Androgen synthesis pathways delineate the specific, multi-step enzymatic routes within the adrenal glands and gonads responsible for the de novo creation of androgenic hormones, such as testosterone and dihydrotestosterone (DHT). These pathways are fundamentally important for both male and female physiology, regulating muscle mass, bone health, libido, and energy levels. Proper function relies on the sequential action of several cytochrome P450 enzymes and hydroxysteroid dehydrogenases.
Origin
The concept originates from the field of steroid biochemistry, established through classic experiments that mapped the conversion of cholesterol into various steroid hormones, beginning in the mid-20th century. The term ‘androgen’ derives from the Greek words andros (man) and -genes (producing), referring to their role in masculinization, although they are crucial for all sexes. Mapping these complex enzymatic steps was critical for understanding congenital adrenal hyperplasia and other endocrine disorders.
Mechanism
The primary mechanism starts with cholesterol being converted to pregnenolone in the mitochondria, which is the foundational steroidogenic precursor. Pregnenolone is then shuttled through either the delta-5 or delta-4 pathway, undergoing sequential modifications, including hydroxylation and dehydrogenation, catalyzed by specific enzymes like 17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase. These conversions ultimately yield DHEA, androstenedione, and finally, the potent androgens testosterone and DHT, which then exert their effects via nuclear receptor binding.
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