Reinke crystals are immunoreactive for purine-synthesizing metabolic enzymes

Reinke crystals are a defining histological feature of human adult Leydig cells, the testosterone producing cells of the testis. These structures are present in the cytoplasm and the nucleus and display quantitative alterations in a variety of physiological and pathological contexts. The functional significance and protein composition of Reinke crystals have remained elusive for over a century. Here, we demonstrate that Reinke crystals are intensely immunoreactive for inosine monophosphate dehydrogenase (IMPDH), and phosphoribosyl pyrophosphate synthetase (PRPS), two key rate-limiting enzymes in the de novo synthesis of purine nucleotides. IMPDH and PRPS are two of several metabolic enzymes that are capable of forming mesoscale filamentous aggregates as a mechanism to regulate enzyme activity. IMPDH is also able to form crystals in cellulo. Our observations link Reinke crystal formation to purine nucleotide metabolism in Leydig cells. We discuss how this novel finding may relate to the unique dependence of Leydig cells on guanyl-based purine nucleotides for testosterone synthesis. The results of this study may have important implications for understanding metabolic contributions to male reproductive disorders as well as offering a novel diagnostic and theranostic tool applicable to Leydig cell neoplasms.