Maturation of pituitary-thyroid function in the anencephalic fetus

The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric assays for TSH and its subunit determination along with direct "two-step" assays for free thyroid hormone measurement, prompted us to study the maturation of hypothalamic-pituitary-thyroid axis in normal and anencephalic human fetuses from 17 to 26 weeks of gestation. In addition, TSH bioactivity was measured as cAMP accumulation in CHO cells transfected with recombinant human TSH receptor and TSH carbohydrate structure was studied by lectin chromatography. In both normal and anencephalic fetuses, circulating TSH and FT4 levels significantly increased from 17 to 26 weeks of gestation. Circulating FT3 concentrations were very low (0.5-3.1 pmol/l), while alpha-SU levels were very high (20-417 mg/l). Both FT3 and alpha-SU levels did not change from 17 to 26 weeks of gestation and, again, no differences between normal and anencephalic fetuses were recorded. Circulating TSH from both normal and anencephalic fetuses showed an enhanced bioactivity and was more retained on the lectin column than adult TSH, thus indicating that molecules with different carbohydrate structure are circulating during fetal development. In conclusion, the present data demonstrate that the absence of the hypothalamus does not compromise the maturation of pituitary-thyroid function and that the mechanisms underlying the secretion of TSH molecules with elevated bioactivity and different structure of glycosylated chains are not dependent on hypothalamic neuroendocrine control.