Determination of the Characteristic of the GnRH Surge Generator by Multifarious Approaches

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A series of multifarious experiments was performed in female rats to determine the characteristic of the gonadotropin-releasing hormone (GnRH) surge generator which had been evidenced, by us, to be the neural mechanism distinct from that the GnRH pulse generator and the following results were obtained.1. To determine whether the suprachiasmatic nucleus (SCN) will drive a circadian release of GnRH in the rat preoptic area (POA), we measured the release of GnRH, arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in cocultures of the preoptic area and the SCN at 2-h intervals over a period of 120 h. The release of GnRH in cocultures exhibited a significant circadian rhythm in the presence of estrogen but not in the absence of estrogen. The period of GnRH circadian rhythm was the same as that of the AVP rhythm, and different from the VIP circadian rhythm in each coculture. Furthermore, the peak phase of the GnRh rhythm occurred at the time same as that of the AVP in eac … More h culture, but was not always the same as that of the VIP rhythm. The results demonstrated that these in vitro cocultures can be used as an experimental model for the GnRH surge generator and that AVP neurons in the SCN mediate the clock information to GnRH surge generator in the POA.2. To determine whether the AVP V1 receptor antagonist will affect the surge secretion of LH, we injected it into the third ventricle in the proestrous rat and measured serum concentrations of LH between 1100 and 2100 h. The injection of AVP receptor antagonist at 1300 h resulted in a significant decrease in LH secretion compared to saline-injected control rats, supporting evidence our hypothesis that endogenous AVP plays a role in the induction of the surge of LH secretion.3. To determine whether the surge generator involves the Na ion channel-dependent mechanism, we injected TTX into both sides of the POA at 1300 h in the proestrous rat and measured serum concentrations of LH at 1-h intervals. The injection of TTX did not induce any significant effect in LH secretion compared to saline-injected control rats, suggesting that the GnRH surge generator releases GnRH with mechanisms different from Na ion channels-dependent ones. Less