INVESTIGATION OF THE EFFECTS OF PROGESTERONE ON NEUROPEPTIDE Y-STIMULATED LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETION FROM THE MEDIAN-EMINENCE OF OVARIECTOMIZED AND ESTROGEN-TREATED RATS

We have investigated the hypothesis that administration of progesterone to estrogen-treated ovariectomized (OVX) rats enhances the stimulatory effects of neuropeptide Y (NPY) on the secretion of luteinzing hormone-releasing hormone (LHRH) from median eminence (ME) fragments in vitro. Adult rats were bilaterally OVX and after 2-4 weeks various doses of estrogen were administered subcutaneously in Silastic capsules. Three days later animals were injected subcutaneously with progesterone (1,2 or 19 mg) or oil vehicle. Three hours later animals were killed, trunk blood collected, and the ME dissected and rinsed in culture medium. Incubation medium was collected after 30 min (control) and synthetic porcine NPY (0.1-10 μM) was applied during the test period. LHRH released into the medium and plasma luteinizing hormone were measured with RIA. NPY significantly stimulated LHRH secretion from MEs obtained from estrogen-treated OVX rats injected with oil vehicle. This stimulation was directly dependent on the degreee of estrogen replacement. Administration of physiological doses of progesterone had no effect on NPY-stimulated LHRH release at low physiological levels of estrogen replacement. However, injection of 1 or 2 mg of progesterone into animals receiving the high physiological dose of estrogen slightly, although not significantly, reduced NPY (10 μM)-stimulated LHRH secretion. Treatment with the pharmacological dose of progesterone (19 mg) significantly decreased the ability of NPY to stimulate LHRH release when compared to vehicle-injected controls or to animals receiving 1 mg of progesterone. These results do not support the hypothesis that progesterone enhances NPY-stimulated LHRH secretion. On the contrary, when plasma estrogen levels are similar to those on the afternoon of proestrus, treatment with physiological doses of progesterone slightly attenuates the effects of NPY. Injection of a pharmacological dose of progesterone significantly reduces NPY-stimulated LHRH release in spite of significantly elevated levels of LHRH in the ME. Progesterone may change the sensitivity of LHRH secretory mechanisms in the ME to NPY stimulation on proestrus.