Human early placental trophoblasts produce an epidermal growth factor-like substance in synergy with thyroid hormone

Previous studies have shown that human trophoblast is the site of epidermal growth factor (EGF) localization, reception and action and that thyroid hormone exerts similar effects on trophoblasts endocrine function as observed with EGF. Thus, the present study was designed to examine local production of an EGF-like substance in synergy with thyroid hormone by early placenta. Explants of normal early (7-8 weeks) placentas were cultured in a serum-free condition in the presence or absence of L-triiodothyronine (T3), with or without cycloheximide for 4 days. The conditioned media were dialyzed, lyophilized, acidified and chromatographed over a Sephadex G-75 column equilibrated with 1 mol/l acetic acid. EGF was measured by a specific RIA for human EGF. Fractionation of the serum-free conditioned media resulted in the elution of immunoreactive EGF with an apparent molecular weight of 9,000 which is larger than [125I] human EGF. The addition of T3 (10(-8) mol/l) resulted in increased secretion of immunoreactive EGF by placental explants. By contrast, the addition of cycloheximide (5 x 10(-5) mol/l) dramatically reduced the secretion of immunoreactive EGF. The similarity of the immunoreactive EGF material to authentic human EGF was supported by parallel displacement in human EGF-RIA. These results suggest that human early placental trophoblast is capable of producing an EGF-like substance and that thyroid hormone enhances the local production of the EGF-like substance. This suggests that an autocrine/paracrine control system, wherein EGF serves as the signal in regulating placental growth and function in synergy with thyroid hormone, exists in human early placenta.