Reinke Crystals are Immunoreactive for Purine-Synthesising 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.

We sought to explore the protein composition of Reinke crystals.

Double labelling immunofluorescence for the purine nucleotide-synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and phosphoribosyl pyrophosphate synthetase (PRPS) and confocal microscopic imaging were performed on samples of human Leydig cell tumours and adjacent non-neoplastic testis.

We demonstrate that Reinke crystals are intensely immunoreactive for IMPDH and 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 potentially link Reinke crystal formation to purine nucleotide metabolism in Leydig cells.

If confirmed in future studies, this finding may have important implications for understanding metabolic contributions to male reproductive disorders.