Role of subunit sialic acid in hepatic binding, plasma survival rate, and in vivo thyrotropic activity of human chorionic gonadotropin.

Previous studies have shown that desialylation of human chorionic gonadotropin (hCG) results in a sharp enhancement of its affinity for thyroid thyroid-stimulating hormone (TSH) receptors, transforming it from a weak to a potent antagonist of adenylate cyclase activity in vitro. Because most of the information on the structure-function relation of hCG as a thyroid stimulator has been derived from in vitro experiments, the present studies were undertaken to assess the role of its sialic acid residues in the expression of its thyrotropic activity in vivo. hCG and its various desialylated forms, viz., intact-alpha-asialo-beta, asialo-alpha-intact-beta, and asialo-hCG (ashCG), were initially characterized in terms of their immunoreactivities and receptor-binding abilities as assessed in the rat testis assay. In neither assay did hCG or its variants exhibit a major discordance in activity. In the mouse bioassay, intact hCG (150 micrograms) proved to be a thyroid stimulator of considerable potency, exceeding the response induced by 0.2 mIU bovine TSH (bTSH), as measured by 125I release into the blood after 2- and 8-h intervals. Remarkably, both asialo-alpha-intact-beta and ashCG significantly stimulated the mouse thyroid in this assay, though to a lesser degree than hCG itself. However, in the same assay intact-alpha-asialo-beta was inactive. Studies of the survival of hCG and its variants in the circulation of the mouse, as assessed by radioimmunoassay (RIA) in multiple serum samples drawn over 30 min, showed hCG to have a long half-life, whereas ashCG was cleared very rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  R. Hoermann,et al.  Carbohydrate modifications transform human chorionic gonadotropin into a potent stimulator of adenosine 3',5'-monophosphate and growth responses in FRTL-5 thyroid cells. , 1991, Endocrinology.

[2]  R. Hoermann,et al.  Design of a long-lived thyrotropin antagonist from derivatives of human chorionic gonadotropin. , 1989, Endocrinology.

[3]  R. Hoermann,et al.  Evidence that partially desialylated variants of human chorionic gonadotropin (hCG) are the factors in crude hCG that inhibit the response to thyrotropin in human thyroid membranes. , 1988, Endocrinology.

[4]  K. Kasagi,et al.  The role of subunit sialic acid in the thyrotropic and gonadotropic activities of human chorionic gonadotropin. , 1987, Endocrinology.

[5]  R. Osathanondh,et al.  Divergent responses by human and mouse thyroids to human chorionic gonadotropin in vitro , 1985, Molecular and Cellular Endocrinology.

[6]  R. Osathanondh,et al.  Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole , 1984 .

[7]  Y. Shimohigashi,et al.  Role of the carbohydrate moiety of human choriogonadotropin in its thyrotropic activity. , 1984, Archives of biochemistry and biophysics.

[8]  Y. Shimohigashi,et al.  Sialic acid residues of the α-subunit are required for the thyrotropic activity of hog , 1982 .

[9]  S. Amir,et al.  The effect of desialylation on the in vitro interaction of human chorionic gonadotropin with human thyroid plasma membranes. , 1981, Endocrinology.

[10]  S. Amr,et al.  A competitive antagonist of thyrotropin: asialo-choriogonadotropin. , 1980, Biochemical and biophysical research communications.

[11]  B. Nisula,et al.  Thyroid function in gestational trophoblastic neoplasia: evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma. , 1980, American journal of obstetrics and gynecology.

[12]  S. Amir,et al.  In vitro responses to crude and purified hCG in human thyroid membranes. , 1980, The Journal of clinical endocrinology and metabolism.

[13]  P. Carayon,et al.  Interaction of human chorionic gonadotropin and human luteinizing hormone with human thyroid membranes. , 1980, Endocrinology.

[14]  O. P. Bahl,et al.  Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action. , 1975, The Journal of biological chemistry.

[15]  J. Hershman,et al.  The thyrotropin in hydatidiform moles is human chorionic gonadotropin. , 1975, The Journal of clinical endocrinology and metabolism.

[16]  K. Catt,et al.  Ovarian binding of intact and desialytated hcg in vivo and in vitro. , 1972, Endocrinology.

[17]  K. Catt,et al.  Biological properties of hCG after removal of terminal sialic acid and galactose residues. , 1972, Endocrinology.

[18]  G. Ross,et al.  Effects of progressive desialylation on the rate of disappearance of immunoreactive HCG from plasma in rats. , 1971, Endocrinology.

[19]  G. Ross,et al.  Immunological and biological activity of HCG following progressive desialylation. , 1971, Endocrinology.

[20]  J. Mckenzie.  The bioassay of thyrotropin in serum. , 1958, Endocrinology.

[21]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.