Modulation of proliferation by gonadotropin-releasing hormone receptors in breast cancer cells

Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic neurons and bind to receptors on gonadotrope cells of the pituitary gland, which then synthesize and release luteinizing hormone and follicle-stimulating hormone that regulate gonadal development. The presence of GnRH receptors and the effects of synthetic analogs of GnRH at extrapituitary sites is less clear. Several reports suggest that GnRH/analogues through cognate receptors may regulate mitogenic responses in cancer cells in an autocrine or paracrine manner. However, the inherent intracellular signaling pathways triggered are unknown. Using a highly specific antibody to human GnRH receptor we show that T47D breast cancer cells express GnRH receptors on their surface and that a GnRH analogue Cetrorelix inhibits proliferation of these cells, possibly via inhibition of processes that trigger cAMP formation.