Molecular Endocrinology, Vol 5, 1789-1798, Copyright © 1991 by Endocrine Society

ARTICLES

Cyclic protein-2, a secretory product of rat Sertoli cells, is the proenzyme form of cathepsin L

M Erickson-Lawrence, SD Zabludoff and WW Wright
Department of Population Dynamics, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205.

Previous studies demonstrated that secretion of Cyclic Protein-2 (CP-2) by mature rat Sertoli cells increased 30-fold from stage II to stages VI-VII of the cycle of the seminiferous epithelium and suggested that this protein was concentrated around compacted spermatids. Analysis of other organs revealed that CP-2 was also detectable in the epithelium of the proximal kidney tubule and in neurons originating from the supraoptic and paraventricular nuclei of the hypothalamus. We now have isolated a partial 1.8-kilobase (kb) cDNA for CP-2 mRNA, and sequence analysis revealed that CP-2 was the proenzyme form of the cysteine protease cathepsin L; this was corroborated by immunoprecipitation of CP-2 by anticathepsin L immunoglobulin G and by enzymatic analysis of purified CP-2. Northern analysis of testis mRNA revealed major (1.7 kb) and minor (2.2 kb) transcripts which differed in the length of their 3'- untranslated sequences. Low levels of CP-2/cathepsin L transcripts were detected in many organs, while high levels were only detected in testis, kidney, and liver. In seminiferous tubules, CP-2/cathepsin L mRNA was undetectable at stage II, increased to maximal levels at stages VI and VIIa,b, and was again undetectable at stage XII. At stages VI-VII, CP-2/cathepsin L mRNA was present in Sertoli but not germ cells. Taken together, these data suggest that CP-2/cathepsin L gene expression is regulated in a cell-specific manner and that in Sertoli cells this expression is influenced by germ cells at specific steps of development. We propose that at stages V-VII, secreted CP- 2/cathepsin L degrades adhesion molecules which bind compacted spermatids to Sertoli cells, thereby facilitating movement of these spermatids toward the lumen of the tubule.

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