Orchidectomy Induces Temporal and Regional Changes in the Processing of the Luteinizing Hormone-Releasing Hormone Prohormone in the Rat Brain

Abstract

The structures of the complementary DNA (cDNA) that encode the rat and human hypothalamic LHRH prohormones were recently determined and the corresponding amino acid sequences deduced. In addition to the LHRH decapeptide, the prohormone contains a 56-amino acid peptide sequence which has been designated gonadotropin-releasing hormone associated peptide (GAP). In the present study we examined the effect of orchidectomy on LHRH prohormone processing in three brain regions known to contain the various elements of the LHRH neuronal system; the preoptic-anterior hypothalamic area, the hypothalamus (HYP), and the median eminence. Both LHRH-like and GAP-like immunoreactivities (LHRH-LI and GAP-LI) were quantitated in these regions in intact male rats and male rats orchidectomized for 1, 2, 3, 5, 7, 14, or 40 days. In addition, the LHRH and GAP immunoreactivities were localized and the effects of orchidectomy examined using immunocytochemical techniques. One day after orchidectomy, a small decrease in GAP-LI and an increase in LHRH-LI were evident in extracts of the preopticanterior hypothalamic area which resulted in a significant decrease in the GAP/LHRH molar ratio. A similar selective decrease in GAP-LI and in the GAP/LHRH molar ratio was also observed in extracts of the HYP, but not until 2 days after orchidectomy. The GAP/LHRH ratio in both regions gradually returned to that of the intact controls. In both the HYP and median eminence, GAP-LI and LHRH-LI gradually declined in parallel through 14 days after orchidectomy. The gradual loss of immunoreactivity in these regions was evident by both RIA quantification and immunocytochemistry. These observations suggest that 1) production and processing of both LHRH and its prohormone are affected by testicular factors, 2) that divergent enzyme and/or transport systems, regulating LHRH and GAP processing, may exist at the level of the perikarya, and 3) long term orchidectomy results in decreased biosynthesis of the prohormone and/or in parallel increases in LHRH and GAP degradation or transport.