Prenatal development of the gonadotropin-releasing hormone-containing systems in rat brain.

Pre-embedding immunofluorescence was used to study the development of the gonadotropin-releasing hormone (GnRH)-containing neuronal systems in the brain of fetal and newborn rats. Immunoreactive cell bodies are first seen in association with the ventral olfactory bulb at the fetal embryonic (E) day 15. At day E 17, single GnRH-containing neurons are found in the nasal system, along the olfactory nerve, in the ganglion terminale, olfactory bulb, septum-diagonal band complex, olfactory tubercle and in the ventrolateral hypothalamus. A major spurt in the development of the brain GnRH-containing systems occurs between days E 18 and E 19. At day E 19, immunoreactive cell bodies are present in all areas as in the adult animals, however, in smaller number. GnRH-containing fibers are first detected in the nasal system at day E 17. At day E 18, GnRH positive projections are present in the nervus terminalis, in the developing organum vasculosum of the lamina terminalis and ventral hypothalamus. By day E 19, GnRH containing connections are established with most of the final target areas. These areas include the caudal olfactory bulb, lateral septum, stria terminalis, fimbria hippocampi, habenula, supramammillary commissure and central gray. In the hypothalamus, 3 major pathways are recognized: a ventral projection which runs in and beneath the optic chiasm toward the median eminence; a ventrolateral tract which is located lateral to the optic chiasm and which projects along the optic tract toward the lateral thalamus as well as to the median eminence; a periventricular network which projects to the habenula and, in a caudal direction, to the mediobasal hypothalamus including the median eminence. The results of the present study suggest that the GnRH neuronal systems develop considerably earlier than previously reported and that the intracerebral GnRH-containing fiber connections are established several days before birth.