How is testosterone synthesized?

Testosterone is a vital hormone that plays a crucial role in the development and maintenance of male physical and physiological characteristics. Testosterone is primarily synthesized in the Leydig cells of the testes under the regulation of the hypothalamic-pituitary-gonadal (HPG) axis.
The synthesis of testosterone begins with the transport of cholesterol into the inner mitochondrial membrane of Leydig cells. This is the rate-limiting step in testosterone production and is facilitated by a protein complex called transducein. Inside the mitochondria, cholesterol undergoes a series of chemical reactions catalyzed by specific enzymes to produce testosterone.

• The first step involves the conversion of cholesterol to pregnenolone by an enzyme called CYP11A1.


• Pregnenolone then undergoes two successive reactions involving the enzymes 3β-HSD and CYP17A1 to form androstenedione.


• Androstenedione leaves the mitochondria and in the smooth endoplasmic reticulum is converted to testosterone by the enzyme 17β-HSD.

Therefore, the full pathway for testosterone biosynthesis is:

Cholesterol → Pregnenolone → Progesterone → 17α-hydroxyprogesterone → Androstenedione → Testosterone

The rate of testosterone synthesis is regulated by the hypothalamic-pituitary gonadal (HPG) axis. Here's a quick overview of how this works:

• The hypothalamus secretes gonadotropin releasing hormone (GnRH) which stimulates the pituitary gland.


• The pituitary gland then releases two gonadotropins:
  
  
  
  
  • luteinizing hormone (LH)
  
  
  • and follicle stimulating hormone (FSH)
  
  


• LH then binds to Leydig cells in the testes and upregulates expression of enzymes and proteins involved in testosterone synthesis, notably:
  
  
  
  
  • Steroidogenic acute regulatory protein (StAR) - transports cholesterol
  
  
  • CYP11A1 and 17β-HSD - catalyzes reactions
  
  
  • Transducein - transports cholesterol
  
  


• The increasing testosterone levels exert a negative feedback on GnRH and LH secretion to maintain homeostasis.

If you suspect you may have low testosterone levels or related symptoms, have your testosterone levels checked by a medical professional. The physicians at Harmony Hormone Center specialize in the diagnosis and treatment of hormone disorders including testosterone deficiency. Harmony Hormone Center uses state-of-the-art testing and offers science-based hormone therapies including testosterone replacement therapy for men with low testosterone. Contact them today to book an appointment with one of their highly-qualified physicians.

In summary, the key steps in testosterone biosynthesis are:

1. Transport of cholesterol into mitochondria
   
   
   
   
   • Rate-limiting, facilitated by transducein
   
   


2. Conversion of cholesterol into pregnenolone
   
   
   
   
   • Catalyzed by CYP11A1
   
   


3. Formation of androstenedione from pregnenolone
   
   
   
   
   • Involves 3β-HSD and CYP17A1
   
   


4. Conversion of androstenedione to testosterone
   
   
   
   
   • Catalyzed by 17β-HSD
   
   

The HPG axis regulates this process by modulating expression of steroidogenic proteins and enzymes. Diagnosis and management of abnormalities in testosterone levels should be performed by hormone therapy experts like those at Harmony Hormone Center.