Effects Of Long-acting Thyroid Stimulator Research Articles

Stimulation of thyroidal iodothyronine 5'-monodeiodinase by long-acting thyroid stimulator (LATS).

To evaluate the effect of long-acting thyroid stimulator (LATS) on thyroid iodothyronine monodeiodinating activity, we have studied the in vitro conversion of T4 to T3 by mouse thyroid homogenate comparing tissue from LATS treated (0.1 ml LATS(+) serum, ip, for 3 days) with tissues from LATS(-) Graves' disease patients' serum or normal serum treated controls. Five out of seven LATS(+) sera were shown to stimulate the T4 5'-deiodinase significantly in mouse thyroid. There was no significant correlation between LATS titre and deiodinase activities in the different sera tested. To compare the effect of LATS and TSH (0.2 IU, ip daily), studies were carried out from 12 to 72 h. LATS had a similar latency of 12 h on the stimulation of thyroid deiodinase compared to TSH as reported earlier. However, the conversion activities reached a plateau by 12 h after LATS treatment, while it continued to rise upon daily TSH injection from 24 to 72 h. In addition, TSH caused a marked reduction of thyroid protein and an early peaking in serum T3 and T4 at 12 h, whereas LATS caused no detectable change in thyroid protein and a gradual rise in circulating T3 and T4. The kinetic analysis indicated that LATS-mediated stimulation of T4 5'-deiodinase was, similar to TSH, associated with an increase in maximum velocity (Vmax were 139, 208 and 505 pmol/mg protein/30 min respectively in control, LATS and TSH-treated animals) without a demonstrable change in the apparent Km (approximately 2.0 microM for T4). The present study demonstrated that some LATS-rich sera stimulate thyroid T4 to T3 conversion in mouse. It provides an insight into the mechanism of increased T3 secretion from Graves' thyroid glands.

Effect of Long-Acting Thyroid Stimulator on Serum Concentration of Luteinizing Hormone in the Rat

1. The effect of long-acting thyroid stimulator (LATS) on the serum luteinizing hormone (LH) levels of the rat in pro-oestrus has been studied. 2. The injection of three out of four LATS-containing immunoglobulin G fractions caused an increase in amounts of serum LH. 3. Adrenalectomy and dexamethason suppression did not alter this response. 4. Injection of large doses of adrenocorticotrophic hormone did not produce any increase in serum concentrations of LH. 5. It is postulated that LATS may have a direct effect on the release of LH from the pituitary gland.

Effects of long-acting thyroid stimulator (LATS) and LATS protector on human thyroid adenyl cyclase activity.

The long-acting thyroid stimulator (LATS) has been thought to be responsible for the hyperthyroidism of Graves's disease. It is detected by its effect on the mouse thyroid gland but cannot be found in all patients with hyperthyroidism. In an attempt to clarify the problem of LATS-negative hyperthyroidism, serum was obtained from untreated patients and its effect in vitro on human thyroid tissue examined, using the activation of adenyl cyclase as a measure of stimulation. Human thyroid adenyl cyclase was activated by both thyroid-stimulating hormone (TSH) and LATS. Thyroid tissue obtained from patients with Graves's disease was relatively less responsive to LATS than was non-toxic thyroid tissue. Of the 24 samples studied five contained LATS and all of these activated adenyl cyclase. The presence of LATS protector in LATS-negative hyperthyroid patients was confirmed but LATS-negative sera had no effect on human thyroid adenyl cyclase activity.

Effects of long-acting thyroid stimulator on the reorganization into follicles of isolated thyroid cells and on the binding of radioiodinated thyrotropin to reassociated cells

Effects of long-acting thyroid stimulator on the reorganization into follicles of isolated thyroid cells and on the binding of radioiodinated thyrotropin to reassociated cells

Effects of Long-Acting Thyroid Stimulator on Thyrotropin Stimulation of Adenyl Cyclase Activity in Thyroid Plasma Membranes

Both thyroid-stimulating hormone (TSH) and long-acting thyroid stimulator (LATS) stimulated adenyl cyclase activity in plasma membranes obtained from bovine thyroid glands. The stimulation induced by LATS was much less than that obtained with maximal amounts of TSH. LATS inhibited TSH stimulation of adenyl cyclase activity while an equivalent amount of normal human gamma-globulin did not influence basal or TSH-stimulated activity. The inhibition by LATS appeared to be noncompetitive and was greatest when the plasma membranes were initially exposed to LATS for 30 min at 0 degrees C before being incubated with TSH for 10 min at 37 degrees C. Inhibition could still be demonstrated when the plasma membranes were incubated for 30 min at 0 degrees C with TSH before the addition of LATS. Prolonging the period of incubation of plasma membranes with LATS from 30 to 60 min did not augment the stimulation of adenyl cyclase or increase the inhibition of the effect of TSH. Papain digests of LATS also increased adenyl cyclase activity of thyroid plasma membrane and inhibited the stimulation induced by TSH. The inhibitory effect of LATS was not completely specific for TSH and thyroid plasma membranes since glucagon stimulation of adenyl cyclase in hepatic plasma membranes was also inhibited, but to a lesser extent. In contrast to the results obtained with thyroid plasma membranes, LATS did not influence basal adenyl cyclase activity in hepatic plasma membranes. Furthermore equivalent amounts of normal human gamma-globulin also decreased glucagon stimulation of adenyl cyclase activity in plasma membranes obtained from liver. The present data suggest that LATS stimulation of adenyl cyclase in thyroid plasma membranes might be due to a change in the membrane configuration rather than binding to a specific receptor site. Such modification of the membrane structure could interfere with the binding of TSH to specific receptors or to the subsequent stimulation of adenyl cyclase. However, the results do not exclude the possibility that some component in the preparation other than LATS might be responsible for the inhibition of the stimulation by TSH.

Effects of long-acting thyroid stimulator and prostaglandin antagonists on adenyl cyclase activity in isolated bovine thyroid cells

We studied the effects of long-acting thyroid stimulator [LATS] and two unrelated compounds reported to be prostaglandin antagonists, 7-oxa-13-prostynoic acid [PY 1] and polyphloretin phosphate [PPP] on adenyl cyclase activity in isolated bovine thyroid cells [ITC]. LATS-IgG stimulated ITC adenyl cyclase in a dose-related manner; the time-course of LATS-induced cyclase activation was comparable to that observed with thyrotropin [TSH] [onset at 5 min, maximal at 7.5 to 10 min]. PY 1, 5 μg/ml [≌ 1.4 × 10 −5M] and PPP, 5 μg/ml [≌ 3.3 × 10 −8M], significantly inhibited the stimulatory effects of prostaglandin E 2, TSH and LATS on ITC adenyl cyclase but did not modify basal cyclase activity. PPP, 0.5 mg, inhibited the effects of both TSH and LATS on mouse thyroid radioiodine release in vivo in an apparently competitive manner but did not modify dibutyryl cyclic AMP effects thereon. These studies suggest that activation of a prostaglandin receptor site may be an early step in the action of both LATS and TSH on thyroid.

In vitro effects of LATS and TSH on phosphodiesterase activity in human thyroid homogenates.

ABSTRACT The in vitro effects of long-acting thyroid stimulator (LATS) and thyrotrophin (TSH) on phosphodiesterase activity in human thyroid homogenates were studied. The enzyme activity was estimated by the destruction of 3H-cyclic 3′,5′-adenosine monophosphate. Bovine TSH had no effect on the enzyme activity. Five experiments were carried out using different batches of LATS-IgG and normal IgG which were preincubated with thyroid homogenates or not. There was no significant difference between the enzyme activity with LATS-IgG and that with normal IgG, while the activity was mostly inhibited by theophylline. These data are not consistent with the hypothesis that LATS acts as an antibody to phosphodiesterase.

Effects of long-acting thyroid stimulator on Escherichia coli.

Effects of long-acting thyroid stimulator on Escherichia coli.

Comparative effects of long-acting thyroid stimulator and pituitary thyrotropin on the intermediate metabolism of thyroid tissue in vitro.

Long-acting thyroid stimulator (LATS) increases the uptake and oxidation of glucose and enhances the formation of lactate by sheep thyroid slices in a manner analogous to the action of pituitary thyrotropin (TSH). LATS also increases phospholipogenesis (indicated by 32P incorporation), but the specificity of individual phospholipid response may be different from that with TSH. LATS stimulates the incorporation of 32P orthophosphate into lecithin and monophosphatidylinositol to about the same degree, whereas TSH action is directed mainly toward the latter phospholipid. In contrast to TSH, LATS consistently increases the labeling of neutral lipids from U-14C glucose, although their effects on decreasing the ratio of radioactive triglyceride/diglyceride are similar. (Endocrinology79: 949, 1966)