Lesions of the Suprachiasmatic Nucleus Indicate the Presence of a Direct Vasoactive Intestinal Polypeptide‐Containing Projection to Gonadotrophin‐Releasing Hormone Neurons in the Female Rat

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Abstract
In non‐seasonal breeders like the rat, the influence of the suprachiasmatic nucleus (SCN) on reproduction is most clearly expressed in the female. Complete lesions of the SCN induce persistent oestrus (anovulation) in intact female rats, whereas oestrogen implantation in ovariectomized rats results in daily luteinizing hormone surges. Vasoactive intestinal polypeptide (VIP), a peptide synthesized in cell bodies of the SCN, inhibits the increase in pulsatile luteinizing hormone release observed in ovariectomized female rats. In search of the anatomical basis for these observations, the present study employs an immunocytochemical double staining for VIP and gonadotrophin‐releasing hormone (GnRH) at the light microscopical level. It was demonstrated that approximately 45% of the GnRH positive neurons in the diagonal band of Broca, the preoptic and anterior hypothalamic area of female rats are innervated by VIP‐containing processes. To investigate whether these VIP‐containing fibres represent a direct projection of the SCN to the GnRH system, unilateral thermic SCN lesions were made.Lesions that unilaterally destroyed the majority of the VIP synthesizing cells in the SCN resulted in at least a 50% decrease of the VIP innervation of GnRH cell bodies at the lesioned side compared to the intact side. Lesions not affecting the VIP synthesizing cell population in the SCN did not change the percentage of GnRH neurons innervated by VIP‐containing fibres, while partial lesions resulted in intermediate effects.These results indicate that the majority of the light microscopical VIP‐containing input on GnRH neurons in the hypothalamus is derived from the SCN. It is suggested that the reported effects of VIP on luteinizing hormone release may, at least in part, be induced via a direct effect of VIP on GnRH cell bodies. This direct SCN‐GnRH pathway provides an anatomical basis for diurnal influences on the regulation of the female reproductive cycle.