NATURE AND BIOACTIVITY OF GONADOTROPIN-RELEASING-HORMONE (GNRH) SECRETED DURING THE GNRH SURGE

Previous studies have demonstrated a neural action of estradiol in ind ucing a surge of GnRH in the ewe. However, although the GnRH and LH su rges began concurrently, the GnRH surge consistently continued well be yond the surge of LH. Three experiments were conducted to test the hyp othesis that the termination of the LK surge results from the secretio n of a relatively inactive variant of GnRH during the later phases of the GnRH surge. In the first experiment, hypophyseal portal blood coll ected during an estrogen-induced LH surge was analyzed for GnRH immuno reactivity using two antibodies having specificity for the N- or C-ter minal portion of the GnRH molecule. The duration, amplitude, and time course of the GnRH surge were found to be similar irrespective of the antisera used. In a second experiment, a competitive GnRH antagonist w as administered at the beginning of the estrogen-induced GnRH/LH surge at a dose capable of blocking pituitary responsiveness for approximat ely half the duration of the GnRH surge. Antagonist treatment did not result in any change in the time of onset of the GnRH surge, but there was no increase in LH that naturally occurs coincident with onset of the GnRH surge. Rather, a persistent increase in LH secretion was obse rved during the latter stages of the GnRH surge, indicating that the G nRH molecules secreted at this time were biologically active. Finally, a sensitive and specific ovine pituitary cell bioassay was used to te st bioactivity of GnRH in hypophyseal portal blood during different ph ases of the GnRH surge. GnRH bioactivity in samples collected early in the GnRH surge was greater than that before the onset of the GnRH sur ge but no greater than that collected during the descending Limb of th e surge. The results of all three experiments fail to support the hypo thesis that the LH surge ends because of a change in the nature of the GnRH secreted. Rather they show that GnRH secreted throughout the sur ge is biologically active. Thus, the termination of the LH surge befor e that of the GnRH surge occurs for reasons other than lack of a bioac tive GnRH signal.