Schmidt, M. and Kreutz, M. and Loeffler, Georg and Schoelmerich, Juergen and Straub, Rainer H. (2000) Conversion of dehydroepiandrosterone to downstream steroid hormones in macrophages. JOURNAL OF ENDOCRINOLOGY, 164 (2). pp. 161-169. ISSN 0022-0795, 1479-6805
Full text not available from this repository. (Request a copy)Abstract
Dehydroepiandrosterone (DHEA) is a ubiquitous adrenal hormone with immunomodulatory effects such as inhibition of the production of monokines. Whether DHEA itself or the downstream steroids are the immunomodulatory effector hormones in target cells is not known. In this study, we investigated the conversion of DHEA to downstream steroid hormones in target macrophages. Within 1 day of culture with radiolabeled DHEA, monocyte-derived macrophages converted DHEA to significant amounts of Delta 5-derivatives such as 160H-DHEA, 3 beta,17 beta-androstenediol (A'diol), and 3 beta,16 alpha,17 beta-androstenetriol (A'triol). However, the production of Delta 4-steroids (androstenedione (A'dione), testosterone (T), and 16OH-T) and estrogens (estrone, estradiol, and estriol) was relatively low. Further cultivation of macrophages for 5 days with radiolabeled DHEA resulted in a significant (P<0.05) increase of the molar amounts of A'triol (P=0.012), 16OH-T (P=0.008), and estriol (P=0.003). In contrast to monocyte-derived macrophages, monocytes did not express aromatase mRNA, which was demonstrated by RT-PCR (P<0.01). Furthermore, DHEA in macrophages significantly inhibited one of the downstream converting enzymes, the aromatase, which was not demonstrated in the presence of the typical macrophage activator, lipopolysaccharide (LPS) (P<0.01). In conclusion, conversion of DHEA to physiologically relevant amounts of Delta 5- and Delta 4-steroids and estrogens was demonstrated in monocyte-derived macrophages. The conversion depends on maturation of monocytes and local factors such as the presence of LPS. The conversion of DHEA leads to an increase of downstream effector hormones in target macrophages which may be an important factor for local immunomodulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; POSTMENOPAUSAL WOMEN; ENDOCRINE REGULATION; AROMATASE INDUCTION; MONONUCLEAR-CELLS; GENE-EXPRESSION; DHEA-SULFATE; FACTOR-ALPHA; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2022 11:53 |
| Last Modified: | 07 Jun 2022 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42857 |
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