Ultrashort feedback control of luteinizing hormone-releasing hormone secretion in vitro

The present experiments were performed to clarify whether LHRH might inhibit its own secretion via an ultrashort feedback mechanism acting directly on the hypothalamus. Using an in vitro system, mediobasal hypothalami (MBHs) of adult male rats were perifused in either the presence or absence of a LHRH agonistic analog [D-Ser(TBU)6,Des-Gly10] LHRH ethylamide shown not to cross-react in the LHRH RIA. In the first series of experiments, six MBHs per chamber were initially perifused with control medium and submitted to two K+ stimulations (110 mM) for 5 min every 30 min; the control medium was then replaced by medium containing the LHRH analog (5 microM), and three additional K+ pulses were applied. In the second series of experiments, a single MBH per chamber was exposed for the duration of the experiments to either control medium or medium containing the LHRH analog (5 microM). In both cases, pulses of K+ were applied to the tissue. The amounts of endogenous LHRH released both under basal conditions and after K+ stimulation were measured in the effluent (1 ml every 5 min) with a specific RIA. The results show that the LHRH analog inhibits basal secretion of endogenous LHRH from the MBH, and diminishes or abolishes the response to K+ stimulations. The specificity of the inhibitory effect exerted by the LHRH analog on LHRH secretion was shown by the inability of TRH to mimic the effect of the LHRH analog. The data are consistent with the hypothesis that LHRH, acting at a hypothalamic level, might participate in the control of its own release via an ultrashort feedback mechanism.