-University, 07740 Jena, Germany b Department of Internal

Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany c

Department of Orthopedic Surgery, University Regensburg, Bavarian Red Cross

Hospital, 93077 Bad Abbach, Germany

The incidence of autoimmune diseases is higher

in females than in males. In both sexes, adrenal hormones, that is,

glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are

inadequately low in patients when compared to healthy controls. Hormonally

active androgens are anti-inflammatory, whereas estrogens are

pro-inflammatory. Therefore, the mechanisms responsible for the alterations

of steroid profiles in inflammation are of major interest. The local

metabolism of androgens and estrogens may determine whether a given steroid

profile found in a subject's blood results in suppression or promotion of

inflammation. The steroid metabolism in mixed synovial cells, fibroblasts,

macrophages, and monocytes was assessed. Major focus was on cells from

patients with rheumatoid arthritis (RA), while cells from patients with

osteoarthritis served as controls. Enzymes directly or indirectly involved

in local sex steroid metabolism in RA are: DHEA-sulfatase, 3-hydroxysteroid

dehydrogenase, 17-hydroxysteroid dehydrogenase, and aromatase (CYP19), which

are required for the synthesis of sex steroids from precursors, 5-reductase

and 16-hydroxylase, which can be involved either in the generation of more

active steroids or in the pathways leading to depletion of active hormones,

and 3-reductase and 7-hydroxylase (CYP7B), which unidirectionally are

involved in the depletion of active hormones. Androgens inhibit

aromatization in synovial cells when their concentration is sufficiently

high. As large amounts of estrogens are formed in synovial tissue, there may

be a relative lack of androgens. Production of 5-reduced androgens should

increase the local anti-inflammatory activity; however, it also opens a

pathway for the inactivation of androgens. The data discussed here suggest

that therapy of RA patients may benefit from the use of nonaromatizable

androgens and/or the use of aromatase inhibitors.

http://www.annalsnyas.org/cgi/content/abstract/1069/1/236

Not an MD