DOES GONADOTROPIN-RELEASING-HORMONE IN THE CEREBROSPINAL-FLUID MODULATE LUTEINIZING-HORMONE RELEASE

The function of gonadotropin-releasing hormone (GnRH) in the cerebrosp inal fluid (CSF) is unknown. This study on ovariectomized ewes investi gated whether CSF-GnRH has a role in modulating luteinizing hormone (L H) secretion either through an ultrashort-loop feedback system to affe ct GnRH secretion or to directly act on the pituitary gland after ente ring the hypothalamohypophysial portal system. In the first experiment , a 3-hour continuous infusion of exogenous GnRH (700 or 7 pg/min; n = 8) was administered into the third ventricle through a permanent indw elling cannula. Jugular LH concentrations were measured as an estimate of the activity of the GnRH 'pulse generator'. To assess the potentia l for a direct involvement of CSF-GnRH in pituitary stimulation of LH secretion, ewes were also implanted with a cannula to collect hypophys ial portal blood. In a first investigation, radioactive (2 x 10(6) cpm I-125-GnRH; n = 3) GnRH was injected into the third ventricle, and th e amount of radioactivity present in the portal and jugular blood afte r the injection measured. In a second investigation, cold GnRH was inf used (400 pg/min; n = 3) into the third ventricle for 2 h, and portal and jugular blood collected for the determination of GnRH and LH conce ntrations, respectively. In the first experiment, neither rate of infu sion of GnRH into the third ventricle had any effect on the mean inter pulse interval, nadir, pulse amplitude or circulating level of systemi c LH, suggesting that CSF-GnRH is not a component of an ultrashort-loo p feedback system for GnRH. Furthermore, in the second experiment, des pite extremely low levels of radioactivity (maximum: 120 cpm/ml) being detected in hypophysial portal blood (which may not have been intact decapeptide), in the second part of this experiment, no radioimmunoass ayable GnRH associated with the period of infusion could be measured. These data demonstrate in ewes that little, if any, CSF-GnRH reaches t he hypophysial portal blood, and this compartment of GnRH does not, th us, directly affect the pituitary gland. The present study strongly su ggests, therefore, that CSF-GnRH does not modulate LH secretion. Wheth er this compartment of GnRH is involved in sexual behavior remains to be established.