GnRH II and type II GnRH receptors.

Hypothalamic gonadotrophin-releasing hormone (GnRH I), which is of a variable structure in vertebrates, is the central regulator of the reproductive system through its stimulation of gonadotrophin release from the pituitary. A second form of GnRH (GnRH II) is ubiquitous and conserved in structure from fish to humans, suggesting that it has important functions and a discriminating receptor that selects against structural change. GnRH II is distributed in discrete regions of the central and peripheral nervous systems and in nonneural tissues. The cognate receptor for GnRH II has recently been cloned from amphibians and mammals. It is highly selective for GnRH II, has a similar distribution to GnRH II in the nervous system and, notably, in areas associated with sexual behaviour. It is also found in reproductive tissues. An established function of GnRH II is in the inhibition of M currents (K(+) channels) through the GnRH II receptor in the amphibian sympathetic ganglion, and it might act through this mechanism as a neuromodulator in the central nervous system. The conservation of structure over 500 million years and the wide tissue distribution of GnRH II suggest that it has a variety of reproductive and nonreproductive functions and will be a productive area of research.