Physiology of Testes and Endocrine Functions

Physiology of Testes

• Testes contain seminiferous tubules lined with Sertoli cells and interstitial Leydig cells.
• Sertoli cells nourish developing sperm and secrete growth factors.
• Sertoli cells create a blood-testis barrier.
• Sertoli cells secrete androgen-binding protein (ABP).
• Leydig cells synthesize and secrete testosterone (T).
• Maintaining a temperature 2°C below body temperature is crucial for spermatogenesis.
• Testosterone production: ~7 mg/day
• Testosterone is mostly bound to albumin and sex hormone-binding globulin (SHBG).
• Cholesterol is converted into pregnenolone.

Endocrine Roles

• Testosterone (T) is produced primarily in the testes.
• Luteinizing hormone (LH) stimulates Leydig cells to produce testosterone.
• Testosterone and follicle-stimulating hormone (FSH) initiate and maintain spermatogenesis.
• Dihydrotestosterone (DHEA) is a more potent form of testosterone created from T.
• DHT is produced by 5-alpha reductase and can be found in skin, prostate, and other genital tissues.
• Aromatase converts testosterone to estradiol (E2) in some tissues.
• These hormones mediate development of male secondary sexual characteristics and spermatogenesis.

Androgen Actions

• Testosterone and DHT bind to intracellular androgen receptors.
• This binding alters transcription, stimulating growth and function of accessory reproductive organs.
• Testosterone promotes development of male internal genitalia, spermatogenesis, muscle mass, and libido.
• DHT contributes to development of external genitalia, prostate enlargement, facial hair, and acne.

Hypothalamic-Pituitary-Gonadal Axis

• Gonadotropin-releasing hormone (GnRH) is released in pulses every 3 hours from the hypothalamus.
• GnRH stimulates the release of LH and FSH from the pituitary.
• LH stimulates Leydig cells to produce testosterone (T).
• FSH stimulates Sertoli cells to support spermatogenesis.
• The production of T and FSH follows a negative feedback loop, where testosterone and inhibin regulate GnRH and LH release.

Ducts and Accessory Glands

• Seminal vesicles contribute about 12 volume units to semen.
• The prostate releases about 20% of semen volume.
• Semen contains sperm, mucus, water, buffers, nutrients (fructose, citric acid, vitamin C, carnitine), enzymes, and zinc.
• Prostaglandins from the seminal vesicles might help with sperm transport or fertilization.

Sperm

• Average sperm concentration is 100 million/mL.
• Low fertility: 20-50 million/mL; infertility: <20 million/mL.

Pathophysiology (e.g., Androgen Insensitivity Syndrome)

• Androgen insensitivity syndrome (AIS) : mutations in the androgen receptor cause XY individuals to present as females, or with ambiguous genitalia.
• Differently mutated androgen receptor forms lead to various clinical presentations.
• Actions of estradiol in males: necessary for fertility, bone density, etc.

Related Conditions

• Hypogonadism: impaired testicular function; categorized into primary (hypergonadotropic), involving reduced T levels with elevated FSH/LH, and secondary (hypogonadotropic).
• Klinefelter syndrome (XXY) is a common example of primary hypogonadism, characterized by reduced testosterone and elevated FSH/LH.
• 5-alpha reductase type 2 deficiency: the body cannot convert testosterone into DHT, can lead to ambiguous genitalia at birth and is often assigned female at birth (but not always).

Prostate Cancer

• Prostate cancer is often related to mutations in the androgen receptor, marked by elevated PSA levels.
• Prostate-specific antigen (PSA) is a marker used to monitor prostate cancer.