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The Male HPG Axis: Brain Talks to Testis

GnRH pulses, LH and FSH, and the feedback signals testosterone and inhibin B send back up the line.

A three-floor command chain

The testis does not act alone. It takes orders from the brain through the hypothalamic-pituitary-gonadal axis — an endocrine axis with three floors. The top floor is the hypothalamus, the middle floor is the anterior pituitary, and the ground floor is the testis. Each floor sends a chemical message down to the next, and the bottom floor sends signals back up so the whole system stays balanced.

The starting signal is GnRH, released by the hypothalamus. A crucial detail: GnRH is not poured out steadily but in sharp bursts — pulsatile secretion, roughly one pulse every one to three hours. This rhythm is the secret password. If GnRH were given as a constant infusion instead of pulses, the pituitary would actually shut down — a quirk that becomes a useful drug strategy later in this track.

LH and FSH: two messengers, two targets

Each pulse of GnRH tells the pituitary to release two hormones: LH (luteinizing hormone) and FSH (follicle-stimulating hormone). Their names come from the female cycle, but in men they have clean, separate jobs. LH travels to the Leydig cells and tells them to make testosterone. FSH travels to the Sertoli cells and tells them to support sperm production.

Feedback: how the testis answers back

The system keeps itself steady through negative feedback. When testosterone rises, it travels back to the hypothalamus and pituitary and tells them to *slow down* GnRH and LH. As testosterone falls, the brake releases and LH climbs again. This is a classic feedback loop holding testosterone near a set point.

But testosterone only controls the LH arm. The FSH arm has its own brake: inhibin B, a hormone made by Sertoli cells when sperm production is healthy. Inhibin B feeds back to suppress FSH. This gives the body two independent dials — one watching the hormone (testosterone → LH) and one watching the sperm factory (inhibin B → FSH). Doctors lean on this split: a high FSH with a low inhibin B points the finger at a failing sperm factory specifically.

GnRH pulse (hypothalamus)
   |  every 1–3 h
   v
Anterior pituitary --> LH ----> Leydig cell --> TESTOSTERONE
                   --> FSH ----> Sertoli cell --> sperm + INHIBIN B

Feedback brakes:
   TESTOSTERONE --(-)--> hypothalamus & pituitary  (slows GnRH/LH)
   INHIBIN B    --(-)--> pituitary                 (slows FSH only)
The male HPG axis: two outputs (testosterone, sperm) with two separate feedback brakes.