Leptin as the permissive energy signal for puberty
Leptin, a hormone from fat cells, tells the hypothalamus that energy stores are adequate, a permissive signal (it allows puberty to go ahead without being the trigger).
Remember
Leptin tells the hypothalamus that energy stores are adequate, which permits release of gonadotrophin-releasing hormone (GnRH), the hypothalamic signal that starts puberty. It allows puberty to go ahead but is not the trigger itself.
Leptin is a protein hormone that adipocytes (fat cells) make, and its level in the blood relates to how much fat the body stores. Like a fuel gauge, it reports energy reserves to the hypothalamus, the part of the brain that controls the pituitary gland, and there it inhibits hunger.
Reproduction is energetically costly, so the brain waits for enough fuel before the reproductive axis switches on. That axis is the hypothalamus, the pituitary gland and the gonads (the testes or ovaries) working together. Leptin is permissive: it allows GnRH release to go ahead but is not the trigger itself. GnRH is released in pulses and makes the anterior pituitary gland secrete luteinising hormone (LH) and FSH, which act on the gonads to make sex hormones. Because reproduction is energetically costly, the start of puberty follows body composition and nutrition.
Leptin can also act on GnRH release separately from the usual sex steroid feedback loop, the negative feedback that normally restrains the reproductive axis. When leptin is low because body fat is very low, GnRH release is suppressed, so puberty is delayed or periods stop. In congenital leptin deficiency, leptin is very low despite a large fat mass, severe obesity develops from early childhood, and puberty may fail to start. Without the permissive signal, GnRH drive falls, so the pituitary gland releases little LH and FSH and the gonads make few sex hormones. This is hypogonadotropic hypogonadism. Hypogonadism means low sex hormone production, and hypogonadotropic means that low gonadotropins (LH and FSH) come with it, which points to the brain rather than the gonads.
Key facts
- Where it comes from
- fat cells (adipocytes) release it in relation to the body's fat mass.
- Type of hormone
- a protein hormone, not a steroid and not a gut or pituitary hormone.
- What it does
- it suppresses hunger and acts as a permissive signal that lets GnRH-driven puberty go ahead.
- Not the trigger
- it permits puberty once energy stores are adequate but it does not decide the moment of onset.
- Low leptin
- very low body fat, as in undernutrition, keeps leptin low, which suppresses GnRH release and delays puberty or stops periods.
- If it is missing
- congenital leptin deficiency causes severe obesity from early life, and puberty may fail to start when leptin signalling is absent.
Exam traps
- Failure of the gonads does not explain delayed puberty with low LH and FSH, because gonadal failure removes negative feedback and so makes LH and FSH rise; low levels point above the gonads, to the hypothalamus or pituitary, and in leptin deficiency to the hypothalamic drive that leptin normally permits.
- Leptin does not come from the gut and does not itself delay puberty: it is made by fat cells and permits puberty rather than delaying it.
- A fall in body fat does not release GnRH: low leptin, as with very low body fat, keeps GnRH release low and so holds puberty back.
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