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We studied whether long-term use of mesterolone (12 weeks and longer) changed the pattern of steroid metabolites in urine from male subjects. We noticed an increase in dehydroepiandrosterone (DHEA) levels from 211-4 +/- 130.5 ug/die to 9943.8 +/- 6564.7 ug/die in the urine of all subjects tested. This increase was significant. After mesterolone administration was discontinued, DHEA levels decreased to their initial value. DHEA levels showed the smallest increase in those subjects having high plasma FSH levels. Perhaps the delta 4 pathway of testosterone synthesis may be preferred in these three subjects. We suppose that mesterolone has a blocking effect on the delta 5 pathway of testosterone synthesis. DHEA from the DHEA-pool can be used for testosterone synthesis and mesterolone seems to block some enzymes in the synthetic pathway. We were not able to detect a decrease in plasma testosterone levels during mesterolone use because of technical problems. Moreover, our patients told us that they felt ill after discontinuing mesterolone use; it may be possible that there is a psychotropic DHEA-effect during mesterolone use.

The aim of the study was to determine a biochemical basis for the augmented oxidative metabolism found in mononuclear leukocytes (MNL) of patients with active psoriasis. Dehydroepiandrosterone (DHEA) is known to inhibit glucose-6-phosphate dehydrogenase (G-6-PDH). We determined the activity of G-6-PDH as well as the penetration and metabolism of DHEA - diminished plasma concentrations of which have been found in psoriatics previously - in 16 patients with active psoriasis and 16 controls. MNL in patients with psoriasis possessed 52% more (p less than 0.05) G-6-PDH activity, based on cell number, and 34% more (p less than 0.05) activity, based on soluble protein. No difference in DHEA penetration and metabolism in MNL was found between psoriatics and controls, in contrast with previous findings of reduced penetration and increased reduction in erythrocytes of psoriatics. We conclude that the enhanced G-6-PDH activity in MNL of patients with active psoriasis is not due to altered DHEA penetration or metabolism.

In the plasma of psoriatics and controls the steroids dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol were determined by radioimmunoassay. Corresponding earlier findings obtained by photometric methods in psoriatics the plasma level of dehydroepiandrosterone is increased and that of androstenediol is decreased.

A radioimmunological method is described for the determination of dehydroepiandrosterone and 5-androsten-3 beta, 17 beta-diol in plasma. Interfering cross-reactions of the antiserum of 5-androsten-3 beta, 17 beta-diol with testosterone and pregnenolone make it necessary to separate the steroids by thin-layer chromatography before their final determination. With respect to sensitivity, this method is superior to the commonly used photometric and gas-chromatographic analytical procedures. For both steroids the limits of detection are about 170 fmol.

In patients with psoriasis in extra- and intracellular deficiency of dehydroepiandrosterone can be demonstrated which leads to an activation of the pentose-phosphate cycle. This dehydroepiandrosterone deficiency is caused by an increased intracellular activity of 17 beta-hydroxysteroid-dehydrogenase. This results in an increased formation of the reduction product androstendiol, which is unable to inhibit the glucose-6-phosphate dehydrogenase, the keye enzyme of the pentose-phosphate cycle. In addition, a decreased penetration of the steroid through the membrane of erythrocytes is demonstrable, by which the intracellular deficiency of dehydroepiandrosterone is still augmented. The effects of this dehydroepiandrosterone deficiency are changes in the humoral regulation of events in growth and proliferation in patients with psoriasis.

When total DHEA, G-6-PDH activity, and c-AMP were determined in human neoplastic mammary tissue and corresponding normal tissue the G-6-PDH activity in the former tissue greatly exceeded that found in normal tissue. On the other hand, a remarkable decrease of total DHEA and c-AMP could be detected in cancer tissue, hinting at the participation of DHEA in the intracellular regulation of G-6-PDH and c-AMP levels.

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