Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy.

Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10(-8) mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17 beta as well as hCG alpha, hCG beta, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17 beta secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10(-8) mol/l) enhances 3 beta-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10(-8) mol/l) on the trophoblast endocrine function were also found with the use of T4 (10(-7) mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.