Learning Objectives

• Understand how LH stimulates Leydig cells.
• Describe the Gs → cAMP → StAR pathway in testosterone synthesis.
• Explain how testosterone provides negative feedback.
• Recognize the role of aromatization to estradiol in males.

LH Receptor Activation

Leydig cells express receptors for Luteinizing Hormone (LH). LH is a peptide hormone that binds to a Gs protein–coupled receptor.

Gs → Adenylyl Cyclase → ↑ cAMP → ↑ Protein Kinase A (PKA)

This signaling cascade activates the Steroidogenic Acute Regulatory Protein (StAR), the rate-limiting step in steroid synthesis. StAR transports cholesterol into the mitochondria, initiating testosterone production.

Testosterone Distribution

• Diffuses into Sertoli cells → Maintains high intratesticular testosterone for spermatogenesis.
• Enters systemic circulation → Produces secondary sexual characteristics.

Exam Pearl: Intratesticular testosterone levels are much higher than serum levels and are essential for sperm production.

Activity

Negative Feedback Regulation

Circulating testosterone provides negative feedback at:

• The Hypothalamus → ↓ GnRH
• The Anterior Pituitary → ↓ LH

Activity

Aromatization to Estradiol

Leydig cells convert a portion of testosterone into estradiol via the enzyme aromatase. Estradiol contributes to:

• Bone maturation
• Epiphyseal closure
• Additional negative feedback regulation

Activity