The clinical practice of administering a precursor molecule, known as a prohormone, into the body with the specific intention of allowing endogenous enzymatic pathways in peripheral tissues to convert it into a more potent, biologically active hormone. This strategy, exemplified by the introduction of dehydroepiandrosterone (DHEA) to increase local androgen and estrogen levels, leverages the body’s natural intracrinology to achieve targeted hormonal optimization. It offers a more nuanced approach than direct hormone replacement by allowing local tissue regulation to govern the final active hormone concentration.
Origin
The concept is rooted in the principles of endocrinology and pharmacology, where the metabolism of administered compounds is utilized to achieve a therapeutic effect. The term became highly relevant with the clinical application of DHEA, a weak steroid that serves as a substrate for potent sex hormones. This approach acknowledges the differential expression of converting enzymes across tissues, making the introduction a key method for personalized hormonal support.
Mechanism
The mechanism relies entirely on the presence and activity of specific steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase and aromatase, in the target tissues. The introduced prohormone, such as DHEA, enters the circulation and is then taken up by cells, where these enzymes catalyze its conversion into active androgens (like testosterone) or estrogens (like estradiol) based on local tissue needs. This metabolic conversion pathway ensures that the final hormonal action is regulated at the cellular level, minimizing systemic overexposure to potent hormones.
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