Rat Testicular Germ Cells and Sertoli Cells Release Different Types of Bioactive Transforming Growth Factor-B in vitro

B.L. Haagmans, J.W. Hoogerbrugge, A.P.N. Themmen, K.J. Teerds

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17 Citations (Scopus)


Several in vivo studies have reported the presence of immunoreactive transforming growth factor-ß's (TGF-ß's) in testicular cells at defined stages of their differentiation. The most pronounced changes in TGF-ß1 and TGF-ß2 immunoreactivity occurred during spermatogenesis. In the present study we have investigated whether germ cells and Sertoli cells are able to secrete bioactive TGF-ß's in vitro, using the CCl64 mink lung epithelial cell line as bioassay for the measurement of TGF-ß. In cellular lysates, TGF-ß bioactivity was only observed following heat-treatment, indicating that within these cells TGF-ß is present in a latent form. To our surprise, active TGF-ß could be detected in the culture supernatant of germ cells and Sertoli cells without prior heat-treatment. This suggests that these cells not only produce and release TGF-ß in a latent form, but that they also release a factor which can convert latent TGF-ß into its active form. Following heat-activation of these culture supernatant's, total TGF-ß bioactivity increased 6- to 9-fold. Spermatocytes are the cell type that releases most bioactive TGF-ß during a 24 h culture period, although round and elongated spermatids and Sertoli cells also secrete significant amounts of TGF-ß. The biological activity of TGF-ß could be inhibited by neutralizing antibodies against TGF-ß1 (spermatocytes and round spermatids) and TGF-ß2 (round and elongating spermatids). TGF-ß activity in the Sertoli cell culture supernatant was inhibited slightly by either the TGF-ß1 and TGF-ß2 neutralizing antibody. These in vitro data suggest that germ cells and Sertoli cells release latent TGF-ß's. Following secretion, the TGF-ß's are converted to a biological active form that can interact with specific TGF-ß receptors. These results strengthen the hypothesis that TGF-ß's may play a physiological role in germ cell proliferation/differentiation and Sertoli cell funct
Original languageEnglish
Pages (from-to)1-6
JournalReproductive Biology and Endocrinology
Issue number3
Publication statusPublished - 2003


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