ORCHIECTOMY AND NMDA INCREASE GNRH SECRETION AS MEASURED BY PUSH-PULLPERFUSION OF RAT ANTERIOR-PITUITARY

Using push-pull perfusion to measure concentrations of gonadotropin-re leasing hormone (GnRH) in the extracellular fluid of the anterior pitu itary gland of the male rat, we have measured GnRH release at specific times before and after castration and in response to acute administra tion of N-methyl-D-aspartate (NMDA). After castration (7 days), mean G nRH levels were subtantially increased (4.3-fold) compared with intact controls (0.94 +/- 0.16 vs. 0.22 +/- 0.08 pg/10 min, respectively, P < 0.05) due to an increase in both the frequency and amplitude of GnRH pulses. Testosterone partially reduced GnRH release (0.62 +/- 0.10 pg /10 min). NMDA induced a rapid increase in plasma luteinizing hormone (LH) in both intact and castrated rats and increased GnRH concentratio ns in the perfusion samples (P < 0.05). There was no change in LH rele ase induced by two doses of injected GnRH (5 and 25 ng/100 g body wt) 2 days after castration, but by 6 days after castration the response t o both doses was significantly increased. These results demonstrate th at GnRH release in the male rat is acutely increased by NMDA and is ch ronically increased after orchidectomy. Increased pituitary sensitivit y to GnRH also contributes to the hypersecretion of LH after castratio n, particularly at longer times after removal of testesterone negative feedback.