Gonadorelin

Gondaorelin is the natural releasing hormone of the hypothalamus, which stimulates the release of the two gonadotropins follitropin(FSH) and lutropin(LH) from the anterior pituitary gland by activating G-protein-dependent membrane receptors (GnRH receptors). Pharmacologically, native gonadorelin (gonadoliberin) is a basic decapeptide with a hairpin-shaped secondary structure.

The synthetic gonadorelin analogue triptorelin differs from gonadorelin only in the replacement of glycine in position 6 by D-Trp. Leuporelin and buserelin are nonapeptides with D-Leu and tert-butyl-D-Ser respectively, in which the C-terminal glyconamide is additionally replaced by an ethylamino group.

The synthetic gonadorelin analogues have a considerably higher intrinsic activity towards the GnRH receptor (so-called superagonists). They suppress gonadotropin release after transient, initial stimulation by downregulation of the pituitary GnRH receptors.

The competitive synthetic gonadorelin receptor antagonists Cetorelix and Ganirelix are decapeptides in which several positions of native gonadorelin are substituted with C-amino acids. They directly inhibit gonadotropin secretion without initial stimulation. The preparations Abarelix and Degarelix are approved for the therapy of prostate carcinoma.