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Inhibition of hypothalamic aromatase activity by 5 Beta-dihydrotestosterone
M Schumacher1, R E Hutchison, J B Hutchison
1MRC Neuroendocrine Development and Behaviour Group, Institute of Animal Physiology, Babraham, Cambridge CB24AT, UK.
Journal of Neuroendocrinology
|February 14, 2009
Summary
In avian species, 5beta-dihydrotestosterone (5beta-DHT) inhibits aromatase, an enzyme crucial for producing 17beta-oestradiol. This suggests 5beta-reduction protects the developing brain from androgen effects during sexual differentiation.
Area of Science:
- Neuroendocrinology
- Steroid Metabolism
- Avian Biology
Background:
- Testosterone is converted to inactive 5beta-reduced metabolites (5beta-DHT and 5beta,3alpha-diol), particularly in young birds.
- The role of these metabolites in steroid inactivation and their potential direct effects on steroidogenic pathways are not fully understood.
Purpose of the Study:
- To investigate if 5beta-reduced testosterone metabolites directly inhibit enzymes producing biologically active steroids.
- To determine if 5beta-DHT or 5beta,3alpha-diol affect hypothalamic aromatase activity.
Main Methods:
- Hypothalamic homogenates from adult male doves were used to assay enzyme activity.
- 5beta-DHT and 5beta,3alpha-diol were added to these homogenates to assess their effects on aromatase.
Main Results:
- 5beta-DHT, but not 5beta,3alpha-diol, significantly inhibited hypothalamic aromatase activity in adult male doves.
- This inhibition by 5beta-DHT was also observed in hypothalamic homogenates from newly hatched birds, correlating with high 5beta-reduced metabolite production.
Conclusions:
- 5beta-reduced metabolites of testosterone can directly inhibit key enzymatic pathways for active steroid production.
- High 5beta-reductase activity during avian sexual differentiation may protect the brain from androgenic influences by suppressing oestrogen synthesis via aromatase inhibition.
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