GRADED HYPERPROLACTINEMIA FIRST SUPPRESSES LH PULSE FREQUENCY AND THEN PULSE AMPLITUDE IN CASTRATED MALE-RATS

We recently demonstrated that the ability of administered ovine prolac tin (oPRL) to suppress postcastration LH secretion exhibited a clear d ose dependency. In the present study, we determined whether this dose- related suppression of mean LH levels resulted from differential, dose -related effects of oPRL on LH pulse amplitude and pulse frequency. Ad ult male rats were orchiectomized and adrenalectomized, implanted with an atrial cannula and a 50% corticosterone pellet, and injected every 12 h with oPRL or its polyvinylpyrrolidone (PVP) vehicle beginning at time 0. Increasing doses of oPRL (600, 2,400 and 9,600 mu g/injection ) suppressed mean LH titers in a dose-dependent manner at 48 h postcas tration. The mean maximal LH increments (Delta LH) to two LHRH challen ges at two doses (5 and 25 ng LHRH/100 g body weight) were unaffected by oPRL, administration. The 600 mu g oPRL dose significantly suppress ed mean LH values by markedly increasing the inter-peak interval(42.6 +/- 6.7 min) compared with controls (26.6 +/- 0.2 min) since the pulse amplitude was unaffected (2.8 +/- 0.4 vs. 2.6 +/- 0.4 ng/ml, respecti vely). The two higher oPRL doses suppressed both LH pulse frequency an d pulse amplitude. Hence, elevated PRL levels first suppress LH pulse frequency and then, at higher concentrations, pulse amplitude as well. Presuming that LHRH pulses result from ensemble firing of all or a si gnificant proportion of the LHRH neurons projecting to the median emin ence, the present data suggest that the neurons first affected by elev ated PRL levels are the ones responsible for the frequency of this coo rdinated firing. Possible candidates for this neuronal mechanism would be the LHRH-LHRH collateral connections and/or other hypothalamic int erneurons.