Graded hyperprolactinemia first suppresses LH pulse frequency and then pulse amplitude in castrated male rats

We recently demonstrated that the ability of administered ovine prolactin (oPRL) to suppress postcastration LH secretion exhibited a clear dose 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. Adult 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 micrograms/injection) suppressed mean LH titers in a dose-dependent manner at 48 h postcastration. The mean maximal LH increments (delta LH) to two LHRH challenges at two doses (5 and 25 ng LHRH/100 g body weight) were unaffected by oPRL administration. The 600 micrograms oPRL dose significantly suppressed 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, respectively). The two higher oPRL doses suppressed both LH pulse frequency and 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 significant proportion of the LHRH neurons projecting to the median eminence, the present data suggest that the neurons first affected by elevated PRL levels are the ones responsible for this frequency of this coordinated firing.(ABSTRACT TRUNCATED AT 250 WORDS)