Characterization of the Long-Acting Thyroid Stimulator of Graves' Disease

Meek, Joseph C.; Jones, A. E.; Lewis, U. J.; Vanderlaan, W. P.

doi:10.1073/pnas.52.2.342

Cited by 83 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been clearly established that LATS is a 7-S gamma globulin (1), but various techniques which have been used to disrupt the gamma globulins have given different results in terms of the time course of action of the resulting fragments. Meek, Jones, Lewis, and Van der Laan reported that after fractionation of the gamma globulins the peak effect was observed in 2 hr to be similar to that caused by TSH (17). Similar results were obtained by Dorrington, Carneiro, and Munro after papain digestion of LATS, whereas peptic digestion of the gamma globulin produced fragments which had the delayed effect characteristic of LATS (18).…”

Section: Resultssupporting

confidence: 74%

“…In most experiments measuring glucose oxidation, the effect of LATS did not exceed that of 0.5 mU of TSH. The in vivo effects of LATS are not inhibited by antibody to TSH, but are neutralized by antihuman gamma globulin antibody (1,(16)(17)(18). The data in Table V indicate that LATS stimulation of glucose oxidation is not abolished by anti-TSH antibody.…”

Section: Resultssupporting

confidence: 48%

See 1 more Smart Citation

In vitro stimulation by long-acting thyroid stimulator of thyroid glucose oxidation and 32P incorporation into phospholipids

Field¹,

Remer²,

Bloom³

et al. 1968

J. Clin. Invest.

View full text Add to dashboard Cite

AB s T R A C T Long-acting thyroid stimulator (LATS) increased glucose oxidation and 32P incorporation into phospholipids in in vitro experiments with dog thyroid slices. The time course of the response was different from that obtained with thyroid-stimulating hormone (TSH), but was very similar to the delayed effect observed in vivo. During a 45 min incubation, TSH, but not LATS increased glucose oxidation, whereas in longer experiments up to 6 hr, both substances augmented 14CO2 production. Amounts of pooled human gamma globulin equivalent to LATS were inactive. Although TSH stimulated 32P incorporation into phospholipids during a 2 hr incubation, LATS was ineffective. In longer incubations, from 41 to 8 hr. LATS did increase 32P incorporation.The stimulatory effect of LATS was not abolished by anti-TSH antibody capable of neutralizing human TSH. Effects of LATS were also obtained with beef and pig thyroid slices. In addition to stimulation of glucose oxidation in dog thyroid slices, LATS occasionally also stimulated glucose oxidation in dog spleen and liver slices. Despite a 54-fold increase in LATS concentration, a satisfactory dose-response curve could not be demonstrated when 14C02 production was measured.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Resultssupporting

confidence: 48%

In vitro stimulation by long-acting thyroid stimulator of thyroid glucose oxidation and 32P incorporation into phospholipids

Field¹,

Remer²,

Bloom³

et al. 1968

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The present study suggests that thyroid stimulating actiaity of LATS-IgG may be in Fab or Fab'-fragment, not in Fc fragment. Similar findings with peptic or papain digests of LATS-IgG were reported by Meek et al(1964) and Dorrington et al(1965).…”

Section: Immunofluorescent Localization Of Latssupporting

confidence: 78%

Comparative Studies on the Properties of LATS and TSH

Ochi

DeGroot

1970

Endocrinol Japon

View full text Add to dashboard Cite

LATS activity was neutralized by pretreatment of mice with anti-IgG in vivo. Simultaneous injection of epsilon-amino caproic acid and hydrocortisone does not inhibit LATS action. Human thyroid-microsomal fractions neutralize LATS activity and TSH activity. The decrease in activity of LATS and TSH caused by thyroid microsomes correlates positively. Calf thyroid microsomes are much less active than human thyroid microsomes in absorbing LATS activity. Deoxycholate and sonification solubilize the LATS neutralizing activity. No visible precipitate formed between these solubilized fraction and LATS-IgG, using the Ouchterlony agar diffusion method. LATS did not differ from TSH in heat stability, and partially heat denatured LATS still had a long acting type response. Dissociation of a small rapidly acting molecule from LATS could not be obtained in high molar NaCI solution. LATS-IgG fragments digested by proteolytic enzymes (papain, pepsin, trypsin, and ficin) had a prolonged response like LATS. However, these fragments, in the presence of cysteine, either gave the same response after 2 hr and 8 hr, or gave a short acting response like TSH. The thyroid stimulating active site of the LATS active gamma globulin may be situated in Fab or Fab fragments having the antibody combining site. LATS did not stimulate the chicken thyroid, although TSH had this action. The proteolytic fractions of LATS-IgG also did not stimulate the chicken thyroid. No increase of gammaglobulin and/or IgG was found in some sera with a high LATS activity. Binding of LATS-IgG to mouse or human thyroid could not be visualized using the Coon's immunofluorescent method. These data support the concept that LATS is an IgG having a high specific activity of thyroid stimulating action.

show abstract

“…An antibody has been defined as a "humoral globulin produced by the body in response to an antigen and capable of reacting with the antigen in some observable way" (17). The evidence appears strong that LATS is intimately associated with and perhaps identical to IgG, since it travels with IgG in all the usual electrophoretic and chromatographic procedures (2,3,18,19), is removed from serum by incubation with antihuman IgG (3,19), and can apparently be found in the heavy chain fraction formed by partial degradation of IgG (19).…”

mentioning

confidence: 99%