In vivo and in vitro examination of an autoregulatory mechanism for luteinizing hormone-releasing hormone.

Recent evidence has been presented that demonstrates the existence of ultrashort feedback circuits for a number of neuropeptides in the central nervous system. The present investigation was undertaken to examine the possible existence of an autoregulatory mechanism for LHRH. In the first experiment, long term ovariectomized rats bearing lateral ventricular and atrial cannulae received intracerebroventricular (icv) injections of saline or LHRH every hour from 1200-1500 h. Blood was collected at 10-min intervals from 1200-1500 h to assess the effects of icv LHRH on pulsatile LH and FSH release. After the 1500 h collection, LHRH was injected iv and blood was collected to determine the effects of icv LHRH on pituitary responsiveness to LHRH. Central injections of 0.1 pg and 1 ng LHRH, but not 10 pg LHRH, significantly suppressed mean LH levels, trough LH levels, and LH pulse frequency compared to those in saline-treated control rats. The amplitude of LH pulses was not significantly affected by any dose of LHRH. In contrast to LH, multiple icv injections of LHRH failed to alter pulsatile FSH release. Pituitary LH and FSH responses to iv LHRH injection were not suppressed by icv LHRH. In a second experiment, hourly icv injections of 1 ng LHRH into proestrous rats markedly suppressed preovulatory LH release only during the middle to latter phases of the surge. In a final study using an in vitro superfusion system, addition of a LHRH agonist to the superfusion medium at a concentration that does not cross-react in the LHRH RIA suppressed basal and K+-stimulated LHRH release from medial basal hypothalamic fragments, but not from median eminence explants. These results support the existence and operation of an autoregulatory mechanism for LHRH in the central nervous system which may participate in the control of episodic LHRH release in ovariectomized rats and preovulatory LHRH release in proestrous rats. Seemingly, ultrashort-loop negative feedback regulation of LHRH requires the presence of structures other than nerve terminals in the MBH (i.e. cell bodies).