Syed M. Amir

Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole

Abstract In view of the controversy regarding the role of human chorionic gonadotropin as the stimulator of thyroid function in patients with trophoblastic tumors, especially hydatidiform mole, we conducted studies to explore whether a correlation between serum human chorionic gonadotropin levels and thyroid function was demonstrable in such patients. Among 47 patients studied, only one was clinically hyperthyroid, although 10 had serum total thyroxine values exceeding those found in normal pregnancy (8 to 17 μg/dl). Among 34 patients in whom free thyroxine indices could be calculated, 18 had elevated values for the free thyroxine index (>10.6), and nine had elevated values for both total thyroxine and free thyroxine index. Serum total 3,5,3′-triiodothyronine concentrations were also measured in 17 patients, and only one of them had a value (400 ng/dl) above the normal limit for pregnancy (>350 ng/dl). Among the 13 patients for whom free 3,5,3′-triiodothyronine indices were calculated, three had values above the normal range (>215). A weakly positive correlation (r = 0.35, p 0.05, n = 34). Also there was no correlation between serum human chorionic gonadotropin levels and either serum total 3,5,3′-triiodothyronine concentrations (r = 0.32, p > 0.1, n = 17) or free 3,5,3′-triiodothyronine index values (r = 0.27, p > 0.1, n = 13). χ2 Analysis revealed no significant relationship between elevations of serum human chorionic gonadotropin concentration and abnormally high values of the free thyroxine index. These studies do not support the premise that human chorionic gonadotropin per se is the thyroid stimulator of molar pregnancy and suggest that a substance or substances, distinct from human chorionic gonadotropin and elaborated by the gestational trophoblastic tissue, are responsible for thyrotoxicosis observed in patients with trophoblastic tumors.

Divergent responses by human and mouse thyroids to human chorionic gonadotropin in vitro

hCG is a known stimulator of mouse thyroid in vivo. Studies were therefore performed to ascertain whether the thyroid-stimulating activity of hCG in the mouse could also be demonstrated by the in vitro techniques that had failed to show any activity of hCG in the human thyroid. When labeled with 125I and incubated at 22 degrees C in 20 mM Tris-0.5% bovine serum albumin (Tris-BSA), pH 7.45, with increasing concentrations (70-300 micrograms protein/ml) of a mouse thyroid fraction, a purified hCG preparation [( 125I]hCG) showed 5-12% specific binding. In contrast, its binding to a human thyroid particulate fraction, over the same range of protein concentrations, did not exceed 1%. When similar studies were performed at 37 degrees C in 10 mM Tris-50 mM NaCl-0.5% BSA, pH 7.45, [125I]hCG showed no detectable binding either to the human or the mouse thyroid fractions. At concentrations ranging from 1 to 20 mIU/ml (0.9-18 X 10(-9) M), bTSH stimulated cAMP release from human thyroid slices into the medium in a dose-dependent manner. In contrast, hCG concentrations from 10(3) to 10(4) IU/ml (2-20 X 10(-6) M) were without effect on cAMP release. bTSH, at concentrations of 4.5 and 9.0 mIU/ml (4 and 8 X 10(-9)M), stimulated cAMP release from the mouse thyroid, producing in the medium approximately 11- and 28-fold increases in cAMP concentration. hCG also stimulated cAMP release from the mouse thyroid, the increases being approximately 2.3- and 1.8-fold, in the presence of 2270 and 4540 IU/ml (4.5 and 9.0 X 10(-6) M), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions of bovine thyrotropin and human chorionic gonadotropin with adenylate cyclase in bovine thyroid membranes.

Previous studies have shown that crude preparations of human chorionic gonadotropin bind to bovine thyroid membranes, displace 125I-labeled bovine thyrotropin therefrom, and are weak agonists therein with respect to the activation of adenylate cyclase. The present studies reveal that concentrations of chorionic gonadotropin sufficient to elicit a maximal agonistic response of adenylate cyclase are strongly antagonistic to the stimulatory action of bovine thyrotropin in the thyroid membrane system. This effect is reminiscent of the inhibitory effects of crude human chorionic gonadotropin on other extragonadal tissues in vitro, and, like them, appears to be mediated by some factor(s) other than human chorionic gonadotropin itself, since highly purified human chorionic gonadotropin was without effect.

The Charge Characterization of Native and Deglycosylated Thyrotropin

Chromatofocusing was used to characterize the charge microheterogeneity of crude pituitary, highly purified native bovine (b) and deglycosylated (dg) thyrotropin (TSH) preparations. Greater than 90% of crude pituitary TSH and native bTSH-I-1 bound to concanavalin-A (conA) columns while dgbTSH was excluded from the column. Extracts of ovine (o) pituitaries contained at least nine species (isohormones) of immunoreactive TSH when chromatofocused on pH 7.5-4 gradients. Highly purified native bTSH-I-1 displayed a similar elution profile. In contrast, dgbTSH eluted as a single homogeneous species with an apparent pI greater than 7.5. When subjected to chromatofocusing on a pH 10.5-7 gradient, 68% of crude pituitary oTSH and 96% of native bTSH-I-1 was bound to the column but could be eluted with NaCl indicating acidic species, while at least three peaks of dgbTSH could be resolved having apparent pIs of 9.12, 9.03 and 8.98. These data suggest that although removal of the carbohydrate moieties markedly alters the isohormone pattern of TSH, chemical deglycosylation does not completely eliminate the charge microheterogeneity of bTSH.