Frequency Modulation of Pulsatile Luteinizing Hormone-Releasing Hormone Stimulation Can Alter the Effectiveness of Direct Androgen Feedback on Luteinizing Hormone-Releasing Hormone-Induced Luteinizing Hormone Release*

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Abstract
A previous study in phenobarbital-treated male rats (1) indicated that both orchidectomy and dihydrotestosterone (DHT) treatment could act directly on the pituitary to modify LH release in response to infused LHRH. These feedback effects did not modify the initial phase of the response to LHRH but became evident during the phase of augmented LH release which began between 60–120 min after the onset of the LHRH stimulus, presumably as a result of LHRH self-priming during the first hour. The present study was done to determine whether similar results would be obtained if LHRH was administered as a series of pulses instead of by continuous infusion. Male rats with iv cannulae were given phenobarbital, then castrated, and immediately given DHT or control implants sc. Three hours later, each rat was given the first of a series of hourly or half-hourly LHRH injections via the cannula. As with LHRH infusion, the initial responses to LHRH were not modified by the presence or absence of DHT. Development of augmented responsiveness, which became evident during the second hour of exposure to either LHRH regimen, was also uninfluenced by DHT in the rats exposed to hourly LHRH injections. However, in rats given half-hourly LHRH injections (which induced periodic LH spikes at a frequency close to that of the endogenous LH rhythm in the orchidectomized rat), DHT did reduce the magnitude of the ultimate response. With all four DHT-LHRH regimens, the level of pituitary responsiveness which had developed by 2 h after the initial LHRH injection was maintained unchanged thereafter, in one experiment through 15 additional h. With pulsatile LHRH administration, pulse frequency can determine whether the rapid direct androgen feedback mechanism dealt with in these studies will or will not influence LH release. This finding suggests that frequency modulation of an endogenous LHRH rhythm might play a role in the feedback regulation of LH secretion. Whether the endogenous LHRH rhythm in the rat is subject to frequency modulation and whether the endogenous LHRH pattern in the intact male rat is one which would allow direct androgen feedback to operate physiologically are questions which remain to be investigated.