RESEARCH - Inflammation and sex hormone metabolism

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Ann N Y Acad Sci. 2006 Jun;1069:236-46.

Inflammation and sex hormone metabolism.

Institute of Biochemistry II, Hospital of the Friedrich-Schiller-University,

07740 Jena, Germany. Schmidt@...

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, 3beta-hydroxysteroid dehydrogenase,

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

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

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

more active steroids or in the pathways leading to depletion of active

hormones, and 3alpha-reductase and 7alpha-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

5alpha-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.

PMID: 16855150

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16855150

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