Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts

• Published in: The journal of clinical endocrinology and metabolism Vol. 74; no. 1; p. 211
• Main Authors: Matsuzaki, N, Li, Y, Masuhiro, K, Jo, T, Shimoya, K, Taniguchi, T, Saji, F, Tanizawa, O
• Format: Journal Article
• Language: English
• Published: United States 01.01.1992
• Subjects: Chorionic Gonadotropin - metabolism; Cytokines - pharmacology; Gonadotropin-Releasing Hormone - pharmacology; Humans; Interleukin-1 - antagonists & inhibitors; Interleukin-6 - metabolism; Recombinant Proteins; Reference Values; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - pharmacology; Trophoblasts - chemistry; Trophoblasts - metabolism
• ISSN: 0021-972X
• DOI: 10.1210/jc.74.1.211

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.