DIRECT ANTERIOR-PITUITARY MODULATION OF GONADOTROPIN-SECRETION BY NEUROPEPTIDE-Y - ROLE OF GONADAL-STEROIDS

Neuropeptide Y (NPY) acts at the hypothalamus to stimulate LH secretio n through increased LHRH secretion. NPY is also cosecreted into the po rtal system in a pulsatile manner with LHRH and may act at the anterio r pituitary to increase LH secretion through potentiation of LHRH resp onsiveness and possibly through direct stimulation; however, controver sy exists concerning this direct action of NPY at the pituitary. Utili zing dispersed anterior pituitary monolayer cell cultures, the first g oal of this study was to determine the effects of vehicle, 10(-10) M L HRH, 10(-7) M NPY, 10(-6) M NPY, 10(-10) M LHRH + 10(-7) M NPY, and 10 (-10) M LHRH + 10(-6) M NPY on LH and FSH responsiveness. Under these conditions, 10(-6) M NPY alone significantly stimulated LH secretion ( 630% above basal) and both 10(-7) M NPY and 10(-6) M NPY significantly potentiated LHRH-induced LH secretion (195 and 244% above LHRH alone, respectively). Neither 10(-7) M NPY nor 10(-6) M NPY alone stimulated FSH secretion; however, both 10(-7) M and 10(-6) M NPY significantly potentiated LHRH-induced FSH secretion (130 and 135% above LHRH alone, respectively). The second goal of this study was to determine whether the gonadal steroid conditions prevailing prior to the preovulatory g onadotropin surge play a role in modulating NPY responsiveness; this e xperiment utilized anterior pituitary (AP) halves from immature ovarie ctomized estrogen + progesterone (E + P) primed female rats to determi ne the role of gonadal steroids in the LH and FSH response to vehicle, 10(-8) M LHRH, 10(-7) M NPY, 10(-6) M NPY, 10(-8) M LHRH + 10(-7) M N PY, 10(-8) M LHRH + 10(-6) M NPY. Under these conditions, data indicat ed that NPY alone did not significantly stimulate LH secretion in this animal model. However, LHRH-induced LH release was potentiated by 10( -6) M NPY in vehicle, estrogen (E), and estrogen + progesterone primed groups (240, 160 and 200% above LHRH alone, respectively), while 10(- 7) M NPY potentiated LHRH-induced LH release only in the estrogen and estrogen + progesterone primed groups (150 and 170% greater than LHRH alone, respectively). Estrogen + progesterone did not significantly in crease the magnitude of NPY potentiation above that observed in the es trogen only group. NPY alone did not stimulate FSH secretion in any gr oup. Neither estrogen alone nor estrogen + progesterone had any effect on FSH responsiveness to NPY or LHRH alone; neither estrogen alone no r estrogen + progesterone potentiated LHRH-induced FSH secretion. Thes e studies demonstrated that in dispersed AP cell cultures derived from intact random cycle rats, NPY was capable of acting either alone to s timulate LH secretion or in combination with LHRH to potentiate both L H and FSH secretion. When the immature ovariectomized E + P-primed rat model was employed, these studies demonstrated that estrogen alone in the absence of progesteron (P) was sufficient to maximize LH responsi veness to NPY + LHRH, thereby indicating that P probably acts at the h ypothalamus in vivo to induce the gonadotropin surge observed in this model. The data support the hypothesis that NPY is a physiologically s ignificant modulator of gonadotropin secretion.