Expression of Matrix Metalloproteases (MMP-2, MT1-MMP) and Their Tissue Inhibitor (TIMP-2) by Rat Sertoli Cells in Culture: Implications for Spermatogenesis

Abstract

During testicular development and maturation, extracellular matrix (ECM) remodelling is a fundamental process which requires the presence of several proteases and protease inhibitors. Among the proteases, a pivotal role has been proposed for matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs). Here we report an analysis of MMP-2, MT1-MMP and TIMP-2 expression by rat Sertoli cells in culture using RT-PCR and zymographic techniques. Stimulating Sertoli cells with follicle-stimulating hormone (FSH) in vitro induced evident changes in the level of their mRNA in a time-dependent manner. In the case of TIMP-2 and MT1-MMP, the respective transcripts were augmented up to three-fold after 24 h of treatment, and MMP-2 transcripts increased by four times in the same period. MMP-2 activity determined by gelatin zymography showed an increase in enzyme secretion after FSH stimulation. The results of this study suggest that: (i) at the surface of Sertoli cells pro-MMP-2 activation mediated by MT1-MMP may occur, involving TIMP-2 as a receptor; and (ii) the expression of these molecules is not constitutive in this cell type, but may be modulated by FSH and is therefore implicated in spermatogenesis.

TNF Alpha-Mediated Disruption of Spermatogenesis in Response to Sertoli Cell Injury in Rodents Is Partially Regulated by MMP21

“…Only TIMP2 and TIMP4 were detectable in conditioned media of primary Sertoli cell-germ cell cocultures (data not shown), further narrowing the likely participation of TIMPs in the seminiferous epithelium to these two TIMP family members. Previous studies [19,31,32] indicate that both TIMP1 and TIMP2 are expressed by Sertoli cells, that TIMP3 is found within interstitial cells such as Leydig cells, and that TIMP4 is present in both interstitial cells and Sertoli cells. Our results suggest that TIMP2 is predominantly expressed in Sertoli cells and show that, after MEHP exposure, its protein levels are specifically reduced in vitro (Fig.…”

“…The objectives of this study were to determine the functional significance of TNFA in modulating the sensitivity of germ cells to undergo apoptosis and to evaluate the mechanism of TNFA processing in the seminiferous epithelium. Metalloproteinases (MPs) are essential for processing the TNFA precursor [14][15][16][17], and several MPs in the testis have been described [18][19][20][21]. Most MPs are extracellular enzymes that are released as an inactive latent form and are further activated through proteolytic processing.…”

Global analysis of differentially expressed genes in androgen-independent prostate cancer

“…54 Addition of follicle-stimulating hormone to Sertoli cells increased the MMP-14 mRNA level, implicating a role in spermatogenesis. 55 Genes of C3, hormone-sensitive lipase and peroxisome proliferative-activated receptor-gamma may exert a modifying effect on lipid and glucose metabolism in familial combined hyperlipidemia. 56 CASP6 is sufficient for full activation of melanin-concentrating hormone receptor 2.…”

The role of microenvironment in testicular germ cell tumors

“…63 RT-PCR has demonstrated the overexpression of the gelatinases, MMP-2 and MMP-9, in ES cell-derived experimental teratocarcinomas, whereas expression is not detected in normal testis samples. 64 MMP-2 and MT1-MMP expression has been also reported in Sertoli cells and, surprisingly, the expression of these proteases is upregulated in vitro by follicle-stimulating hormone (FSH), 65 which is especially active during puberty and, thus, could be involved in TGCT development.…”