Sheep Thyroid Slices Research Articles

The uptake of [ 35S]methimazole by sheep thyroid slices in vitro

The uptake of [ 35S]methimazole by sheep thyroid slices has been shown to be activated in the presence of iodide. The total uptake ( Q) of [ 35S]methimazole was shown to be the sum of a saturable process and a non-saturable process. The constants Q max, K s and P in the two-term equation were determined using a published statistical method and a Fortran IV computer programme. Diiodotyrosine (DIT) at a 0.1 mM concentration stimulated the saturable uptake of [ 35S]methimazole appreciably in the absence of iodide, whilst thyroid-stimulating hormone (TSH) inhibited uptake in the presence of iodide and was of no effect in the absence of iodide. Propylthiouracil (PTU) inhibited the saturable uptake of [ 35S]methimazole whilst perchlorate had no effect.

Inhibition by Iodide of the Activation of the Thyroid Cyclic 3′,5′-AMP System

The action of iodide on the cyclic AMP system of dog thyroid slices has been studied. Iodide inhibits the enhancement of cyclic AMP accumulation in the presence of TSH. Such an effect is also observed in horse, beef and sheep thyroid slices, but not in dog kidney slices stimulated by parathyroid hormone or in rat parotid slices stimulated by isoproterenol. The effect in dog thyroid slices is suppressed by 1mM NaClO4, 1mM methimazole and 1mM propylthiouracil. Similar data have been obtained for prostaglandin E1 stimulation. Effects of thyrotropin mediated by cyclic AMP, i.e., activation of iodothyronine secretion, 1-14C-glucose oxidation, and lactate formation, were also inhibited by iodide but not by iodide and methimazole. Similar activations when caused by dbcAMP were not inhibited by iodide. The data suggest a model in which an intracellular agent resulting from the oxidation of iodide acts on the thyroid cyclic AMP system.

Iodinated thyrolipids: their possible role in homonogenesis.

ABSTRACT A total of 42 human thyroid glands (nodular goitre 9, adenoma with cystic degeneration 6; toxic goitre 10; carcinoma 14; and normal thyroid gland 3) were examined in vitro for iodination of an unidentified polar non-phosphatide lipid fraction (fraction II). The radioiodine incorporation in fraction II was 49.3 %, 43.6 %, 32.8 %, 20.7 %, and 22.0 % respectively in normal, nodular goitre, adenoma with cystic degeneration, toxic goitre and thyroid carcinoma. In vitro studies with surviving sheep thyroid slices did not show any relation between the iodination of fraction II and thyroxine formation over a period of 120 min. However, a highly significant correlation (r-value= 0.96375) was observed between the iodination of fraction II and thyroxine formation in vivo in the rat thyroid gland over a period of 24 h. We have previously postulated that iodination of fraction II may be interrelated to thyroxine formation. In the light of this hypothesis and the above results we suggest that the iodination of fraction II and thyroxine formation in the thyroid gland may be interrelated, the degree of iodination of fraction II being modulated by the amount of thyroxine formed within the thyroid gland.

Further studies on the 27S and 32S optical density peaks of the rat thyroid.

ABSTRACT In this paper evidence is presented that a 27S Optical Density (O. D.) peak is absent and a 32S O. D. peak is regularly present on analysis of the soluble thyroid proteins of the goitrous rat. This occurs irrespective of the goitrogenic stimulus and a normal O. D. pattern can be restored by reversal of the goitrous process by thyroxine. In rats rendered goitrous by a low iodine diet or KClO4 treatment, iodine supplementation also removed the 32S O. D. peak and resulted in reformation of the 27S peak. In rats treated by antithyroid drugs of the thiocarbamide group loss of the 32S O. D. peak was not associated with recovery of a 27S peak. This may be related to differences in potency of the various antithyroid drugs. 125I and 3H-leucine were not incorporated into the 32S O. D. peak material of the rat thyroid in vivo or into the 32S O. D. peak material of sheep thyroid slices in vitro. The view that this 32S O. D. peak was not iodoprotein nature was confirmed by showing that this peak had a maximal absorbance at 260 nm favouring the hypothesis that it was composed of nucleic acid.

Effects of thyrotropin, sodium fluoride and ions on thyroid slice metabolism

Activation of adenyl cyclase with resultant formation of cyclic 3′, 5′-AMP has been implicated in the action of thyrotropin (TSH) on thyroid. Since sodium fluoride increases adenyl cyclase activity in thyroid and also stimulates thyroid slice glucose oxidation and phospholipogenesis, we compared the effects of TSH and fluoride, singly and in combination, on glucose-1- 14C oxidation and 32P incorporation into phospholipid in sheep thyroid slices. Although these effects were superficially alike, and were similarly affected by changes in the ionic composition of the incubation medium, no synergism between TSH and fluoride effects was noted and stimulation induced by maximal effective concentrations of NaF was augmented by the addition of TSH. These data suggest that the sites at which these compounds interact on the thyroid to exert their effects are different. The significance of these findings in relation to the possible role of the adenyl cyclase-cyclic 3′, 5′-AMP system in controlling thyroid metabolism is discussed.

Thyroid cytoplasmic ribonucleoprotein particles of very high size containing messenger-like and ribosomal ribonucleic acids.

Cytoplasmic giant‐size ribonucleoprotein particles has been purified from the deoxycholate treated 15000 ×g supernatant of sheep thyroid slices incubated in the presence of [3H]uridine for 0.5 to 8 hours. After treatment of unclarified polyribosomes with 10 mM EDTA, 400 to 1000 S ribonucleoprotein particles have been isolated free of ribosomal subparticles by differential sedimentation. They are heterogeneous in size and buoyant density in CaCl gradients (from 1.38 to 1.52 g/ml, with maxima at 1.52, 1.46, and 1.42).Polyribosome‐associated 400 to 1000 S ribonucleoprotein particles deprived of free ribosomal subparticles contain messenger‐like and ribosomal RNA as shown by the rate of labelling and sucrose gradient centrifugation, polyacrylamide gel electrophoresis and base composition.Particle proteins obtained by 3 M LiCl‐6 M urea treatment separate in polyacrylamide gel electrophoresis into 3 to 4 basic components which disclose the same electrophoretic mobility as some ribosomal proteins. These 3 to 4 protein bands are distinct from total thyroid soluble proteins and from histones. Similar protein species are present in ribonucleoprotein particles diffusing spontaneously from thyroid nuclei in vitro.The artifactual formation of these structures during EDTA exposure or slice incubation has been rendered unlikely by appropriate controls. Although tentative, the possible physiological significance of these particles is briefly discussed.

Effects of adrenergic blocking agents on basal and stimulated thyroid function

Thyrotropin (TSH) effects on thyroid are believed mediated via activation of adenyl cyclase. Since adrenergic blocking agents inhibit thyroid adenyl cyclase, we studied their effects on glucose oxidation and phospholipogenesis in sheep thyroid slices. Propranolol (PPL) and phentolamine (PH), 10 −4 M, abolished TSH- and dibutyryl cyclic-AMP-induced increases in glucose oxidation but lesser [physiologic] concentrations of PPL and PH, i.e., 10 −6 M, were without effect. Basal glucose oxidation was not appreciably altered by these drugs. Both PPL and PH (5 × 10 −4 M) abolished TSH- and dibutyryl cyclic-AMP-induced endocytosis within the thyroid cell. These data suggest a mechanism other than adenyl cyclase inactivation for the inhibitory effect of these drugs on stimulated thyroid glucose oxidation. PPL and PH, 10 −4 M, stimulated basal phospholipogenesis. Submaximal concentrations of these drugs augmented maximal effective concentrations of TSH or dibutyryl cyclic-AMP in 32P incorporation studies indicating different mechanisms of thyroid stimulation. These data also indicate that phospholipogenesis in thyroid is unrelated to adenyl cyclase activation or endocytosis. This study suggests due caution in the use of adrenergic blocking agents to study the role of adenyl cyclase in thyroid stimulation.

The cell membrane: A common site of action of thyrotropin (TSH) and long-acting thyroid stimulator (LATS)

We have recently shown that the initial interaction of both thyrotropin (TSH) and long-acting thyroid stimulator (LATS) with the thyroid is rapid, firm binding to a superficial cell site, possibly the cell membrane. In order to evaluate those structural features of the cell membrane requisite for hormonal action in the present study, sheep thyroid slices were treated with phospholipase C, which is known to affect membrane phospholipids, and the subsequent response to TSH or LATS as measured by 32P incorporation into phospholipids was examined. Phospholipase C (5–25 μg./ml.) abolished this response although basal and acetylcholine-stimulated phospholipogenesis were unaffected. Thus, a membrane phospholipid appears important for the action of both TSH and LATS on the thyroid cell. Since phospholipid may play an important role in membrane transport of ions, the effects of cations and ouabain on TSH and LATS stimulation of 32P incorporation into sheep thyroid slice phospholipid were studied. Omission of Na + from the buffer markedly decreased base-line incorporation and abolished the response to both stimulators. Addition of 12 mM Na + restored TSH and LATS action without increasing base-line incorporation. Ca ++ and Mg ++ were not essential for TSH or LATS stimulation of 32P incorporation. Ouabain (10 −4 M) abolished the effects of both stimulators on phospholipogenesis. These findings indicate that both TSH and LATS stimulation of 32P incorporation into phospholipids have an absolute dependence on Na + and are similarly influenced by the ionic composition of the medium. It would thus appear that despite their marked physico-chemical and immunological differences, the in vitro effects of both stimulators are mediated in similar fashion, presumably via interaction with the thyroid cell membrane.

The immunoglobulin G (IgG) of Graves' disease: thyroid stimulation by fraction and fragment.

The differing time-course of thy-roidal 13lI release effected by pituitary thyro-tropin (TSH) and the long-acting thyroid stimulator (LATS) of Graves’ disease in the mouse bioassay is believed due to the longer half-life of LATS in the circulation. Since papain or pepsin digestion of LATS-IgG yields protein fragments which resemble TSH with respect to duration of their thyroid-stimulating properties in vivo, we compared the effects of LATS-IgG, peptide fragments obtained from proteolysis of LATS-IgG and TSH on glucose oxidation in sheep thyroid slices. Thyroid slices were incubated with either LATS-IgG, LATS-IgG papain digest, or LATS-IgG reduced pepsin digest, concentration 0.5−2.0 mg/ml, or with TSH 0.5 U/ml, in buffer containing glucose-1-14C at 37 C for periods ranging from 15 min to 3 hr. Although these concentrations of LATS-IgG did not effect a significant increase in 14CO2 production (mean response in 20 experiments = 99% of control ±10.5 sd), both papain and reduced pepsin digests significantly a...

Failure of theophylline to potentiate stimulated thyroidal glucose oxidation and phospholipogenesis.

Theophylline, a cyclic nucleotide phosphodiesterase inhibitor, at concentrations of 25–100 μg/ml stimulated glucose oxidation and phospholipogenesis in sheep thyroid slices. No dose-response relationship was evident and theophylline at 500 μg/ml significantly reduced glucose-l-14C oxidation and 32P incorporation into phospholipids. Ineffective concentrations of theophylline (10 μg/ml) consistently potentiated subliminal cyclic 3′,5′-adenosine monophosphate (C-AMP) stimulation of thyroidal phospholipo-genesis, whereas little or no interaction was evident with other adenosine phosphates or cyclic nucleotides. However, no positive interaction between theophylline and submaximal doses of thyrotropin (TSH) or long-acting thyroid stimulator (LATS) was demonstrable in either glucose oxidation or 32P incorporation studies and the effects of maximal doses of these stimulators on thyroidal phospholipogenesis were inhibited by theophylline. Although these data are at variance with the results of previous studies of ...

Comparative effects of thyrotropin and long-acting thyroid stimulator on thyroidal intermediary metabolism: Relationship to pyridine nucleotide levels

Both thyrotropin (TSH) and the long-acting thyroid stimulator (LATS) of Graves' disease stimulate glucose oxidation and phospholipogenesis in sheep thyroid slices. TSH (0.2–0.5 USP U./ml.) effected a 22–39 per cent mean increase in 14CO 2 production from glucose-1- 14C while LATS (2–4 MRC mU./ml.) caused a 28–32 per cent mean increase in glucose oxidation. Lesser concentrations of both stimulators (TSH, 10–50 mU./ml.; LATS, 0.5–2 MRC mU./ml.) were required for significant augmentation of 32P incorporation into thyroidal phospholipids. Varying the incubation time from 1–6 hr. did not differentially alter TSH or LATS effects on 14CO 2 production or 32P incorporation in thyroid slices. Measurement of thyroidal pyridine nucleotides (PN) under these circumstances indicates little or no correlation between stimulator-induced changes in NAD NADH or NADPH NADP ratios on the one hand and augmentation of either glucose oxidation or phospholipogenesis on the other. Although dibutyryl cyclic 3′, 5′-adenosine monophosphate mimics the effects of TSH and LATS on thyroidal glucose oxidation and phospholipogenesis, the concomitant alterations seen in PN levels (increased NADH, NADPH) were entirely unlike those seen with either stimulator. These findings confirm the dissociation between changes in thyroidal PN and augmentation of intermediary metabolism within the gland.

Effects of cyclic 3',5'-adenosine monophosphate and dibutyryl cyclic 3',5'-adenosine monophosphate on basal and stimulated thyroid function.

ABSTRACT Evidence has been presented (1, 2) that the effects of thyrotropin (TSH) and long-acting thyroid stimulator (LATS) on thyroid iodine uptake and discharge may be mediated by cyclic 3′,5′-adenosine monophosphate (C-AMP). Although dibutyryl C-AMP (DBC), concentration 5 mg/0.5 ml, consistently stimulated 131I release in the mouse bioassay in the studies reported herein, addition of the cyclic nucleotide to diluted LATS serum resulted in modest but significant reduction in the bioassay response to the abnormal stimulator. Since both TSH and LATS stimulate thyroidal glucose oxidation and phospholipogenesis, we studied the effects of C-AMP and DBC on 14CO2 production from glucose-1-14C and 32P incorporation into phospholipids in sheep and dog thyroid slices. C-AMP (100–500 μg/ml) failed to increase glucose-1-14C oxidation but DBC at 150–250 μg/ml was active (mean increase 20%). C-AMP at 250–500 μg/ml had a variable stimulatory effect on phospholipogenesis (5/8 experiments, mean increase 16%); BDC at 50–...

Glycoprotein biosynthesis in sheep thyroid slices incubated with radioactive glucosamine and leucine. I. Polysomes, microsomes and postmicrosomal fraction.

The subcellular site of carbohydrate incorporation into protein and thyroglobulin was investigated in sheep thyroid slices incubated in the presence of [i-14C]-glucosamine, galactose or mannose and of [4,5-3H2]leucine. 1.1. After establishing appropriate methods for DNA and RNA determination in the presence of thyroglobulin, conditions were selected for the subcellular fractionation of thyroid tissue. Polysomes with a high [3H]leucine label were obtained by different methods; their yield, polymerisation level and purity were estimated.2.2. Sucrose density gradient centrifugation of microsomal and supernatant extracts showed that a high proportion of labeld proteins was represented by thyroglobulin. Light precursors of thyroglobulin present in the supernatant appeared to be almost unlabeled by [14C]glucosamine whereas fully-sized S ∼- 18 thyroglobulinwas markedly labeled; this suggested a late process of carbohydrate attachment.3.3. Deoxycholate-soluble fractions of microsomes (vesicle content plus bounding membranes) were found to be a site of [14C]carbohydrate incorporation into proteins at a time when such an incorporation was not detected on purified polysomes. A definite trichloracetic acid-insoluble [14C]carbohydrate label appeared on polysomes with longer incubations, but the [14C]carbohydrate/[3H]leucine disint./min ratio of polysomes was several times smaller than that of deoxycholate-soluble microsomal fraction. A parallelism was observed between the [14C]carbohydrate label of polysomes and their protein/RNA ratio, suggesting relocation of labeled proteins.4.4. This relocation was confirmed by slice incubation in the presence of puromycin: [3H]leucine incorporation was almost entirely suppressed, while the [14C]-carbohydrate incorporation inculding the polysomal label, was only partially inhibited. Glycosylation therefore appears to occur after polypeptide synthesis and to take place on proteins enclosed within microsomal membranes rather than on nascent ribosomal peptide chains.

Glycoprotein biosynthesis in sheep thyroid slices incubated with radioactive glucosamine and leucine. II. A study of microsomal subfractions.

Synthesis of the thyroglobulin polypeptide portion is known to precede a particle-located stepwise attachment of carbohydrates, and polysomes, contrary to microsomal membranes, do not appear to be involved in glycosylation. The labeling of sheep thyroid microsomal subfractions (where thyroglobulin is the major labeled protein) has been investigated here and we have tried to correlate protein intracellular transport with glycosylation. 1.1. Rough and smooth microsomes were prepared with Cs+ essentially as described by Dallner for liver. Chemical and electron-microscope controls pointed to a relative separation.2.2. Thyroid slices were pulse-labeled with [3H]leucine and further incubated in a chase medium, for up to 4 h. A rapid transfer of protein-bound label was found to occur from ribosomes to the deoxycholate-soluble fraction of rough microsomes (including bounding membranes and vesicle contents), but no transfer from this fraction to smooth microsomes was observed. Lack of postmicrosomal supernatants showed that secretion of protein from the endoplasmic reticulum to the colloid occurred at a show rate.3.3. When slices were incubated with [14C]glucosamine, both rough and smooth microsomes were found to be labeld. Specific radioactives of protein-bound glucosamine and sialic were higher in rough than in smooth microsomes. Results suggest that glycosylation occurs within the membranes of the whole endoplasmic reticulum rather than only within the Golgi elements.

Effects of iodotyrosines on basal and stimulated glucose oxidation and phospholipogenesis in sheep thyroid slices.

We have studied the effects of mono- and diiodotyrosine (MIT, DIT) on basal and stimulated glucose oxidation and 32P incorporation into phospholipids in sheep thyroid slices to evaluate the interrelationship between these metabolic effects and to see if iodotyrosines altered the response to thyrotropin (TSH) or long-acting thyroid stimulator (LATS). MIT and DIT (25–500 μg/ml) increased glucose-l-14C oxidation by 49 and 29%, respectively. Stimulation of 32P incorporation was less marked (14 and 9% mean increase, respectively) and more variable. In neither instance was a doseresponse relationship seen. Both MIT and DIT potentiated submaximal TSH effects on thyroidalthyroidal glucose oxidation but did not augment similar LATS effects. Neither submaximal TSHnor LATS-stimulated 32P incorporation was augmented by MIT-DIT. Since iodotyrosine stimulation of glucose oxidation in thyroid is believed due to generation of NADP, the divergent effects of MIT-DIT on thyroidal glucose oxidation and phospholipogenesis ind...

Inhibition of thyroidal iodotyrosine deiodination by tyrosine analogues.

The effect of several tyrosine derivatives on deiodination of 3,5-diiodo-L-tyrosine (DIT) has been examined in vitro and in vivo. In TPNH-supplemented sheep thyroid homogenates, the most effective inhibitors of deiodination, in order of increasing potency, were 3,5-dibromo-L-tyrosine (DBT), 3,5-dinitro- L-tyrosine (DNT) and 3-nitro-L-tyrosine (MNT); kinetic studies suggested purely competitive inhibition. Compounds with weak or no inhibitory activity included tyrosine itself, its 3-methyl-, 3-isopropyl-, 3-ra-propyl-, and 3- amino- derivatives, and 3,4-dihydroxy-L-phenylalanine. DBT, DNT and MNT also inhibited deiodination of DIT by sheep thyroid slices. In rats, administration of DBT, DNT, or MNT with 131I-DIT inhibited deiodination, and led to the appearance of an unknown DIT metabolite in blood and urine. Administration of the most potent in. vitro inhibitor, MNT, to rats prelabeled with radioiodine was followed by the urinary excretion of large amounts of a similar unknown organic iodine compound, together with small amounts of DIT and of monoiodotyrosine. This result suggests that MNT can inhibit the deiodination of endogenously formed iodotyrosines. (Endocrinology83: 336, 1968)

Effects of inorganic iodide on thyroid stimulation in vitro.

Both pituitary thyrotropin (TSH) and the long acting thyroid stimulator (LATS) of Graves’ disease stimulate glucose oxidation and 32P incorporation into phospholipids in thyroid slices. Since inorganic iodide has been shown to stimulate intermediary carbohydrate metabolism in thyroid slices, studies were done to determine whether the effects of TSH and/or LATS on thyroidal glucose oxidation and phospholipogenesis were modified by the presence of iodide in the medium. Nal in concentrations (1.7 × 10−3m, 3.3 × 10−4m) which either stimulated or were without effect on oxidation of glucose-l-14C or 32P incorporation into phospholipids by sheep thyroid slices consistently inhibited TSH-induced stimulation of thyroidal glucose oxidation and phospholipogenesis. The same concentrations of Nal did not affect, and in a few instances augmented, LATS-induced stimulation of thyroidal glucose oxidation and 32P incorporation. Increased glucose oxidation in dog thyroid slices was observed when the gland was removed after ...

Messenger ribonucleic acids of the thyroid gland. I. Rapidly-labelled RNA of nuclei and polysomes

Nuclear and cytoplasmic RNA from sheep thyroid slices in vitro labeled with [3H]uridine or [32P]phosphate from 5 min up to 9 h, have been obtained by different phenol extraction procedures. Early‐labeled RNA was only extracted by phenol containing 0.1 or 1% (w/v) sodium dodecylsulfate (SDS) at 0° or 60°, whereas stable nuclear or polysomal RNA was easily extracted by pherol at 0°. Time course of incorporation of label into subcellular particles has shown the early labeling of nuclear RNA and the transfer of radioactivity into the cytoplasm. Rapidly‐labeled RNA extracted from nuclei by phenol‐1% (w/v) SDS and analyzed by sedimentation was shown to sediment in three discrete classes 50–30S, 22 S and 13 S, different from ribosomal RNA. After 9 h of incubation the 22 S and 13 S labeled RNAs were still present in detectable amounts in the nuclei, indicating a somewhat low turnover rate for these components. The kinetics of incorporation of label into polysomes was studied in thyroid slices incubated from 15 min up to 5 h with [3H]uridine or [32P]phosphate. RNA was dissociated from polysomes by dodecylsulfate treatment and centrifuged on sucrose gradient. As for nuclei, the rapidlylabeled RNAs sediment in discrete size classes, 22 S and 13 S. After a long incubation time (5 h) the label was predominant in 28 S and 18 S ribosomal RNA but 28 S RNA was not completely labeled. Up to 30 min labeling a high molecular weight, early‐labeled RNA was present in purified polysomes. Its radioactivity declines after 60 min labeling. A part of the rapidly labeled polysomal RNA can be reversibly separated from rRNP by the action of EDTA (1.25 to 5 μ moles EDTA/mg RNP). It sediments in a broad zone (12–30 S) of high specific radioactivity. Increasing Mg++ concentration results in the reassociation of rapidly‐labeled RNA to ribosomal sub‐particles. Buoyant densities of the polysomal RNP particles obtained by EDTA treatment of 32P‐labeled polysomes and stabilized by means of formaldehyde fixation, were determined by banding in CsCI gradients. The bulk of the stable material banded at characteristic densities (d= 1.55 and 1.48), but most of the rapidly‐labeled RNA banded at d= 1.38. The specific radioactivity of this material was the same as that of the 12–30 S RNA isolated by sucrose gradient centrifugation from the same EDTA‐treated polysomes. Preliminary double labeling experiments and computation of the RNA to protein ratio calculated from the RNA and protein density values indicate this material to be early‐labeled nucleoprotein particles with a high protein content.

Influence of mitochondrial inhibitors on the respiration and energy-dependent uptake of iodide by thyroid slices.

The influence of mitochondrial inhibitors, including oligomycin, antimycin and rotenone, on the iodide and oxygen uptake and the nucleotide content of incubated sheep thyroid slices was investigated. Each inhibitor strongly suppressed both iodide and oxygen uptake, and decreased the nucleoside triphosphate content of the slices. In most cases the addition of glucose or mitochondrial substrates restored iodide uptake in inhibitor-treated slices. Inhibitor concentrations sufficient to inhibit iodide uptake strongly had only slight effects on the thyroidal Na(+)+K(+)-activated adenosine triphosphatase. It is concluded that the inhibitors produce their effects by the inhibition in vivo of mitochondrial oxidative phosphorylation. ATP synthesis appears to be essential for iodide uptake to occur, and the high-energy intermediates (or energized state) of oxidative phosphorylation cannot be used to energize the uptake process. To a limited extent glycolytic ATP synthesis can support iodide uptake, which is therefore not exclusively dependent on aerobic metabolism. The mechanism of energy-linked iodide uptake is discussed.

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)