Hypothalamic–pituitary–gonadal axis (HPG axis)

The hypothalamic–pituitary–gonadal axis is an integrated neuroendocrine system comprising the hypothalamus, pituitary gland, and gonads (ovaries/testes)[1][3][4][7]. The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH)[3][4][5]. These pituitary gonadotropins act on the gonads, promoting the synthesis of sex steroid hormones (estrogen, progesterone, testosterone) required for development, puberty, fertility, and overall reproductive function[1][3][4][5]. The HPG axis is regulated by feedback loops involving sex steroids and other regulatory peptides such as inhibin and anti-Müllerian hormone (AMH)[4][6]. Disorders affecting this axis manifest as reproductive and endocrine diseases such as hypogonadism, infertility, precocious or delayed puberty, and menopausal symptoms[4][6]. Pharmacological agents targeting this axis typically act by modulating hormone production or action at various points in the pathway[2][6]. The axis is not itself a druggable molecular entity, but its individual receptors and hormones (e.g., GnRH receptor, LH/FSH receptors) are bona fide molecular drug targets[3][4][6].

Other names

pituitary gonadotropin axishypothalamic-pituitary-gonadal axisHPG axishypothalamic-pituitary-ovarian axis (in females)hypothalamic-pituitary-testicular axis (in males)

Blockade or stimulation of GnRH secretion or receptor signaling, Agonism/antagonism at gonadotropin receptors, Supplementation with exogenous hormones