The ontogeny of the thyrotropin-thyroid axis in early bovine embryos

T4 and T3 formation and their response to TSH, cAMP, and prostaglandin E2 (PGE2) stimulation were studied by RIA in cultured bovine fetal thyroids from 130 embryos of 1.2-25.0 cm crown-rump length (CRL). T4 and T3 were found in all of the freshly isolated glands studied, and their concentrations increased significantly (P less than 0.05) during a 24-h incubation of glands from fetuses with a CRL greater than 8.0 cm. The release of T4 (nanograms per mg tissue), but not of T3, increased consistently with CRL (r = 0.64; P less than 0.05). The addition of TSH (0.5 mU) to the culture medium induced a 2- to 3-fold increase in the secretion of T4, but not of T3, by glands of fetuses with a CRL of 3.0-25.0 cm (P less than 0.05). Dibutyryl cAMP (10(-4) M) and PGE2 (10(-4) M) had comparable effects. A combination of TSH and theophylline (1 mM) or of TSH and dibutyryl cAMP significantly enhanced the T4 released by cultured tissue into the medium (P less than 0.05) over that induced by either agonist, but the combined effect was not fully additive. The total PGE2 in the tissue and medium was not changed by the addition of 0.5 mU TSH, and indomethacin had no effect on TSH-induced T4 secretion. The data show that thyroids of fetuses that have reached a CRL of 3.0 cm have the enzymatic capacity to produce both T4 and T3, and T4 is the dominant product formed. While exogenous PGE2 at high concentrations stimulates fetal T4 secretion, it does not mediate the actions of TSH and cAMP on the fetal thyroid.