Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

Abstract

A search for inhibitors of urokinase-type plasminogen activator (uPA) in the male and female murine genital tracts revealed high levels of a uPA ligand in the seminal vesicle. This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes. A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs. PN-I is synthesized in the epithelium of the seminal vesicle, as determined by in situ hybridization, and is secreted in the lumen of the gland. PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control.

The kidney is a major site of alpha(2)-antiplasmin production.

“…Of interest, mouse liver ␣ 2 -AP mRNA accumulation was not influenced by androgens, demonstrating a tissue-specific endocrine regulation of ␣ 2 -AP production. Another serpin, proteasenexin I (PN-I), is also under androgen control in a subset of the tissues in which it is expressed (23). Further studies are required to determine if the accumulation of ␣ 2 -AP mRNA in the human kidney is also sexually dimorphic.…”

Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.

“…Lungs from saline-washed mice were dissected, frozen immediately in liquid nitrogen, and stored at Ϫ 80 Њ C. After homogenization in guanidinium/thiocyanate, total RNA was isolated by cesium chloride centrifugation as described previously (13). uPA, tPA, PAI-1, PAI-2, ␣ 2-antiplasmin ( ␣ 2-AP), and protease-nexin I (PN-I) probes were prepared as described (14)(15)(16)(17)(18) and transcribed in vitro using ␣ 32 P-labeled UTP (specific activity 400 Ci/mmol; Amersham International, Buckinghamshire, United Kingdom). RNase protection assays were performed as described (19).…”

Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1

“…Protease nexin-1 (PN-1), a serine protease inhibitor belonging to the serpin superfamily, can modulate the proteolytic activity of thrombin, plasminogen activators, trypsin, and plasmin (18)(19)(20)(21). Mouse PN-1 is expressed in a wide variety of tissues (22) but in the adult the highest levels are found to be under androgen control in the seminal vesicle (23). By inhibiting uPA and possibly other serine proteases, PN-1 could regulate the level of proteolytic activity in the seminal fluid.…”