KiSS-1 peptide induces release of LH by a direct effect on the hypothalamus of ovariectomized ewes

The objectives of this study were: to determine if peripheral administration of the ovine C-terminal decapeptide (oKiSS-1) increases secretion of LH and FSH in ovariectomized (OVX) ewes; to evaluate the effect of ovarian steroid hormones on the predicted increase in gonadotropin secretion induced by oKiSS-1; to establish if the stimulatory effect of oKiSS-1 is due to a direct action on the hypothalamus or was mediated directly at the anterior pituitary gland. Intravenous injection of 3 mg oKiSS-1 to OVX ewes (n = 6) increased (P < 0.01) basal and mean serum concentrations of LH. The amplitude and the area under the curve (AUC) of LH induced by oKiSS-1 was greater (P < 0.01) than the highest pulse of LH detected before oKiSS-1. Pre-treatment with steroid hormones (1 mg progesterone plus 50 μg estradiol-17β for 3 days) in OVX ewes (n = 6) reduced (P < 0.1) the magnitude of the stimulatory effect of oKiSS-1 on LH secretion. In these animals, oKiSS-1 increased (P < 0.1) basal and mean concentrations of LH, and the amplitude of the pulse of LH induced by oKiSS-1, but not the AUC (P > 0.1). In our hands, oKiSS-1 failed to increase serum concentration of FSH at the dose used in this study. Administration of GnRH antiserum completely suppressed the secretory patterns of LH and prevented the increase in secretion of LH induced by oKiSS-1. We conclude that the rapid increase in secretion of LH induced by peripheral administration of oKiSS-1 is the result of a direct action on the hypothalamus.