Thyroid-Stimulating Activity in Sera of Normal Pregnant Women

Abstract

To evaluate the effect of a thyroid stimulator on thyroid function in the sera of normal pregnant women, we measured thyroid-stimulating activity (TSA) using a highly sensitive bioassay based on cAMP accumulation in cultured rat FRTL-5 thyroid cells. Serum was pretreated with 10% polyethylene glycol (PEG), and the supernatant (PEG-pretreated serum) was then used in the following studies. FRTL-5 cells were preincubated in 5H medium and incubated for 2 h with PEG pretreated serum, and cAMP was measured. All 11 patients with untreated hyperthyroid Graves' disease with strongly positive thyroid-stimulating antibody activity had normal TSA, because only 5.6% of their immunoglobulin G was recovered in the PEG-pretreated serum. In 32 normal pregnant women, 29 (91%) had positive TSA. Their TSA showed statistically significant positive correlations with serum hCG and free T4 levels, and a negative correlation with serum TSH levels. Moreover, when hCG was absorbed from sera by incubation with the solid phase anti-HCG monoclonal antibody, a significant positive correlation was observed between the rate of decrease in hCG and that in TSA. In conclusion, 1) TSA exists in the sera of normal pregnant women, which reflects hCG itself; and 2) thyroid glands of normal pregnant women may be stimulated by TSA to induce a slight suppression of TSH but not sufficient to induce overt hyperthyroidism.

Maternal thyroid function in multifetal pregnancies before and after fetal reduction

“…The origin of the increased maternal thyroid function is almost certainly stimulation of the TSH receptor by human chorionic gonadotrophin (hCG) (Guillame et al 1985, Yoshikawa et al 1989, Glinoer et al 1990, Ballabio et al 1991. As the fetal thyroid is active only after 14 weeks gestation,it is suggested that the increased maternal thyroid activity ensures that normal neuronal development occurs in the fetus (Shepard 1975).…”

Human Chorionic Gonadotropin Promotes Thyroid Growth via Thyrotropin Receptors in FRTL-5 Cells.

“…In all 9 normal pregnant women in the first trimester, TGA was within the normal range However, in two patients with hydatidiform mole, TGA was positive. We previously found thyroid stimulating activity determined by cAMP accumulation in the sera of almost all normal pregnant women (Yoshikawa et al, 1989a). The reason why TGA could be detected only in some patients with hydatidiform mole may be Lineweaver-Burk plots of dose response curves of TSH-(the upper two panels) and hCG-(the lower two panels) induced [3H] Tdr incorporation in the presence of normal IgG or blocking IgGs from patients with primary hypothyroidism (patients 5 and 10 listed in Table 1: patient 5 is shown in the left two panels and patients 10 in the right).…”

“…The cloned rat thyroid cell line ERTL-5, established from cells of rat thyroid adenoma by Ambesi-Impiombato et al (1980) was cultured as previously described (Yoshikawa et al, 1989b Serum pretreatment with PEG Serum was pretreated with PEG by the method previously described (Yoshikawa et al, 1989a). Briefly, serum was dialyzed against the Hanks' Balanced Salt Solution, incubated for 1h at 4 C with 10% PEG, centrifuged at 10,000 pretreated serum) was used for the TGA assay.…”

“…We recently reported that thyroid stimulating activity (TSA) exists in the sera of normal pregnant women which reflects hCG itself (Yoshikawa et al, 1989a). Many investigators have reported that human chorionic gonadotropin (hCG) has intrinsic thyrotropic activity in regard to activating adenylate cyclase (Silverberg et al, 1978;Carayon et al, 1980;Davies and Platzer, 1986;Hershman et al, 1988;Yoshikawa et al, 1989a), and to promoting thyroid growth (Davies and Platzer, 1986;Hershman et al, 1988).…”

“…Many investigators have reported that human chorionic gonadotropin (hCG) has intrinsic thyrotropic activity in regard to activating adenylate cyclase (Silverberg et al, 1978;Carayon et al, 1980;Davies and Platzer, 1986;Hershman et al, 1988;Yoshikawa et al, 1989a), and to promoting thyroid growth (Davies and Platzer, 1986;Hershman et al, 1988). Furthermore, it has been reported that some patients with trophoblastic diseases had goiters (Smiley and Clements, 1940;Myers, 1961;Cohen and Utiger, 1970;Morley et al, 1976;Cave and Dunn, 1976;Nisula and Taliadouros, 1980), suggesting the existence of thyroid growth-promoting activity (TGA) in the sera of these patients, although, to our knowledge, no investigator has succeeded in detecting TGA in the patients' sera.…”