Effect of thyroid phospholipids on the interaction of thyrotropin with thyroid membranes.

Omodeo‐Salè, Fausta; Brady, Roscoe O.; Fishman, Peter H.

doi:10.1073/pnas.75.11.5301

Cited by 17 publications

(7 citation statements)

References 34 publications

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“…Other studies found no effect of added gangliosides on TSH binding when assayed under physiological conditions (21), in agreement with observations on the binding of human chorionic gonadotropin to testicular membranes (37). Thus, numerous studies (2)(3)(4)(5)20) have demonstrated that, under nonphysiological conditions, gangliosides can inhibit TSH binding to thyroid membranes, but this appears to involve the low-affinity site. When gangliosides are directly incorporated into thyroid cells, they do not cause increased binding under physiological conditions.…”

Section: Discussionsupporting

confidence: 69%

“…Other Methods. Mixed brain gangliosides were isolated from bovine brain and exhaustively purified to remove any contaminating phospholipids (5 ponents of FRTL cells were labeled by NaIO4 oxidation followed by NaB3H4 reduction, the same three gangliosides were observed to be labeled (Fig. 1).…”

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confidence: 99%

“…Gangliosides have been shown to inhibit TSH binding to thyroid plasma membranes (3)(4)(5)(6), and TSH has been shown to bind to liposomes containing gangliosides (7,8). Further, it has been demonstrated that the interaction of TSH with gangliosides leads to a perturbation in the TSH molecule (3,6) and that TSH also alters the membrane conductance oflipid bilayers containing gangliosides (9), analogous to the effects of cholera toxin on model membranes containing galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM,) (10)(11)(12).…”

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confidence: 99%

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Reevaluation of the role of gangliosides in the binding and action of thyrotropin.

Beckner¹,

Brady²,

Fishman³

1981

Proc. Natl. Acad. Sci. U.S.A.

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A cloned line of normal rat thyroid cells, FRTL, contained a small number of high-affinity binding sites for thyrotropin (TSH) when measured under physiological conditions. The cells also bound small amounts ofcholera toxin, and both hormone and toxin stimulated cyclic AMP production by the cells. The major ganglioside of FRTL cells was N-acetylneuraminylgalactosylglucosylceramide (GM3), with minor amounts of gangliosides corresponding to galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1) and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GD1,). Treatment of these cells with neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18) converted most of the GDIa to GM1. After neuraminidase treatment, the binding of cholera toxin, which binds to GM,, was increased, but there was no change in the binding of TSH. Preincubation of neuraminidase-treated FRTL cells with the B (binding) component of cholera toxin completely prevented cholera toxin binding but had no effect on the binding ofTSH. Neuraminidase treatment also somewhat enhanced, rather than decreased, the cyclic AMP response to TSH. Pretreatment of FRTL cells with mixed brain gangliosides resulted in a 10-fold increase in cholera toxin binding. (3,6) and that TSH also alters the membrane conductance oflipid bilayers containing gangliosides (9), analogous to the effects of cholera toxin on model membranes containing galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM,) (10-12). The ability ofcholera toxin to inhibit TSH binding to thyroid membranes (13) and the existence of homologous amino acid sequences in the a and A subunits and the 3 and B subunits of TSH and cholera toxin, respectively (3, 14), raised the possibility that both the hormone and the toxin may utilize gangliosides as receptors and have similar mechanisms of action (3, 13).Other studies have suggested that a glycoprotein is a component ofthe TSH receptor (7,(15)(16)(17). In this regard, Kohn has proposed that the TSH receptor is composed of both a glycoprotein and a ganglioside (17). According to his model, TSH, through its beta subunit, binds to the glycoprotein component of the receptor; then the hormone undergoes a conformational change whereby the alpha subunit penetrates the membrane and activates adenylate cyclase, these latter steps being mediated by the ganglioside component of the receptor (6,7,17 (20)(21)(22)(23). The recent availablity of a cloned, differentiated cell line derived from normal rat thyroid (24) prompted us to reexamine the role of gangliosides in TSH binding and action under physiological conditions.

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Section: Discussionsupporting

confidence: 69%

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confidence: 99%

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confidence: 99%

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Reevaluation of the role of gangliosides in the binding and action of thyrotropin.

Beckner¹,

Brady²,

Fishman³

1981

Proc. Natl. Acad. Sci. U.S.A.

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“…Several studies have provided evidence indicating that plasma membrane lipids in thyroid glands modulate the TSH receptor and its ability to bind TSH (Bashford et al 1975, Mehedi et al 1977, Omodeo-Sale et al 1978, Aloj et al 1979. Furthermore, an important role for phospholipids has been indicated in the TSHresponsive adenylate cyclase system (Macchia et al 1970, Yamashita et al 1970, Yamashita & Field 1973, Moore & Wolff 1974, Amir et al 1976.…”

Section: Treatment Without Epa-e (Days)mentioning

confidence: 99%

Effect of eicosapentaenoic acid ethyl ester on hypothyroid function

Miyamoto¹,

Oda²,

Miura³

et al. 2001

Journal of Endocrinology

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Thyroid hormones affect reactions in almost all pathways of lipid metabolism. It has been reported that plasma free fatty acid (FFA) concentration in hypothyroidism is generally within the normal range. In this study, however, we show that plasma FFA concentration in some hypothyroid patients is higher than the normal range. Symptoms of thyroid dysfunction in these individuals were less severe than those of patients with lower plasma FFA concentrations. From these findings we hypothesized that the change in FFA concentration must correlate with thyroid function. Using an animal model, we then examined the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E), a n-3 polyunsaturated fatty acid derived from fish oil, on thyroid function in 1-methyl-2-imidazolethiol (MMI)-induced hypothyroid rats. Oral administration of EPA-E inhibited reduction of thyroid hormone levels and the change of thyroid follicles in MMI-induced hypothyroid rats. These findings suggest that FFA may affect thyroid functions and EPA-E may prevent MMI-induced hypothyroidism.

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“…This possibilities has also been pointed out previously by Omodeo-Sale et al (1978). The ganglioside fractions containing two sialic acids per molecule are the most active fractions in inhibiting [125I]TSH binding to thyroid plasma membranes.…”

Section: Discussionmentioning

confidence: 62%

Presence of gangliosides in the structure of membrane receptor for thyrotrophin

Gardas

Nauman

1981

Acta Endocrinologica

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Thyroid gangliosides were isolated from bovine thyroid tissue. Neutral lipids and glycolipids were removed by chromatography on a DEAE-cellulose column and residual acidic phospholipids by alkaline degradation. Thyroid gangliosides were separated by chromatography on a silica acid column into 9 different fractions. Thyroid gangliosides were found to be active in the inhibition of [125I]TSH binding to thyroid plasma membranes and this results from a direct action between thyrotrophin and gangliosides. The most active fraction contained gangliosides with two sialic acids per molecule. Pre-incubation of thyroid plasma membranes for 4 hours at 37\s=deg\Cwith gangliosides and removal of the unbound gangliosides increased the [125I]TSH binding to pre-treated membranes by 10\p=n-\20%. Anti-ganglioside antibodies obtained by immunisation of rabbits inhibited [125I]TSH binding to thyroid plasma membranes by 60 to 80%. The thyroxine (T4) level in blood serum of immunized animals was significantly decreased after the first immunization and T4 become almost undetectable after the booster injection implying that antibodies against thyroid gangliosides produce severe impairment of thyroid cell function.

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Effect of thyroid phospholipids on the interaction of thyrotropin with thyroid membranes.

Abstract: Various lipids extracted from bovine thyroid glands were tested for their ability to affect the binding of -25I-labeled thyrotropin to bovine thyroid membranes.

Cited by 17 publications

References 34 publications

Reevaluation of the role of gangliosides in the binding and action of thyrotropin.

Reevaluation of the role of gangliosides in the binding and action of thyrotropin.

Effect of eicosapentaenoic acid ethyl ester on hypothyroid function

Presence of gangliosides in the structure of membrane receptor for thyrotrophin

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