Neuropeptide Y (NPY), the most widely distributed neuropeptide in the body, has been localized to all tissues of the reproductive tract in many species, including sheep. NPY has been associated primarily with the control of food intake, and is also known to promote angiogenesis. In the hypothalamic-pituitary axis, NPY facilitates the increase in gonadotrophins associated with seasonal reproductive cyclicity, and can also stimulate the release of oxytocin (OT) from the posterior pituitary. While NPY increases the production of progesterone (P) by dispersed luteal cells in vitro, the effect of NPY on luteal P or OT secretion in vivo has not been determined. In the present study, we investigated in vivo the action of NPY on the secretion rate (SR) of OT and P, and on ovarian blood flow (BF) using sheep with the left ovary autotransplanted to a jugulo-carotid loop. After cannulating the left carotid artery and jugular vein, the application of a pneumatic cuff to the upper loop permits the infusion of NPY directly into the arterial supply of the ovary and the periodic collection of timed samples of ovarian venous blood over ice in the conscious unstressed sheep. Because of the separation of the ovary from the uterus in this model, the corpus luteum (CL) persists for the length of a normal gestation, thus allowing for experimentation on CLs of various ages. The effect of NPY on CLs of different ages is important, because OT content is highest after 5 days, then slowly declines until eventual depletion from the CL by day 24 of the cycle (Biol. Reprod. 40:1215, 1989). Two experiments were designed to investigate the action of NPY on the secretion of OT and P by the CL. In experiment 1, sheep bearing CLs over 30 days of age were infused intra-arterially with either saline (n=3) or NPY (n=3) to determine if NPY affected the SR of P or ovarian BF. In experiment 2, sheep bearing CLs of 11 days of age (n=3) were also infused intra-arterially with NPY, to determine if NPY could affect the SR of OT or P or ovarian BF. In both experiments 1 and 2, NPY was infused sequentially at the following rates: 1ng/min; 10ng/min; 100ng/min; and 1000ng/min; each for a 30 min period with a rest period of 90 min between each infusion rate. Timed samples of ovarian venous blood were collected over ice at −30, −20, −10, and then at +10, +20, +30, +60, and +90 mins for each infusion rate. After centrifugation and separation over ice, plasma was stored at −20°C prior to the measurement of OT and P by ELISA and RIA, respectively. Ovarian BF, SR of P and SR of OT were calculated and analyzed by ANOVA for dose and dose by time interactions. In sheep bearing a CL over 30 days of age, there was a dose dependent increase in BF (P=0.001) and a tendency for an increase in the SR of P (P=0.134). Likewise, in sheep bearing a day 11 CL ovarian BF increased (P=0.026), but the SR of P was not changed (P=0.40). Importantly, in the day 11 sheep, NPY significantly increased the SR of OT in a dose-dependent manner (P=0.026). Collectively, these findings suggest that, in the ovine CL, NPY may play a direct or indirect role in the release of luteal OT and in the regulation of ovarian blood flow, and to a lesser extent may influence the SR of P. These effects of NPY appear to be affected by both age and dose-dependent mechanisms and, as such, they may be important around the time of luteolysis or implantation (Supported by USDA Grant # 2004–35203–14176). (poster)