GnRH and steroids in cancer

Abstract

Gonadotropin-releasing-hormone (GnRH) analogues are synthetic compounds derived from decapeptide neurohormones (LHRH; LH/FSH-RH). They have a key role in hormone dependent cancer, particularly breast and prostate cancer. GnRH analogues produce an efficient inhibition of gonadotropins and sex steroid hormones. Their use in cancer therapy result in a, pharmacological castration (i.e. ovariectomy and orchiectomy), providing an androgen and estrogen ablation. GnRH exert an inhibitory action on the growth of hormone-dependent human and canine mammary tumor. Mammary tumors can produce growth factor that potentially could modulate their own proliferation in an autocrine fashion (i.e. TGF-alpha and TGF-beta or with a paracrine mechanism (i.e. EGF, IGF, FGF). The expression of EGF receptors is related in mammary tissues to the action of oestrogen and progesteron and to the presence of functional receptors for oestrogen (ER) and progesteron (PR). The present review elucidate the role of GnRH receptors in cancer and their connection with steroid hormones. Besides we showed the link between GnRH and signal transductions pathways: Estrogen-receptors, GnRH-receptors, EGF-receptors signal transduction pathways. A very tight link exists between steroid hormones and GnRH analogues both on central pituitary gonadal axis and on tumor receptors peripherically. This last mechanism could be explained either locally activating GnRH receptors or locally interacting with EGF receptor-Intracellular NitricOxide system.

Leuprorelin acetate affects ERK1/2 activity in prostate cancer cells

“…In particular, they have been investigated for their therapeutic advantages in hormone-related tumors. GnRH agonist administration results in hormone ablation (chemical castration) which can effectively replace surgical castration (2). The slowing-down of neoplastic cell growth is based on the reduction of sex steroid supply (3).…”

“…In addition, it is widely accepted that GnRH analogues may act directly on tumor cells via specific receptors expressed on cell membrane. Several reports have provided evidence that GnRH analogues negatively control the proliferation of breast, ovarian, endometrial and prostate cancer cells (2). Nevertheless, the mechanisms that underlie this direct action are poorly understood.…”