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The intracrine sex steroid biosynthesis pathways
1Oncology, Molecular Endocrinology and Human Genomics Research Center (CREMOGH), Department of Molecular Medicine, Laval University and Laval University Hospital Research Center (CRCHUL), Quebec, Canada. Van.Luu-The@crchul.ulaval.ca <Van.Luu-The@crchul.ulaval.ca>
Progress in Brain Research
|May 19, 2010
Summary
New research reveals that adrenal dehydroepiandrosterone (DHEA) is converted into active sex steroids like estradiol (E2) and dihydrotestosterone (DHT) in peripheral tissues. These intracrine pathways are crucial for hormone production in both men and post-menopausal women.
Area of Science:
- Endocrinology
- Molecular Biology
- Biochemistry
Background:
- Traditional gonadal steroidogenesis pathways differ from recent molecular findings.
- New technologies like gene cloning and mass spectrometry reveal novel steroid biosynthesis routes.
Purpose of the Study:
- To present steroidogenesis in light of new findings on estradiol (E2) and dihydrotestosterone (DHT) biosynthesis.
- To highlight intracrine pathways in peripheral tissues using adrenal dehydroepiandrosterone (DHEA).
Main Methods:
- Utilized molecular cloning, pangenomic expression studies, and real-time PCR for mRNA quantification.
- Employed stably transfected steroidogenic enzymes, enzymatic activity analysis, and mass spectrometry.
- Analyzed tissue-specific enzyme actions and molecular evolution of steroidogenic enzymes.
Main Results:
- Demonstrated biosynthesis of E2 and DHT from adrenal DHEA in peripheral intracrine tissues.
- Identified pathways that bypass testosterone as an intermediate, unlike gonadal routes.
- Showcased the critical role of these pathways in post-menopausal women and for a significant portion of androgens in men.
Conclusions:
- Intracrine pathways utilizing adrenal DHEA are vital for sex steroid production in both sexes.
- Tissue-specific enzymes facilitate DHEA conversion, particularly important in post-menopausal women.
- Molecular evolution explains interspecies differences in steroid metabolism.
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