The activity of Leydig cells is tightly regulated by the hypothalamic-pituitary-gonadal axis. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary gland to secrete LH. LH, in turn, binds to receptors on Leydig cells, activating pathways that lead to the synthesis and release of testosterone. Negative feedback mechanisms involving testosterone and other hormones help maintain homeostasis.