Orchidectomy Induces Temporal and Regional Changes in the Synthesis and Processing of the LHRH Prohormone in the Rat Brain

Abstract

Recently, the sequence of the cDNA which encodes the LHRH-prohormone was elucidated from human placenta and human and rat hypothalamus and the corresponding amino acid sequence deduced (Seeburg et al., 1984 and Adelman et al., 1986). In addition to LHRH, the prohormone contains a 56 amino acid sequence, designated gonadotropin-releasing hormone associated peptide (GAP), which is attached to the C-terminus of the LHRH decapep-tide. Although not yet confirmed, the human GAP sequence has been reported to possess both gonadotropin-releasing and prolactin inhibiting activity (Nikolics et al., 1985). Additionally, a 13-amino acid fragment of the human GAP sequence (proLHRH 14–26) has been reported to stimulate gonadotropin release (Millar et al., 1986). Regardless of whether the non-LHRH portion of the LHRH prohormone contains biological activity, this sequence can serve as a valuable marker for studies of LHRH prohormone synthesis, processing and degradation. In order to initiate these types of studies, we have generated specific antisera (MC-1, 2 and 3) against a fragment of the human GAP sequence (proLHRH 38–66) and developed a radioimmunoassay procedure for the quantitation of GAP (Culler and Negro-Vilar, 1986). The antisera are specific for midportion sequences of the GAP molecule and do not cross-react with any other known brain peptide.