Modulation of prohormone convertase 2 in spinal cord during gestation and hormone-simulated pregnancy

Gestation as well as its hormonal simulation (HSP) is characterized by an e nhanced spinal dynorphin/kappa-opioid antinociception. This antinociception is accompanied by decreased content of dynorphin precursor intermediates a nd increased content of mature dynorphin peptides (1-17 and 1-8) in the lum bar spinal region. This suggests that augmented processing of spinal dynorp hin precursor intermediates is an adaptive mechanism used by dynorphin neur ons to meet increased synthetic demands necessitated by increased dynorphin neurotransmission. Prohormone convertase (PC) 1 and 2 represent major secr etory granule proteolytic processing activities capable of converting neuro endocrine and neurotransmitter peptide (dynorphin) precursor intermediates to their mature, biologically active products. Accordingly, the current inv estigation was undertaken to assess their potential relevance to peptidergi c (dynorphin) neuronal functional plasticity in vivo. In order to evaluate a molecular biological parameter of PC2 synthesis, a solution hybridization assay was developed with which to quantify changes in the spinal lumbar co ntent of its mRNA, This study demonstrates that during gestation and HSP, l umbar PC2 protein content, but not that of PC1, is augmented. The increase in lumbar PC2 during HSP indicates that the pregnancy blood concentration p rofile of 17 beta-estradiol and progesterone is a predominant facet of the pregnant condition responsible for its modulation during this condition. In contrast to the elevated content of lumbar PC2 protein, levels of PC2 mRNA in the lumbar cord of pregnant or HSP rats were essentially unchanged. Thi s indicates that increased transcriptional activity is not, necessarily, a prerequisite for increased PC2 protein content to be manifest. These observ ations suggest positive modulation of PC2 to be a critical component of the mechanism(s) by which spinal dynorphin neurons adapt to the demand-induced increased production of mature dynorphin peptides.