Testicular Function and Androgen Physiology

The testis has two coordinated jobs: making sperm and making androgens. Leydig cells in the interstitium synthesise testosterone under the control of luteinizing hormone, while Sertoli cells within the seminiferous tubules support spermatogenesis under the combined influence of follicle-stimulating hormone and locally high testosterone.

Definition

Testicular function is the dual endocrine and gametogenic activity of the testis: Leydig-cell production of testosterone driven by LH, and Sertoli-cell support of spermatogenesis driven by FSH together with intratesticular testosterone, regulated by feedback on the hypothalamic-pituitary axis.

Scope

This topic covers the endocrine compartments of the testis, the biosynthesis and actions of testosterone, and how LH and FSH together regulate steroidogenesis and spermatogenesis. It also notes feedback signals such as inhibin. It is a reference description of normal physiology, not clinical guidance.

Key concepts

• Leydig cells and LH-driven steroidogenesis
• Sertoli cells and FSH
• Testosterone biosynthesis from cholesterol
• Intratesticular testosterone and spermatogenesis
• 5-alpha-reduction to dihydrotestosterone
• Aromatisation of testosterone to estradiol
• Inhibin and negative feedback on FSH

Mechanisms

Luteinizing hormone binds receptors on Leydig cells and stimulates the conversion of cholesterol, through a series of steroidogenic enzymes, into testosterone; the rate-limiting and enzymatic steps of this pathway were defined by work on steroid biosynthesis. Follicle-stimulating hormone acts on Sertoli cells, which create the environment that supports developing germ cells. Spermatogenesis depends on both signals, with high local concentrations of testosterone within the seminiferous tubules being essential; reviews of the endocrine regulation of spermatogenesis describe the largely independent yet complementary roles of testosterone and FSH. In target tissues, testosterone may act directly, be reduced to the more potent dihydrotestosterone, or be aromatised to estradiol. Sertoli-cell inhibin provides selective negative feedback on pituitary FSH secretion.

Clinical relevance

These mechanisms underpin how male reproductive physiology is understood, including the dependence of sperm production on an intact pituitary-testis axis and adequate intratesticular androgen. The conversion of testosterone to dihydrotestosterone and to estradiol explains why a single secreted hormone has tissue-specific effects. This entry describes physiology and the basis of evidence and does not provide diagnostic or treatment recommendations.

History

The biochemical pathway from cholesterol to testosterone was assembled through twentieth-century steroid chemistry and later clarified at the molecular level. In parallel, endocrine physiology established the division of labour between LH-driven Leydig-cell steroidogenesis and FSH-supported, testosterone-dependent spermatogenesis, and identified inhibin as the Sertoli-cell signal that selectively restrains FSH.

Key figures

• Walter Miller
• David de Kretser
• Robert McLachlan

Seminal works

• miller-1988
• mclachlan-1996
• ramaswamy-2014

Frequently asked questions

What controls testosterone production?

Luteinizing hormone from the pituitary stimulates Leydig cells to synthesise testosterone from cholesterol, and circulating testosterone feeds back to restrain the hypothalamic-pituitary axis.

Why is testosterone important for sperm production?

Spermatogenesis requires high concentrations of testosterone within the seminiferous tubules, acting together with FSH on Sertoli cells to support developing germ cells.