Variations in levels of substance P-encoding beta-, gamma-preprotachykinin and substance P receptor NK-1 transcripts in the rat hypothalamus throughout the estrous cycle: a correlation between amounts of beta-preprotachykinin and NK-1 mRNA.

Using a sensitive RNase protection assay, the simultaneous quantification of hypothalamic beta-, gamma-preprotachykinin (PPT) and SP receptor NK-1 transcripts was performed throughout the estrous cycle. The amounts of these 3 transcripts were up-regulated during diestrus II-proestrus night (2-, 1.5- and 1.3-fold, respectively). These levels returned to low values during the proestrous day in the case of gamma-PPT mRNA and during the estrus-diestrus I night in the cases of beta-PPT and NK-1 mRNAs. These results implicate a differential regulation in amounts of the two alternatively spliced PPT transcripts. The 160 hypothalami of this study had been previously assayed for amounts of substance P (SP) and neurokinin A (NKA) peptides [P. Duval, V. Lenoir, S. Moussaoui, C. Garret and B. Kerdelhué, Substance P and neurokinin A variations throughout the rat estrous cycle; comparison with ovariectomized and male rats: I. Plasma, hypothalamus, anterior and posterior pituitary, J. Neurosci. Res., 45 (1996) 598-609]. Variations in mRNA and peptide levels were compared by statistical analysis. Surprisingly, variations in SP level paralleled those in beta-PPT mRNA level and variations in NKA level paralleled those of gamma-PPT mRNA level, although beta- and gamma-PPT transcripts encode both SP and NKA. Furthermore, the level of NK-1 mRNA was positively correlated with the level of beta-PPT mRNA (r = 0.90, P < 10(-58)) and with the level of SP peptide (r = 0.30, P < 10(-3)) but not with the level of NKA peptide. This analysis suggests that SP receptor NK-1 mRNA could be physiologically regulated by SP peptide in the rat hypothalamus.