GnRHneuroner

GnRH neurons, or gonadotropin-releasing hormone neurons, are specialized neuroendocrine cells that synthesize and secrete the decapeptide GnRH. They form a key link between the brain and the reproductive endocrine axis, regulating the release of pituitary gonadotropins in response to pulsatile GnRH signaling.

In mammals, GnRH neurons are primarily located in the preoptic area and hypothalamus. They originate in the olfactory placode during development and migrate into the hypothalamus, a process that can be disrupted in conditions such as Kallmann syndrome. Humans have a relatively small, widely distributed population of GnRH neurons, estimated in the low thousands.

GnRH is released in a pulsatile fashion into the hypophyseal portal system, where it stimulates the anterior pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The frequency and amplitude of GnRH pulses help determine the relative secretion of LH and FSH, with faster pulse frequencies generally favoring LH release.

The GnRH pulse generator is regulated by a network of neurons, notably the kisspeptin-producing population (KISS1) and the neurokinin B/dynorphin (KNDy) system in the arcuate nucleus. Feedback from gonadal steroids (testosterone, estradiol, progesterone) modulates GnRH activity. External factors such as energy balance, stress, and photoperiod can also influence pulsatility and reproductive timing across species.

Clinically, GnRH neuron function is central to disorders of puberty and reproduction. Mutations affecting GnRH signaling or neuron migration can cause congenital hypogonadotropic hypogonadism, often with anosmia (Kallmann syndrome). Therapeutically, GnRH agonists or antagonists are used to regulate fertility, manage precocious puberty, endometriosis, and prostate cancer; pulsatile GnRH therapy supports fertility, while continuous administration suppresses the reproductive axis.