Interaction of Human Chorionic Gonadotropin and Human Luteinizing Hormone with Human Thyroid Membranes

Abstract

In an attempt to identify a possible pathogenetic role for the hCG molecule in the mechanism of the hyperthyroidism which occurs in choriocarcinoma, we have looked for evidence that the hCG molecule has a thyrotropic action on the human thyroid. The thyrotropic activity of various hCG preparations on the human thyroid was assessed by measuring the stimulation of adenylate cyclase activity in human thyroid plasma membranes purified by sucrose density gradient centrifugation. The highly purified hCG CR119 preparation stimulated human thyroid adenylate cyclase activity. Its activity was more than 654 times greater than could be accounted for by human TSH (hTSH) contamination of the preparation, as determined by RIA. The thyrotropic activity intrinsic to 1.0 IU hCG was equivalent to roughly 0.27 microU hTSH. Significant saturable binding of the 125I-labeled highly purified hCG preparation to human thyroid membranes was demonstrated, and the bound component was characterized. Its apparent molecular size, subunit composition, and testis receptor-binding characteristics were those of the hCG molecule. Examination of a crude urinary hCG preparation in adenylate cyclase and TSH radioligand assays using human thyroid membranes showed no evidence of any molecule other than hCG with a thyrotropic action on the human thyroid. Given that hCG binds to and stimulates adenylate cyclase activity in human thyroid tissue, as the above data indicate, then human LH (hLH) would be expected to do the same, since hLH and hCG have such strong structural and functional similarities. As anticipated, a highly purified hLH preparation exhibited TSH binding inhibition and adenylate cyclase stimulation. Its activity was more than 1030 times greater than could be accounted for by hTSH contamination of the preparation. The thyrotropic activity intrinsic to 1.0 IU hLH was equivalent to roughly 44 microU hTSH. Thus, in addition to other shared properties, the hLH molecule and the hCG molecule share the ability to interact with human thyroid tissue. These results strongly indicate that the hCG molecule has a thyrotropic action on the human thyroid and support the hypothesis that hCG is the thyrotropic factor that mediates the hyperthyroidism which occurs in patients with hCG-secreting neoplasms.

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

“…The choice of a suitable animal model appeared to be difficult, because a substantial species-related variation in thyroid response to hCG is well known. Thus, intact hCG from pregnancy sources is a stimulator of significant potency in the rodent thyroid in vitro and in vivo (45)(46)(47)(48), whereas in the human thyroid it was reported to exhibit little, if any, thyrotropic activity (49)(50)(51). Moreover, desialylation and deglycosylation of hCG increase its agonistic activity measured by cAMP response in rat thyroid cells (FRTL-5) rather than transforming it into a pure antagonist like in the human thyroid (18).…”

Thyroid-Stimulatory Effects of Human Chorionic Gonadotrophin in Early Pregnancy

“…Even in the absence of frank hyperthyroid ism, changes in thyroid function tests have been noted in these patients [3,4], The thyroid-stimulatory activity released from these tumours is identical to that of hCG [5]. The hormone has been shown to interact with thy roid cells in culture, competing with TSH for receptor binding sites [6] and stimulating the membrane-bound adenylate cyclase [7]. The potency of hCG as a thyroid stimulator is, however, said to be relatively low with between 10,000 and 40,000 U of hCG being equivalent to 1 mU of TSH with most in vitro assays [8][9][10], The relevance of hCG as a thyroid stimulator during normal pregnancy has, therefore, been questioned but needs to be re-examined in the light of modern thyroid function tests and bio-assay techniques.…”

Maternal Thyroid Function in Early and Late Pregnancy¹

“…In early pregnan cy, several studies have shown an increase in free thyroid hormone levels as compared to nonpregnant or postpar tum controls [1][2][3][4][5][6], with a concomitant decrease in serum TSH levels [2, 3. 6-8], These results have been related to the presence of elevated hCG levels, the intrin sic thyroid stimulating activity of which has been shown by several authors in various in vivo and in vitro bioas say systems [9][10][11][12][13][14][15], However, Amir et al [16,17] did not confirm hCG thyroid stimulating activity, at least on human thyroid tissue. Other studies of thyroid function in humans showed no modifications [18][19][20] or even a decrease [21,22] in free thyroid hormone levels in the presence of decreased [20.…”