Search PubMed⌕ Search

Biomedical subjects

G Burke

Publications and source records attributed to G Burke.

At least 181 records · Page 10Linked to original sources
PubMed1976

Demonstration of a thyrotropin-responsive prostaglandin E2-9-ketoreductase in bovine thyroid.

1. Prostaglandin E2-9-ketoreductase activity was demonstrated in bovine thyroid homogenates. 2. The enzyme requires reduced pyridine nucleotide and dialysis prior to assay for optimal activity. 3. The products of the reaction, NADP and prostaglandin F2alpha, inhibit enzyme activity. 4. Sigmoidal kinetics are observed when substrate concentration is plotted against enzyme velocity, indicative of an allosteric enzyme. 5. Thyrotropin increases enzyme activity in bovine thyroid slices. This increase is both hormone- and tissue-specific.

Alcohol Oxidoreductases↗
PubMed1976

Dissociation between TSH and prolactin dynamics in treated thyrotoxicosis.

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.

Adult↗
PubMed1976

Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a "short-loop" negative feedback regulating thyroid function.

Animals↗
PubMed1975

Further characterization of bovine thyroid prostaglandin synthase.

1. Prostaglandin synthase activity (EC 1.14.99.1) was demonstrated in bovine thyroid homogenates. 2. The synthase was characterized and shares many characteristics of the well-studied seminal vesicle enzyme and can be inhibited by indomethacin and eicosa-5,8,11,14-tetraynoic acid. 3. The enzyme is localized in the microsomal fraction and is probably associated with the plasma membranes. 4. Thyrotropin, but no other hormone tested, increased the activity of the enzyme when added to a microsomal fraction obtained from bovine thyroid. This effect is tissue-specific since thyrotropin has no effect on bovine seminal esicle or lung prostaglandin synthase. 5. Thyrotropin, cyclic AMP and the phosphodiesterase inhibitors, theophylline and quazodine increase enzyme activity when preincubated with bovine thyroid slices. 6. EDTA, when included in the pre-incubation mixture, enhances the thyrotropin effect on the enzyme but not the cyclic AMP, theophylline, or quazodine augmentation of enzyme activity in bovine thyroid slices. This suggests that phospholipase A is involved in the thyrotropin stimulation of prostaglandin formation.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1975

The clinical utility of a heterologous radioimmunoassay for human prolactin.

A specific and sensitive double antibody radioimmunoassay for human prolactin has been developed utilizing anti-human prolactin and purified ovine prolactin for radioiodination. Employing this radioimmunoassay, as little as 1.5 ng of prolactin can be quantified in a ml of human serum. The prolactin in serum detected by the radioimmunoassay behaved in a similar manner to purified human 125-I-labled prolactin on polyacrylamide gel electrophoresis. Exogenous prolactin could be completely recovered when varying amounts were added to a constant volume of serum. In normal control and primary hypothyroid subjects, intravenous administration of thyrotropin-releasing hormone elicited a peak prolactin response 30 min post-injection. Hyperthyroid and hypopituitary subjects did not manifest a significant increase in serum prolactin concentration after the injection. Subjects with functional galactorrhea had high resting prolactin levels and exhibited peak increase in serum prolactin concentration at 60 min following the administration of thyrotropin-releasing hormone.

Animals↗
PubMed1975

Insulin and proinsulin release during calcium infusion in a patient with islet-cell tumor.

The infusion of calcium results in the release of gastrin, calcitonin, and serotonin from certain nonbeta islet cell tumors of the pancreas, medullary carcinomas of the thyroid, and carcinoid tumors, respectively. In this study, intravenous infusion of either calcium chloride or calcium aluconate in a patient with an islet-cell carcinoma resulted in a simultaneous rise in plasma immunoreactive insulin and proinsulin, and concurrent hypoglycemia. After resection of the tumor, calcium infusion caused no change in these parameters. Similarly, calcium infusion caused no change in plasma insulin or glucose in normal volunteers. The response of this tumor suggests that calcium infusion may be a useful provocative test to detect insulin-secreting neoplasia. A derangement of the stimulus-secretion coupling mechanism for insulin in the tumor cells may be responsible for their abnormal sensitivity to calcium ion.

Adenoma, Islet Cell↗
PubMed1975

Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat.

We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH.

Animals↗
PubMed1975

The relationship of thyroxine turnover to other parameters of peripheral thyroid function in Graves' disease.

In 28 patients with Graves' disease showing a wide range of thyroid function between the extremes of hypothyroidism and hyperthyroidism, the following parameters of peripheral thyroid function were measured: serum thyroxine concentration, serum-free thyroxine concentration, serum triiodothyronine concentration, and serum-free triiodothyronine concentration. In 25 patients, thyroxine turnover was also measured. Thyroxine turnover was found to be highly correlated with serum-free thyroxine concentration (r equals 0.9405) and serum-free triiodothyronine concentration (r equals 0.9184). Serum-free thyroxine fraction correlated with serum-free triiodothyronine fraction (r equals 0.8445), suggesting that similar factors in serum controlled the intensity of protein binding for both thyroxine and triiodothyronine. Thyroxine turnover calculated by a noncompartmental method agreed closely with values calculated by the compartmental method, suggesting that the former simpler method has general utility.

Adult↗
PubMed1973

Thyrotropin and cyclic nucleotide effects on prostaglandin levels in isolated thyroid cells.

Thyrotropin increases prostaglandin levels in isolated thyroid cells. Since comparable results were obtained with butyrated cyclic adenosine monophosphate derivatives as well as with the phosphodiesterase inhibitors quazodine and theophylline, it appears that cyclic adenosine monophosphate mediates this effect of thyrotropin. These observations suggest that intracellular prostaglandins play a role in modulating thyrotropin action on thyroid.

Animals↗