Androgen responsiveness and intrarenal localization of transcripts coding for the enzymes of polyamine metabolism in the mouse

Polyamines, spermidine (SPD), and spermine (SPM) are intracellular polycati ons required for cell growth and differentiation. Their biosynthetic precur sor, the diamine putrescine (PUT), is produced by regulatory ornithine deca rboxylase (ODC). Spermidine/spermine N-1-acetyltransferase (SSAT) is the OD C counterpart in the degradation pathway which retroconverts SPM and SPD in to PUT. Castration of male mice for 7 days resulted in a 40% decrease of th e renal levels of both SSAT and ODC transcripts. Administration of 5-alpha- dihydrotestosterone (DHT) to castrated mice for the last 3 days before sacr ifice caused the levels of ODC and SSAT mRNAs to increase by 250% and 180%, respectively. Thus activation of the retroconversion pathway of polyamine metabolism appears to contribute towards the increase in PUT production kno wn to be caused by androgens in the mouse kidney. In situ hybridization his tochemistry experiments showed that the SSAT transcript is expressed only b y the epithelial cells of the straight and convoluted distal tubules of the nephron, while the expression of the ODC transcript is confined to the epi thelium of the convoluted and straight portion of the proximal tubules. The separation of the biosynthetic from the degradation pathway along the neph ron suggests that PUT is mostly produced in the distal tubule, where it may play a physiological role, independent of androgen action, in protecting t ubular cells from the very low osmolarity to which they are exposed in this nephron segment.