PREFERENTIAL DISTRIBUTION OF C-TERMINAL FRAGMENTS OF [HYDROXYPROLINE(9)]LHRH IN THE RAT HIPPOCAMPUS AND OLFACTORY-BULB

Several molecular forms related to the decapeptide LHRH were character ized and quantified in various brain structures of intact and castrate d male and female rats. Distinct moieties were separated by high perfo rmance liquid chromatography (HPLC) and radioimmunoassayed against ant i-LHRH antibodies of different specificities. The hypothalamus contain ed the highest concentration of LHRH-like material detected by the ant isera. The predominant (89%) molecular form recovered from that struct ure was LHRH itself; 9% of the material corresponded to [hydroxyprolin e9]LHRH ([Hyp9]LHRH), an endogenous posttranslational product of the L HRH precursor, and the residual immunoreactivity was accounted for by C-terminal fragments of both decapeptides, as assessed after labelling HPLC columns with appropriate synthetic or endogenous hypothalamic pe ptides. The proportions were the same in both sexes and were not affec ted by castration, in spite of a lesser overall LHRH activity in femal es and in castrates. LHRH and [Hyp9]LHRH were also detected in the olf actory bulb and the hippocampus. In these structures however, most (97 %) LHRH-related molecules corresponded to C-fragments derived from [Hy p9]LHRH, whereas only very few fragments derived from the nonhydroxyla ted decapeptide were found. Sex or castration affected neither total n or relative concentrations of LHRH-derived molecules in the olfactory bulb and the hippocampus. Taken altogether, these observations are sug gestive of a different LHRH metabolic regulation in neurons projecting to either the median eminence or extrahypothalamic areas. In the latt er case, larger amounts of the LHRH precursor appear processed to [Hyp 9]LHRH. Recovery of relatively high concentrations of [Hyp9]LHRH C-fra gments in the olfactory bulb and the hippocampus reflects the higher r esistance of the Hyp9-Gly10-NH2 than the Pro9-Gly10-NH2 peptidic bond to hydrolysis by the postproline cleaving enzyme. In view of reports t hat intracerebral administration of C-terminal fragments of LHRH are a ble to trigger sex behavior, our finding that extrahypothalamic struct ures contain relatively high concentrations of the [Hyp9]LHRH-derived, more stable C-fragments suggests that these catabolites may have a ro le in the regulation of sex behavior.