Gonadotropin-Releasing Hormone (GnRH)

GnRH, or Gonadotropin-Releasing Hormone, is a master hormone produced by the hypothalamus in the brain. It plays a central regulatory role in the body’s reproductive system by controlling the release of two critical hormones from the pituitary gland:

• Luteinizing Hormone (LH)
• Follicle-Stimulating Hormone (FSH)

These two hormones then act on the gonads — the ovaries in women and the testes in men — to regulate fertility, sex hormone production, and sexual development.

🧠 How Does GnRH Work?

📍 Origin:

GnRH is secreted in pulses from the hypothalamus and travels through a special blood vessel system (the hypophyseal portal system) to the anterior pituitary gland, where it stimulates the release of:

• LH (Luteinizing Hormone)
• FSH (Follicle-Stimulating Hormone)

These hormones are then released into the bloodstream to act on reproductive organs.

🧬 What Does GnRH Do?

In Women:

• Stimulates LH and FSH, which:
  • Trigger follicle development
  • Cause estrogen and later progesterone production
  • Control ovulation and menstrual cycles

In Men:

• Stimulates LH, which tells Leydig cells in the testes to produce testosterone
• Stimulates FSH, which helps support sperm production

🔁 Pulsatility Matters

The frequency and rhythm of GnRH pulses are essential:

• Normal pulsatile release → Maintains proper LH/FSH balance and fertility
• Constant, non-pulsatile release → Paradoxically suppresses LH and FSH

This principle is important in medical treatments, as we’ll see below.

🧪 Clinical Uses of GnRH (and GnRH analogs)

✅ GnRH Stimulation Test

• Used to diagnose problems with puberty, pituitary function, or fertility

✅ GnRH Agonists (mimic GnRH but overstimulate to suppress the system over time):

Used to suppress reproductive hormone production in conditions like:

• Prostate cancer (in men — lowers testosterone)
• Endometriosis and uterine fibroids (in women — lowers estrogen)
• Precocious puberty (early puberty — slows it down)
• Transgender hormone therapy (to suppress natural sex hormone production)

Examples: leuprolide (Lupron), goserelin (Zoladex), triptorelin

✅ GnRH Antagonists (block GnRH receptors directly):

Used when rapid hormone suppression is needed, often in situations like advanced prostate cancer.

⚠️ Disorders Involving GnRH:

📉 Low GnRH Production:

• Kallmann syndrome: Genetic condition causing delayed or absent puberty (often with no sense of smell)
• Hypothalamic amenorrhea: Seen in athletes, eating disorders, or severe stress — causes missed periods and infertility
• Hypogonadotropic hypogonadism: Low sex hormones due to pituitary/hypothalamic dysfunction

📈 Excess GnRH (rare):

• Often due to a GnRH-secreting tumor (rare)
• Can cause precocious puberty in children

🔬 Summary Table: