Onset of Function in the Human Fetal Thyroid: Biochemical and Radioautographic Studies from Organ Culture¹

Abstract

Nineteen human fetal thyroids obtained in fresh condition were studied by the use of short-term organ culture. The incorporation of 125I added to the culture medium was investigated by means of biochemical and histologic techniques both in the gland and in a suitable control tissue. The crown-rump length of the fetuses ranged from 22 to 142 mm, which is equivalent to an estimated gestational period of 45–112 days. In the 7 fetuses of less than 68 mm no organic iodine, central colloid cavity or tissuebound 125I were found. At the 68 mm stage (74 gestational days) and at all later stages a full spectrum of organically bound, iodinated products was found (MIT, DIT, T4, and occasionally T3) and the tissue evidenced 125I binding in radioautographs. Sequential steps of biochemical maturation as reported in experimental animals were not identified in these tests. The control tissue contained only radioiodide. Sections of epon-embedded thyroid tissue, 1 μ in thickness, permitted identification of intracellular canaliculi previously seen only with the electron microscope. These organelles are believed to be the precursors of the central colloid cavity which is formed by fusion of these structures into a central luminal space. These early canaliculi were not associated with evidence of isotope binding but in the later stages the cavities in the process of union did localize 125I. Thyroids of 20-day rat fetuses in a similar organ culture system progressively accumulated radioiodine, and a gradual reduction of the MIT to DIT ratio occurred over an 18-hr period. Boiling the glands prevented any metabolism of iodide, and propylthiouracil inhibited organic binding of the isotope. Cyanide did not decrease the incorporation of iodide at 10−3m concentration. Puromycin, in a concentration as low as 10−5m, caused over 50% inhibition of incorporation. The metabolism of 125I by differentiated human fetal thyroid was decreased significantly by freezing or by a 2-hr delay in transfer of the gland from the fetus to the incubating medium.