Dissertation

Thyrotropic activity of human chorionic gonadotropin: Biological, immunological and biochemical characterization

Ballabio, Maria

1992

Overview

Clinical evidence suggestive of a nonpituitary regulation of thyroid homeostasis in pregnancy seems to indicate that the placenta may function as an integrated control system, responding to feedback signals both from the fetal and the maternal compartments. This putative placental control system may be postulated to fulfill the critical role of ensuring an appropriate T4 environment for optimal fetal development through the synthesis and secretion of a placental thyroid stimulator. The aim of the study was to evaluate the thyroid stimulating activity (TSA) of human chorionic gonadotropin and to characterize different molecular forms of the hormone in relation to their ability to interact with thyroid tissue. The measurement of cAMP levels and I- uptake in FRTL-5 rat thyroid cells have been used as in vitro parameters indicating interactions with the TSH receptor and TSH-like biological activity of hCG and its isoforms. A dose-dependent response, paralleling that evoked by hTSH, was observed in a concentration range of 50-2,000 IU/ml of different preparations of hCG, 1 IU of hCG being equivalent to 0.13 μU of hTSH. TSA coeluted in a single peak with hCG immunoactivity at gel filtration and was not neutralized by monoclonal anti-hTSH antibodies indicating that it was not due to nonspecific protein or contamination by TSH. At chromatofocusing urinary hCG was resolved into six isoforms corresponding to pIs of 5.2, 4.9, 4.5, 4.0, 3.6 + some more acidic hCG-like material eluting in a final IM NaCl step. All the fractions were active in the TSH bioassay but the B/I ratio differed among hCG components ranging from 1.49±0.08 to 0.88±0.16, with the most basic component (pI 5.2) significantly more active and the most acidic component (1M NaC1) significantly less active than the unfractionated preparation. In parallel, hCG and TSH levels were measured in a longitudinal study of 32 normal pregnant women. In the 1st trimester samples, TSH levels were decreased and significantly correlated in a negative fashion with hCG levels (p<0.02). Seven 1st and 2nd trim, sera, out of ten cases studied, induced a significant increase in I- uptake, while no stimulation was obtained with post-partum sera. Although the response to 1st trim, samples was higher than to 2nd trim, sera, TSA was poorly correlated with hCG values when considering 1st and 2nd trimester individually. In these seven cases, a difference in the composition of circulating hCG was also observed between 1st and 2nd trim., with a shift towards more acidic forms at the earlier stage of gestation. This study has revealed a significant decrease of TSH levels in the 1st trimester of pregnancy when, however, the secretory activity of maternal thyroid gland is increased, supporting the view that the thyroid gland is not primarily TSH-driven in early pregnancy. hCG may represent the putative regulator of maternal thyroid function in pregnancy. In this context, hCG microheterogeneity may influence its thyrotropic activity, and the occurrence of different hCG isoforms may represent physiologically important steps in the control of the maternal thyroid.

• Publisher: ProQuest Dissertations & Theses
• Subject: Endocrinology / Medicine / Obstetrics
• ISBN: 9781369858662, 1369858663