Gonadotropin-releasing hormone

Where is it produced and what does it act on?

GnRH is secreted in the arcuate, supraoptic, and paraventricular nuclei of the hypothalamus.

It reaches the adenohypophysis via a humoral pathway through a specific portal vascular system. This network ensures two-way information transfer between the hypothalamus and the pituitary gland.

In the pituitary gland, the hormone acts on gonadotrophs, stimulating the release of two gonadotropic hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Because of this property, the single term gonadotropin-releasing hormone (GnRH) is used, which is a synonym for luliberin; follicle-stimulating releasing hormone has not yet been isolated.

Next, LH and FSH regulate the function of the gonads:

• In males: LH stimulates Leydig cells, which produce testosterone; FSH stimulates Sertoli cells, which produce androgen-binding protein.
• In females: FSH stimulates follicular growth and estrogen secretion, while the ovulatory LH surge serves as the direct trigger for ovulation.

Mechanism of secretion

The secretion of GnRH is genetically programmed and has a pulsatile (circchoral) character.

Peaks of enhanced secretion last for a few minutes and are followed by intervals of low activity. The arcuate nuclei generate a signal with a frequency of approximately 1 pulse every 1–3 hours.

The frequency and amplitude of GnRH pulses determine which hormone is predominantly secreted by the adenohypophysis—LH or FSH. This causes morphological and secretory changes in the ovaries.

What regulates gonadoliberin production?

• Negative feedback: estrogens suppress the production of gonadoliberin and FSH; testosterone produced by Leydig cells suppresses secretion in the hypothalamus and pituitary gland.
• Neurotransmitters:
• Stimulate GnRH release: norepinephrine, acetylcholine, $\gamma$-aminobutyric acid (GABA).
• Inhibit GnRH release: dopamine, serotonin.
• Neuropeptides: endogenous opioid peptides, corticotropin-releasing factor, and galanin influence hypothalamic function.
• Higher CNS centers: psychoemotional factors can influence reproductive function; the cortex and subcortical structures synthesize neurotransmitters and neuropeptides that affect the hypothalamus.

Clinical significance and use of analogues

• GnRH analogues (agonists) (triptorelin, goserelin, leuprolide, buserelin) form a separate group due to their chemical structure resembling the natural releasing hormone. They are used for the medical suppression of central precocious puberty (CPP), as well as in the treatment of uterine fibroids and preoperative preparation for certain forms of endometriosis.
• Uterine fibroids: GnRH agonists reduce the volume of myomatous nodes by up to 55%. After discontinuation, menstrual function is restored; in some patients, expansive growth of the myoma with signs of impaired nutrition begins.
• Preoperative preparation for myoma: GnRH agonists reduce intra- and perinodular blood flow; the maximum effect is achieved after 2–3 injections.
• Pathologies: impaired dopaminergic regulation of GnRH secretion is involved in the pathogenesis of the central form of polycystic ovary syndrome (PCOS). Impaired migration of gonadoliberin-secreting neurosecretory neurons to the hypothalamus area in congenital forebrain malformations is among the causes of hypogonadism.

Class and exam questions

What else to study on this topic

• Hypothalamo-pituitary system
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Menstrual cycle

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