Search PubMed⌕ Search

Biomedical subjects

L D Kohn

Publications and source records attributed to L D Kohn.

At least 181 records · Page 10Linked to original sources
PubMed1986

Thyroglobulin gene activation by thyrotropin and cAMP in hormonally depleted FRTL-5 thyroid cells.

Thyroglobulin gene control by cAMP and thyrotropin has been compared in FRTL-5 thyroid cells maintained in the absence of serum, insulin, cortisol, and thyrotropin for 7 days. Readdition of thyrotropin induces an increase in the expression of the thyroglobulin gene with little effect on total RNA synthesis. In contrast, addition of 8-bromo cyclic AMP and cholera toxin stimulate total RNA synthesis as well as thyroglobulin gene expression. The same non-selective effect of cyclic AMP on the thyroglobulin gene was observed when transcriptional activity was measured in permeabilized FRTL-5 cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Characteristics of a lysosomal membrane transport system for tyrosine and other neutral amino acids in rat thyroid cells.

Tyrosine countertransport was used to demonstrate the existence of a carrier system for neutral amino acids in the lysosomal membrane of FRTL-5 thyroid cells. In addition to tyrosine, the carrier system recognized the neutral amino acids leucine, histidine, phenylalanine, and tryptophan. Cystine and lysine, amino acids for which a lysosomal carrier system has been demonstrated, showed no competition with tyrosine for countertransport. The tyrosine system showed stereospecificity and cation independence. It did not require an acidic lysosome or the availability of free thiols. The apparent Km for tyrosine was approximately 100 microM; the energy of activation of the system was approximately 9.7 kcal/mol. This new lysosomal membrane carrier system for neutral amino acids resembles the plasma membrane L system in 3T3 Chinese hamster ovary cells and melanoma B-16 cells.

Amino Acids↗
PubMed1986

Alpha 1-adrenergic stimulation of arachidonic acid release and metabolism in a rat thyroid cell line. Mediation of cell replication by prostaglandin E2.

The rat thyroid cell line, FRTL-5, expresses an alpha 1-adrenergic receptor when exposed to thyrotropin. We have found that occupation of this alpha 1-adrenergic receptor by norepinephrine stimulated the release of [3H]arachidonic acid from prelabeled cells. Arachidonic acid was metabolized primarily to prostaglandin E2 and to much smaller amounts of 11-hydroxy-5,8,11,13-eicosatetraenoic acid, 15-hydroxy-5,8,11,13-eicosatetraenoic acid, prostaglandin D2, and thromboxane B2. Synthesis of all these metabolites was inhibited by the cyclooxygenase inhibitor indomethacin. When FRTL-5 cells were starved of thyrotropin for 24 h, norepinephrine nearly doubled [3H]thymidine uptake into DNA. Cyclooxygenase inhibitors inhibited norepinephrine-stimulated thymidine uptake by 60-70%. Of several arachidonic acid metabolites tested, none was able to stimulate thymidine uptake directly in the presence of indomethacin. Prostaglandin E2, however, was able to restore [3H]thymidine uptake when added together with norepinephrine in the presence of indomethacin. Thus, occupation of an alpha 1-adrenergic receptor in a functional rat thyroid cell line leads to arachidonic acid release. Subsequent metabolism of the arachidonic acid by the cyclooxygenase pathway leads to synthesis of prostaglandin E2, which mediates a norepinephrine-stimulated activity related to cell replication.

Adrenergic alpha-Agonists↗
PubMed1986

Monoclonal antibody studies defining the origin and properties of autoantibodies in Graves' disease.

The present report summarizes experiments with monoclonal antibodies to the TSH receptor. The data provide further insight into the TSH receptor structure and into the basis of autoimmune antibodies implicated in the pathogenesis of Graves' disease. They resolve many clinical questions and provide new approaches to enhance our understanding of autoimmune disease. In one new approach, it has been noted that the 11E8 TBIAb can precipitate the phosphorylated beta subunit of the insulin and IGF1 receptor. This cross-reactivity or recognition of determinants adjacent to the TSH receptor may not be random. Insulin, IGF1, alpha 1 adrenergic, and TSH receptors have been linked to a synergistic cascade response system of the thyroid involving growth, thyroglobulin biosynthesis, iodination of thyroglobulin, and thyroid hormone formation. Future studies with the monoclonals may help unravel this cascade system and its regulatory relationships, along with the relationships between autoimmune thyroid disease and autoimmune diseases of other organs.

Antibodies, Anti-Idiotypic↗
PubMed1986

Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves' sera.

Immunoglobulin G (IgG) preparations from 17 of 20 hyperthyroid patients with Graves' ophthalmopathy stimulated collagen biosynthesis in human fibroblasts, as measured by [3H]proline incorporation. This activity was not associated with thyroid-stimulating antibody (TSAb) activity in a thyroid cell cAMP assay in 50% of the IgG preparations, and it was not found in IgGs from 12 normal subjects, 7 of 8 patients with Graves' hyperthyroidism but no ophthalmopathy, 4 patients with Hashimoto's disease, 7 patients with nontoxic goiter, or 4 hypothyroid patients. In the same assay, 11E8, 22A6, and 13D11, 3 mouse monoclonal antibodies to the bovine TSH receptor, and 307H6, a human monoclonal antibody to the TSH receptor of the thyroid from a Graves' patient with ophthalmopathy, also stimulated [3H]proline incorporation into collagen and were active at more than 1,000- to 10,000-fold lower IgG concentrations (0.1-0.5 microgram/ml as opposed to greater than 1 mg/ml). 11E8 and 13D11 are TSH binding inhibitory antibodies (TBIAbs); 22A6 and 307H6 are TSAbs in cAMP assays. Two other mouse anti-TSH receptor monoclonal antibodies, both TBIAbs, as well as 8 human monoclonal antibodies to the TSH receptor from Graves' patients with or without ophthalmopathy (2 TBIAbs and 6 TSAbs) were negative or significantly less potent (greater than 50 fold) in the assay. The fibroblast activity of the monoclonal antibodies was lost if the antibodies were preincubated with thyroid membranes, was significantly decreased when fibroblasts were exposed to mild trypsin treatment before the assay, was not inhibited by human asialoagalacto-thyroglobulin, and required more than a TSH receptor determinant, since TSH alone neither duplicated nor inhibited the antibody activity. In summary, an assay for measuring the activity of autoantibodies active in causing ophthalmopathy is described, and some but not all TSH receptor monoclonal antibodies have been found to duplicate the action of the autoimmune IgGs from the ophthalmopathy patients.

Adult↗
PubMed1986

Unusual antagonistic actions of mixtures of vasoactive intestinal peptide, thyroid-stimulating antibodies, and cholera toxin on adenosine 3',5'-monophosphate accumulation in normal human thyroid cell cultures.

When individually tested, vasoactive intestinal peptide (VIP), cholera toxin, and monoclonal thyroid-stimulating antibodies (TSAbs), but not TSH binding-inhibiting antibodies (TBIAbs), elevate cAMP levels in cultured human thyroid cells. In this study, we tested the effect on cAMP levels in human thyroid cells of the simultaneous presence of VIP and the other ligands noted. Monoclonal TBIAbs (11E8 and 122G3), which interact with a membrane glycoprotein containing the high affinity binding site of the TSH receptor, did not alter VIP-induced cAMP accumulation in the thyroid cells. These data indicate that VIP and TSH bind to distinct sites on the cell membrane. In contrast, monoclonal TSAbs 208F7 and 307H6, which interact with a portion of the TSH receptor other than its high affinity binding site, not only did not have their usual agonist activity, but, instead, caused a marked inhibition of human thyroid cAMP accumulation when VIP was also present. Mutual antagonism by two agonists, i.e. inhibition evident when TSAbs and VIP were mixed, was also found when cholera toxin was coincubated with VIP. The inhibitory effect of mixing cholera toxin and VIP was nearly immediate and was duplicated with mixtures of the beta-subunit of cholera toxin and VIP. The inhibition evident in mixing VIP and the TSAbs or cholera toxin was not duplicated in mixtures of isoproterenol and VIP or in mixtures of forskolin and VIP. These results suggest that the mutual inhibition of VIP and either TSAbs or cholera toxin is at a step that couples the TSH and VIP high affinity receptor-binding sites to the adenylate cyclase complex.

Antibodies, Monoclonal↗
PubMed1986

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Adenylyl Cyclases↗
PubMed1985

Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of alpha 1-adrenergic receptors in cultured rat thyroid cells.

Thyrotropin causes a time- and concentration-dependent increase in cytosolic Ca2+ in FRTL-5 rat thyroid cells as measured by Quin2 fluorescence; the half-maximal response occurs in response to 1 X 10(-7) M thyrotropin. The effect of added thyrotropin is the same whether cells have been previously and chronically exposed to thyrotropin or whether they have been thyrotropin "starved" for several days. The thyrotropin effect on cytosolic Ca2+ has no relationship to intracellular cAMP levels with respect to dose and time course. Norepinephrine (1 X 10(-7) M) also causes increases in cytosolic Ca2+ in FRTL-5 thyroid cells. With the use of a variety of adrenergic inhibitors, norepinephrine was found to exert its effect via an alpha 1-adrenergic receptor. The exposure of FRTL-5 cells to physiological thyrotropin concentrations enhances the effect on cytosolic Ca2+ level induced by norepinephrine in vitro; the shape of the dose-response curve indicates a cooperative effect of the thyrotropin and norepinephrine. The increase in cytosolic Ca2+ seems to be derived from an intracellular pool rather than from the extracellular space. It is not prevented by nifedipine, a blocker of Ca2+ channels; it is present in cells exposed to ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; and it is not associated with increased Ca2+ uptake into the cell. the thyrotropin- and norepinephrine-induced increase in cytosolic Ca2+ parallels the efflux of iodide and the organification of thyroglobulin in a dose-dependent manner.

Adrenergic alpha-Antagonists↗
PubMed1985

Thyrotropin interaction with high-density lipoproteins.

Human high-density lipoproteins (HDL), but not other lipoprotein classes, bind bovine thyrotropin (TSH) with moderately high affinity. Binding of 125I-labeled HDL to TSH has been measured in a solid-phase assay; it is saturable and can be displaced by unlabeled HDL but not by other lipoproteins or bovine serum albumin. The interaction of HDL with TSH has been studied by fluorescence spectroscopy: HDL specifically modifies the fluorescence properties of the biologically active dansyl derivative (DNS, (5-dimethyl-aminonaphtalene-1-sulfonyl) chloride) of TSH (DNS-TSH) causing a 12 nm shift to lower wavelength of the emission maximum, a two-fold increase of the quantum yield and a significant increase of fluorescence polarization. The primary site of TSH binding on the HDL particle is likely to be located on its protein moieties, since other lipoprotein classes, which share similar lipids with HDL, do not bind TSH. 125I-labeled apolipoprotein A-I binds TSH in the solid-phase assay and titration of DNS-TSH with apolipoprotein A-I causes perturbations nearly identical to those observed with intact HDL. One HDL particle has at least 12 binding sites for TSH with an association constant, K = 10(7) M-1 whereas one apolipoprotein A-I molecule binds one or two TSH molecules with an association constant slightly lower than that for HDL (K = 10(6) M-1). The lipid moieties of HDL also appears to be perturbed by the interaction with TSH.

Humans↗
PubMed1985

Thyrotropin upregulates alpha 1-adrenergic receptors in rat FRTL-5 thyroid cells.

FRTL-5 rat thyroid cells grown and maintained in a medium containing 0.05 nM thyrotropin have a 10-fold higher number of alpha 1-adrenergic receptors on their cell surface than FRTL-5 cells maintained in the absence of thyrotropin in their medium. The increased number of alpha 1-adrenergic receptors, measured as increased specific [3H]prazosin binding per microgram of DNA, is not associated with any changes in Kd values for prazosin. Thyrotropin increases the number of alpha 1-adrenergic receptors by inducing their biosynthesis, as evidence by the inhibitory effects of cycloheximide or actinomycin D; the effect on biosynthesis is cAMP-mediated, since 8-bromoadenosine 3',5'-cyclic monophosphate, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine can mimic the thyrotropin effect in both extent and time course. The alpha 1-adrenergic receptors on FRTL-5 thyroid cells have been functionally linked to iodide efflux into the follicular lumen and to the iodination of thyroglobulin--i.e., to the formation of thyroid hormones; the alpha 1-adrenergic receptor signal is mediated by Ca2+ rather than by cAMP and involves arachidonic acid intermediates. The present data thus describe a unique upregulation phenomenon wherein the sequential expression of two receptors (thyrotropin and alpha 1-adrenergic) and two distinct signal systems (cAMP and Ca2+) are apparently a necessary prelude to thyroid hormone homoeostasis.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Characterization of monoclonal antibodies raised against solubilized thyrotropin receptors in a cytochemical bioassay for thyroid stimulators.

Selected clones of monoclonal antibodies from mice immunized with solubilized preparations of bovine TSH receptors have been characterized in a cytochemical bioassay (CBA) for thyroid stimulators. This assay is based upon quantification of changes in naphthylamidase activity of sections of guinea pig thyroids with use of a chromogenic substrate. Monoclonal 22A6 is a thyroid-stimulating antibody directed at a site within the TSH receptor. Thus, although it is a weak inhibitor of 125I-TSH binding to thyroid membranes, 22A6 is inhibited from binding to membranes by TSH, exhibits a more than additive agonist effect on adenylate cyclase activity when tested at low TSH concentrations in thyroid cells, and is a competitive antagonist of TSH enhancement of adenylate cyclase activity at high TSH concentrations. In the CBA, 22A6 is a stimulator whose maximal activity is obtained with 77 pg/ml (3-min exposure). Dose-response curves of a long acting thyroid stimulator (LATS)-B standard and 22A6 have slopes which are not significantly different; as anticipated, the response to LATS-B is inhibited by antihuman immunoglobulin G (IgG) and that due to 22A6 by antimouse IgG. In contrast to 22A6, monoclonal 11E8 is a relatively potent inhibitor of 125I-TSH binding as well as TSH stimulation of adenylate cyclase activity, while failing to act as a stimulator itself. 11E8 is itself inactive as a stimulator in the CBA over a wide dose range; it does, however, inhibit TSH stimulation in the CBA. This inhibition is abolished by antimouse IgG. The transient peak of response observed in time courses to TSH occurs later in the presence of 11E8. Unlike its effect on TSH 11E8 shows relatively low potency (greater than 10,000-fold lower) when inhibiting stimulation by the thyroid stimulating antibodies, 22A6 or LATS-B. Since this difference cannot be explained by quantitative differences in the ability of 22A6 or 11E8 to bind to thyroid membranes, the CBA data suggest that the stimulating antibodies, 22A6 and LATS-B, may interact with different determinants on TSH receptors then either TSH or the blocking antibody, 11E8. This also implies that in Graves' disease blocking antibodies may be incompletely expressed in the presence of stimulating antibodies, although they may be potent inhibitors of TSH binding, as measured in receptor assays.

Adenylyl Cyclases↗
PubMed1985

Expression of the microsomal antigen on the surface of continuously cultured rat thyroid cells is modulated by thyrotropin.

The thyroid microsomal antigen, commonly implicated in thyroid autoimmune diseases, is not confined to cytoplasm, but is also present on the surface of human thyroid cells in primary culture. In this study, a strain of differentiated rat thyroid cells (FRTL5) grown in continuous culture was used to investigate the relationship between functional status of the thyroid cell and expression of microsomal antigen on its surface. Sera from eight patients with Hashimoto's thyroiditis, one with idiopathic hypothyroidism, and three with hyperthyroid Graves' disease were selected for the presence of microsomal antibody, but undetectable thyroglobulin antibody. One additional serum sample from a patient with Graves' disease, which was negative for both thyroid antibodies was used. Sera from eight normal subjects were used as controls. Indirect immunofluorescence was applied to FRTL5 cells that were viable or fixed with acetone in order to expose intracellular antigens. When FRTL5 cells were cultured in Coon's medium containing TSH (300 microU/ml), positive indirect immunofluorescence surface staining was observed with sera containing microsomal antibody, but not with control sera or with the Graves' serum negative for microsomal antibody. A rough correlation was found between the intensity of the surface fluorescence and microsomal antibody titer. After acetone treatment, microsomal antibody-positive sera produced typical cytoplasmic staining. When FRTL5 cells were cultured in the absence of TSH, disappearance of the surface fluorescence and reduction of the cytoplasmic microsomal antigen occurred. Readdition of TSH progressively restored both the surface and cytoplasmic microsomal antigen. The present data indicate that the thyroid microsomal antigen is represented on the surface of FRTL5 cells, and its expression is modulated by TSH.

Animals↗
PubMed1985

Forskolin stimulation of naphthylamidase in guinea pig thyroid sections detected with a cytochemical bioassay.

Forskolin, from the roots of the Indian medicinal plant Coleus forskohlii, has recently been shown to be a potent stimulator of adenylate cyclase in many systems, including endocrine tissues such as the thyroid gland. We describe forskolin activation of beta-naphthylamidase activity in guinea pig thyroid tissue using the cytochemical bioassay (CBA) for thyroid stimulators. This CBA is the most sensitive bioassay for TSH and LATS-B currently available, being able to detect stimulation by doses as low as 10(-5) mU TSH/l and 10(-9) mU LATS-B/l. The dose-response curve to forskolin was bell-shaped (as is seen with TSH and LATS-B) with the ascending limb of the curve produced by 10(-13) M to 10(-12) M forskolin after a 3 min exposure time. Maximal stimulation was observed with 10(-12) M forskolin. However, the dose-response curve to forskolin was not parallel to that given by TSH, the slope of the ascending limb being much greater. It has been suggested that stimulation of beta-naphthylamidase activity in the CBA is via cAMP. We report that dibutyryl cAMP at doses from 10(-16) M to 10(-11) M produces a bell-shaped dose-response curve with a very broad peak response, again not parallel to that produced by TSH. Forskolin activation of beta-naphthylamidase in the CBA is unaffected by a 1:10(6) dilution of 11E8, a monoclonal antibody raised against solubilised TSH receptors, which binds to the TSH receptor and inhibits TSH stimulation. Although the precise location of forskolin action is not known, this is further evidence that forskolin acts at a post-surface receptor site.

Aminopeptidases↗
PubMed1984

Gangliosides, the thyrotropin receptor, and autoimmune thyroid disease.

The thyrotropin (TSH) receptor has been proposed to be composed of a membrane glycoprotein and a membrane ganglioside, the former important in high affinity recognition, the latter vital for message coupling to the adenylate cyclase system. The present study used two approaches, formation of antireceptor monoclonal antibodies and reconstitution, to validate the model and further examine the role of the ganglioside. Three kinds of monoclonal antireceptor antibodies are defined. One group which inhibits TSH binding and TSH functions, i.e., TSH-stimulated adenylate cyclase activity, iodide uptake, and thyroid hormone release, is shown to be directed against the glycoprotein component of the receptor. The second group includes antibodies which mimic TSH in all stimulatory actions, are competitive agonists of TSH, are equivalent to thyroid stimulating antibodies in the sera of patients with Graves' disease, and are directed against the ganglioside component of the receptor. These stimulating monoclonal antibodies are directed against a minor ganglioside membrane component which fractionates as a disialoganglioside. When this ganglioside is incorporated into 1-8 thyroid cells which have a correlated ganglioside deficiency and TSH receptor defect, reconstitution of TSH stimulated adenylate cyclase activity occurs. Whereas the first group of antibodies inhibits TSH-stimulated function, they do not inhibit the stimulatory antibodies which mimic TSH, an observation consistent with the 2 component hypothesis of the receptor model. The third group of antibodies have a mix of properties from the first two groups and suggests that the TSH receptor in situ is an actual complex of the two components or that there are common carbohydrate determinants in the functional sites of each receptor component. Implications of a TSH receptor structure in which its ganglioside and glycoprotein components are in equilibrium with pools of free components and, in turn, components important for cholera toxin, tetanus toxin and interferon receptors are discussed. In regard to the pathogenesis of Graves' disease, the data indicate that thyroid stimulating autoantibodies are autoimmune equivalents of cholera toxin with respect to the importance of ganglioside function. Since antiidiotype studies of antibodies against TSH confirm a structural relationship between receptors for thyrotropin, cholera toxin, and thyroid stimulating autoantibodies, the data establish an unequivocal role for the ganglioside in TSH receptor structure which facilitates interpretation of in vitro experiments aimed at understanding the mechanism of ganglioside-ligand interactions.

Animals↗
PubMed1984

Characterization of monoclonal antibodies derived from lymphocytes from Graves' disease patients in a cytochemical bioassay for thyroid stimulators.

Monoclonal antibodies 208F7 and 307H6, derived from Graves' lymphocytes, were previously shown to stimulate thyroid function. We characterized these antibodies in the ultrasensitive cytochemical bioassay for thyroid stimulators. Bell-shaped dose-response curves were obtained for both antibodies, confirming their actions as thyroid stimulators; 307H6 was 10(7) times more potent than 208F7, and the ascending limb of the response curve to 307H6 was not significantly different from that of a reference preparation of thyroid-stimulating antibodies, namely LATS-B. Stimulation by both 208F7 and 307H6 was inhibited by antihuman, but not antimouse, immunoglobulin. Stimulation by 208F7, but not 307H6, was inhibited by 11E8 (a monoclonal antibody raised against the TSH receptor), which is a relatively potent inhibitor of TSH, but not thyroid-stimulating antibodies. These findings together with previous observations on the interactions of 208F7 and 307H6 with thyroid cells in both the presence and absence of TSH and of 208F7 and 307H6 with solubilized thyroid membrane components are summarized in a model relating the appropriate epitopic regions of the TSH receptor.

Animals↗
PubMed1984

Forskolin perturbs cGMP as well as cAMP levels in human thyroid cells.

Forskolin, at 10(-11) M, stimulates guanylate cyclase activity in primary human thyroid cell cultures, but does not modify cAMP accumulation. At a 10-fold higher concentration it still stimulates guanylate cyclase activity and becomes an inhibitor of cAMP production. Above 10(-9) M, forskolin stimulation of cGMP decreases, while it also becomes a stimulator of cAMP production. There is an additive effect of TSH and forskolin on cAMP production at concentrations of the diterpene which are stimulatory. Concentrations of forskolin which are inhibitory for cAMP, but stimulatory for cGMP, are inhibitory for TSH stimulation of cAMP. The addition of 8-bromo-cGMP duplicates the forskolin effect at low concentrations.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Asialoagalactothyroglobulin binds to the surface of human thyroid cells at a site distinct from the 'microsomal' autoantigen.

Human thyroglobulin has been shown for the first time to bind to the surface of cultured human thyroid follicular cells. Binding was only observed with partially glycosylated asialoagalactothyroglobulin, not with the fully glycosylated iodoprotein. The binding site for asialoagalactothyroglobulin in the cell membrane is distinct from membrane associated microsomal/microvilli antigen. Since asialoagalactothyroglobulin bears the autoantigenic determinants of the parent molecule, its ability to bind to the thyroid cell surface suggests a possible role for this protein in the pathogenesis of human thyroiditis.

Antigens↗