scholarly journals Evaluation of Small-Molecule Modulators of the Luteinizing Hormone/Choriogonadotropin and Thyroid Stimulating Hormone Receptors:  Structure−Activity Relationships and Selective Binding Patterns

2006 ◽  
Vol 49 (13) ◽  
pp. 3888-3896 ◽  
Author(s):  
Susanna Moore ◽  
Holger Jaeschke ◽  
Gunnar Kleinau ◽  
Susanne Neumann ◽  
Stefano Costanzi ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Small Molecule ◽  
Hormone Receptors ◽  
Thyroid Stimulating Hormone ◽  
Selective Binding ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Small Molecule Modulators ◽  
Stimulating Hormone

Effect of peptide nicking in the human chorionic gonadotropin β-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors

1994 ◽  
Vol 130 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Masayoshi Yoshimura ◽  
A Eugene Pekary ◽  
Xuan-Ping Pang ◽  
Loretta Berg ◽  
Laurence A Cole ◽  
...  
Keyword(s):  
Los Angeles ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Hormone Receptors ◽  
Thyroid Stimulating Hormone ◽  
Human Thyroid ◽  
Β Subunit ◽  
Trophoblastic Diseases ◽  
Thyrotropic Activity ◽  
Stimulating Hormone

Yoshimura M, Pekary AE, Pang X-P, Berg L, Cole LA, Kardana A, Hershman JM. Effect of peptide nicking in the human chorionic gonadotropin β-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors. Eur J Endocrinol 1994;130:92–6. ISSN 0804–4643 It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-β subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cyclic AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the β44–49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the β-intercysteine loop on recombinant human TSH receptors. These data suggest that peptide heterogeneity of the hCG molecule may modulate the in vivo thyrotropic activity of hCG in pregnant women and patients with trophoblastic diseases. Jerome M Hershman, Endocrinology-W111D, West Los Angeles VA Medical Center, Los Angeles, California 90073, USA

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