Effect of chronic DDC treatment on LHRH and substance P amidation processes in the rat

We examined the effects of chronic diethyldithiocarbamate (DDC) treatment on the concentrations of methionine-enkephalin, mature and unamidated forms (-Gly) of luteinizing hormone releasing hormone (LHRH) and substance P (SP) in various regions of the central nervous system (CNS). Chronic DDC treatment resulted in elevations of LHRH-Gly like immunoreactivity in the preoptic area (POA) and the medial basal hypothalamus (MBH), as well as elevations in SP-Gly like immunoreactivity in all areas of the CNS examined. Castration altered the ratios of SP-G-like/SP-like immunoreactivity in the pons, and LHRH-Gly like immunoreactivity in the MBH. Met-enkephalin concentrations were significantly elevated in the pons and medulla of intact DDC-treated animals, and in the POA of both intact- and castrated DDC-treated animals. Results demonstrate that it is possible to detect basal levels of unamidated LHRH and SP in many areas of the CNS, with ratios of unamidated/amidated peptides representing a unique and sensitive method for determining altered posttranslational processing of these transmitters, especially under altered endocrine states such as castration. Pharmacological blockade of terminal enzymatic processing of these peptides may be useful in studying upstream regulatory events in peptidergic neurons.