Testosterone
is Locally Metabolized in Human Brain Tumors, with Possible
Qualitative and Quantitative Changes in its Effects by
H. J. Stuerenburg, Breivik, M. J. A. Puchner, F Lohmann,
and K. Kunze
Received:
October 24, 1997
Accepted: November 14, 1997
Abstract
We
investigated the metabolism of testosterone by human brain tumors.
Activation and deactivation of steroid hormones by enzymatic
transformation in the target tissue or organ is an important
regulating mechanism which modifies the effects of steroid hormones.
Steroid hormones can act in human brain and in brain tumors
via estrogen. androgen, glucocorticoid and progestin receptors.
The 5-alpha-reductase activity [metabolism of testosterone to
dihydrotestosterone], the 3-alpha-hydroxysteroid oxidoreductase
activity [metabolism of 5-alpha-dihydrotestosterone to 5-alpha-androstane-3-alpha.17b-diol],
the aromatase activity [metabolism of testosterone to estradiol-17b],
the 17b-hydroxysteroid oxidoreductase
activity [metabolism of testosterone to 4-androstene-3.17-dione]
and the production of 4-androstane-3.17-dione were studied in
37 brain tumors.
We
detected a mean 5-alpha-reductase activity of 4 52 (±
1 91) x 10-17 Mol/mg protein/min (±
standard error), a 3-alpha-hydroxysteroid oxidoreductase activity
of 1.76 (±0.58) x 10 -17 Mol/mg
protein/min, an aromatase activity of 3.86 (a: 0.67) x 10-18
Mol/mg protein/min, a 17b-hydroxysteroid
oxidoreductase activity of 5 77 (± 1.87) x 10-17
Mol/mg protein/min and a mean synthesis of androstanedione of
1 03 (± 0 23) x 10 -18 Mol/mg protein/min.
Our findings demonstrate the local transformation of testosterone
in human brain tumors, and consequently the activation (5-alpha-reductase).
deactivation (3-alpha-hydroxysteroid oxidoreductase) and induction
of estrogenic activity (aromatase) The local enzymatic transformation
of testosterone in human brain tumors described here could lead
both to an activation and a deactivation of the testosterone
effect. This local metabolism could be important for the local
effect of testosterone. In previous reports, considerable importance
has been placed on the measurement of steroid hormone receptor
concentrations in brain tumors, however, in the interpretation
of these data the local metabolism of steroids demonstrated
here must be taken into account, or erroneous conclusions will
inevitably be drawn.
