TSH Administration Research Articles

The nature of thyrotropin stimulation of thyroid function in Japanese quail: Prolonged thyrotropin exposure is necessary to increase thyroidal 125I uptake

1. 1. Single injections of thyrotropin (TSH) increase serum T 4 and thyroidal 32P uptake but not thyroidal 125I uptake regardless of dosage, exposure time or age. Chronic TSH exposure, with 3 or more days of injection, does increase thyroidal 125I uptake. 2. 2. Studies using iodine (I) supplementation indicated that the increased thyroidal radioiodine uptakes seen with chronic TSH administration were not due to an I deficiency in the thyroid resulting from high hormone release. 3. 3. Labeled and unlabeled experiments comparing the effects of single vs. multiple injections of TSH were used to describe the effects of TSH on hormone release, hormone production and thyroidal I uptake.

Thyrotropin-Releasing Hormone Metabolism and Extraction by the Perfused Guinea Pig Placenta*

This report describes the extraction of synthetic TRH and its metabolic conversion in the perfused guinea pig placenta. These studies were performed to obtain an estimate of fractional fetal TRH losses through the placenta and to determine if some of these losses are due to TRH metabolism. The in situ guinea pig placenta was perfused through an umbilical artery for 90 min, and placental effluent fractions were collected at timed intervals from the umbilical vein. Experiments were performed in which the perfusion buffer contained 0.01, 1, and 10 micrograms/ml or no synthetic TRH. Synthetic TRH was always perfused in the presence of 3H2O. In experiments in which TRH was perfused, the perfusion reservoir contents and placental effluent fractions were counted for 3H, and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro) was measured when 10 micrograms/ml TRH were perfused. When no TRH was perfused, the perfusion reservoir and placental effluent contents were processed to determine their content of TRH immunoreactivity. When synthetic TRH was perfused, steady state TRH concentrations were achieved in placental effluent fractions by 20-30 min. The single pass extraction of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/- 7.0% for 3H2O (P less than 0.001). No significant difference was detected regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A portion of the TRH that perfused the placenta was converted to deamido-TRH at all concentrations of perfused TRH. No conversion of TRH to cyclo(His-Pro) was noted when the highest concentration (10 micrograms/ml) of TRH was perfused. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a single pass. When the perfusion buffer was devoid of synthetic TRH, a small but significant increase in the content of TRH immunoreactivity was noted in the placental effluent compared to that in the perfusion reservoir. This was not large enough to affect calculations of the placental extraction of TRH. These studies, in addition to demonstrating that the placenta contains TRH deamidase activity, suggest that losses of fetal TRH through the placenta are not large. They do not support the current impression, based on the fetal TSH response to maternal TSH administration, that the placenta is freely permeable to TRH.

Effect of hypophysectomy on cyclic 3',5'-nucleotidemetabolizing enzymes in the rat thyroid gland.

Adenylate cyclase and cyclic AMP phosphodiesterase activities in the thyroid gland were significantly reduced after hypophysectomy, followed by a gradual restoration of the enzyme activities to the levels seen in sham-operated rats whereas a slight and persistent reduction was evident in guanylate cyclase and cyclic GMP phosphodiesterase activities in the same tissue. These changes in enzyme activities were restored by TSH administration but not by ACTH. The recovery of activity produced by TSH administration was inhibited by cycloheximide. Hypophysectomy, or TSH and cycloheximide administration, did not produce any significant changes in the concentrations of calmodulin, suggesting that the alteration of these enzyme activities is not induced by a decrease in the concentration of calmodulin. Since forskolin activation of adenylate cyclase did not restore the reduced activity in the hypophysectomized rat thyroid to the level found in the sham-operated control rat thyroid, we conclude that there is a reduction of the amount of enzyme after hypophysectomy rather than a change of the active site on adenylate cyclase. The spontaneous restoration of adenylate cyclase and cyclic AMP phosphodiesterase activities after hypophysectomy implies that cyclic AMP-metabolizing enzymes are responsive to an autoregulatory mechanism in thyroid follicular cells.

Characterization of thyrotropin-induced increase in iodothyronine monodeiodinating activity in mice.

To further characterize the effect of TSH administration on thyroid iodothyronine monodeiodinating activity, we have evaluated the in vitro conversion of T4 to T3 (outer ring deiodination) and T3 to 3,3'-diiodothyronine (T2; inner ring deiodination) by mouse thyroid, liver, and kidney homogenates, comparing tissues from TSH-treated mice (0.1-200 mU bovine TSH, ip, for 1-3 days) with tissues from saline-treated controls. The in vitro conversion activity was studied in the presence of 1-20 mM dithiothreitol; most of the studies were carried out at 4 mM. Studies were carried out at optimal pH 6.5 for outer ring and 7.8 for inner ring deiodination. The iodothyronine monodeiodinase in mouse thyroid is similar to the ones in liver and kidney. It is heat labile (inactivated at 56 C for 5 min), inhibited by propylthiouracil (0.2 mM) and ipodate (0.2 mM), and unaffected by methimazole (up to 20 mM), ascorbate (up to 0.1 M) or KI (up to 20 mM). The mean +/- SE baseline rates of T4 to T3 and T3 to T2 conversion were 100 +/- 6.3 and 56.5 +/- 2.9 pmol/mg thyroid protein X 30 min at 37 C, respectively. A significant increase in each conversion activity was found after TSH treatment (0.2 U, ip, daily for 3 days); T4 to T3 conversion rose to 282 +/- 15.4, and T3 to T2 increased to 153 +/- 7.4 pmol/mg thyroid protein (P less than 0.001). A 12.8% increase in thyroid weight was found in the TSH-treated group (P less than 0.03 compared with saline control group). Similar but less marked increased in monodeiodinating activities were seen in the liver. A minimal but significant increase in inner ring monodeiodination with no significant increase in T4 to T3 converting activity was found in kidney, which, in the mouse, has markedly less outer ring deiodinase than liver or thyroid. The iodothyronine monodeiodinating activities did not increase until 12 h in thyroid and 48 h in liver after the first dose of TSH. Significant increases in T4 to T3 and T3 to T2 conversion were seen with doses of TSH as low as 0.1 mU (ip, daily for 3 days), and there was a linear dose-response thereafter. The decay of the increased iodothyronine monodeiodinating activities after a single dose of TSH (0.2 U) appeared to be linear, with a decay t 1/2 of 1.3 days for T4 to T3 conversion and about 1.0 day for T3 to T2 conversion.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses to thyrotropin during development in Japanese quail.

Japanese quail, a species with a precocial pattern of development, were used as a model for studying the ontogeny of thyroid responses to TSH. Thiourea was administered to embryos early in incubation, and the effects were assessed by measuring thyroid 32P uptake, serum thyroid hormones, thyroid weights, and body weights. Thyroid stimulation after thiourea treatment indicated that maturation of thyroid-pituitary negative feedback occurs between days 9 and 10 of the 16.5-day incubation period. Since thyroid function continues to increase faster than thyroid size, hypothalamic or higher control of the pituitary appears to dominate over thyroid-pituitary feedback effects for the remainder of the embryonic period. TSH administration to embryos and chicks resulted in similar time-course and dose-response characteristics, as judged by the thyroid 32P uptake response. Single injections of TSH into 14-day-old embryos resulted in parallel increases in serum T3 and T4, with essentially no change in the T3 to T4 ratio. In contrast, the posthatching response of both 1-day-old chicks and adults to TSH involved significant increases in only T4 and resulted in decreased serum T3 to T4 ratios. Thus, there are developmental changes in the hormonal response to TSH. These results indicate that TSH effects on the embryonic thyroid cannot account for the increase in the T3 to T4 ratio during the perinatal hormone peak. Our data are consistent with the idea that T3 produced peripherally by monodeiodination of T4 accounts for the perinatal change in the thyroid hormone ratio.

The thyroid reserve in children with chronic lymphocytic thyroiditis revealed by the thyrotropin-releasing hormone and thyroid-stimulating hormone tests.

Serum thyroid hormone and TSH concentrations were measured before and after the administration of TRH (10 micrograms/kg body weight) and bovine TSH (10 IU) in 14 children with chronic lymphocytic thyroiditis. The TRH test showed that the responsiveness of TSH was positively correlated with the basal TSH (P less than 0.001) and inversely with the increase in serum thyroid hormones, for delta T3 (P less than 0.05) and for delta T4 (P less than 0.001). Overall, the patients had significantly lower mean values for basal T4, but not for T3. The TSH test revealed that the delta T3 was positively correlated with delta T4 (P less than 0.05). delta T3 after TSH administration was positively correlated with it after TRH (P less than 0.05). The patients were divided into three groups on the basis of their peak TSH values after TRH administration. In Group 1 (peak value below 40 microU/ml; N = 5); T3 increased significantly after TRH and TSH administrations (P less than 0.05 and P less than 0.025, respectively). In addition, delta T4 was significant after TSH administration. In Group 2 (peak TSH above 40 and less than 100 microU/ml; N = 6); only delta T3 after TRH was significant (P less than 0.05). In Group 3 (peak TSH above 100 microU/ml; N = 3); the response of thyroid hormones was blunted. Thus, the thyroid hormone responses to endogenous TSH coincided with that to exogenous TSH, and the exaggerated TSH response to TRH indicates decreased thyroid reserve.

Effects of anterior pituitary hormones and their releasing hormones on physiological and behavioral functions in rats

The effects of direct administration of TRH, TSH, LHRH, LH, ACTH, GH, FSH and prolactin into cerebral ventricle system on metabolic, respiratory, cardiovascular and behavioral responses were assessed in unanesthetized rats, Intraventricular administration of TRH, TSH, LHRH or LH caused hypothermia, decreased metabolism and/or cutaneous vasodilation at room temperature (22°C). Intraventricular administration of FSH, ACTH or prolactin caused hyperthermia, increased metabolism and/or cutaneous vasoconstriction. Intraventricular administration of GH caused an insignificant change in thermoregulatory responses. There was no change in respiratory evaporative heat loss in response to either of the drugs tested. In addition, intraventricular administration of TRH, LHRH or LH caused tachycardia, hypertension and a reduction in the epinephrine-induced reflex bradycardia. In contrast, intraventricular administration of prolactin caused bradycardia, hypotension and an enhancement in the epinephrine-induced reflex bradycardia in conscious rats. There was no change in cardiovascular function in response to intraventricular administration of TSH, FSH, ACTH or GH. Furthermore, following intraventricular administration of TRH, but not TSH, LHRH, LH, FSH, GH, ACTH or prolactin three main categories of behavior were provoked : activity of normal type—forward locomotion stimulation, head and body rearing; stereotype activity—increased grooming and head swaying; and abnormal type behavior—tail elevation and piloerection in rats. The data indicate that most of the anterior pituitary hormones and their releasing hormones act through a central mechanism to influence physiological and/or behavioral functions.

Immunohistochemical localization of thyroxine (T4) and triiodothyronine (T3) in the rat thyroid gland under various experimental conditions.

Detection of T4 and T3 in paraffin sections of the rat thyroid gland in various functional states was attempted by an immunoenzyme technique. Both hormones showed a similar localization, being detected mainly in the colloid in the follicular lumen, and sometimes in certain regions of the cytoplasm of the follicular epithelium. Following administration of TSH, their stainability was increased, and the localization within the cytoplasm became more remarkable. Decrease or disappearance of stainability was observed after hypophysectomy or administration of PTU. These findings support the view that the immunostainability of T4 and T3 is closely correlated with the functional state of the thyroid gland.

Effect of hypophysectomy and administration of TSH on the activity of monoamine oxidase in the thyroid gland of rats.

The thyroid monoamine oxidase (MAO) activity was measured in rats after hypophysectomy and TSH treatment to find out whether the thyroid MAO activity can be modified with TSH. Hypophysectomy decreased MAO activity in the thyroid gland of rats. The administration of TSH (2.5 U kg-1 daily for 5 days) to hypophysectomized rats increased MAO activity and fully compensated the absence of the pituitary. These data suggest that the thyroid gland MAO activity is under the regulatory influence of TSH.

Thyrotropin-mediated induction of thyroidal iodothyronine monodeiodinases in the dog.

To investigate the effect of TSH administration on thyroidal iodothyronine-deiodinating activity, in vitro conversion of T4 to T3, T3 to 3,3′-diiodothyronine (T2), and rT3 to T2 by canine thyroid, liver, and kidney homogenate was examined, comparing tissues from TSH-treated dogs (3 IU bovine TSH daily for 3 days) with tissues from sex- and weight-matched saline-treated controls. The in vitro conversion activities were studied in the presence of 4 mM dithiothreitol at pH 6.5 for outer ring (T4 to T3 and rT3 to T2) and at pH 7.8 for inner ring (T3 to T2) deiodination. Iodothyronine-monodeiodinating activity in dog thyroid is heat labile (inactivated at 56 C × 5 min) and pH dependent, inhibited by propylthiouracil (0.2 mM) and ipodate (0.2 mM), unaffected by methimazole (up to 4 mM), ascorbate (up to 0.1 M), or KI (up to 4 mM), and is localized in the microsomal fraction. TSH markedly stimulated thyroidal inner and outer ring iodothyronine-monodeiodinating activities. Baseline rates of T4 to T3, T3 to T2, an...

Thyroid hormone secretion rates: response to endogenous and exogenous TSH in man during surgery.

The thyroid hormone secretory response to TSH was studied in twenty-eight patients undergoing thyroid and parathyroid surgery. Eighteen patients received bovine or human exogenous TSH by injection into a thyroid artery, and 10 received TRH to stimulate endogenous TSH secretion. Thyroid secretion rates of T4, T3, and rT3 were determined directly from measurement of blood flow and the hormone gradient across the gland. A significant secretory response was seen for all three hormones following TSH increase. T3 secretion accelerated more rapidly than that of T4 and rT3, thus reducing the T4/T3 and rT3/T3 ratios. The T4/rT3 ratio fell during the first 30 min but then increased. The responses correlated with the area under the curve of the TSH serum concentration, and were similar after administration of bovine and human exogenous TSH, and TRH. Conclusions regarding preferential secretion ought to be made by comparing ratios of thyroid hormone secretion with those of the hormone content of the gland, but our results indicate that TSH induces preferential secretion of triiodothyronines in man.

Coupling Defect of Thyrotropin Receptor and Adenylate Cyclase in a Pseudohypoparathyroid Patient

A patient with type I pseudohypoparathyroidism was found to have mild hypothyroidism. The patient had an elevated basal TSH level and an exaggerated TSH response to TRH. There was no goiter despite increased TSH levels, and the 131I thyroidal uptake was low before and after exogenous TSH administration. These studies suggested that the patient might have partial resistance to TSH. The binding of radioiodinated TSH to thyroid membranes obtained by biopsy was next studied. The displacement of iodinated TSH by unlabeled TSH was found to be identical to that in normal control membranes. The adenylate cyclase stimulation by a supramaximal dose of TSH, however, was blunted (120.1 +/- 11.5 vs. 387.2 +/- 40.3 pmol cAMP/min/mg protein), while basal and NaF-stimulated activities were quite similar to the activities in normal membranes. These findings suggested a lack of signal transmission between the TSH receptor and the catalytic unit. Incubation of control membranes with TSH and GTP resulted in a synergistic effect on the adenylate cyclase activity. This was not found with the patient's membranes and suggested that the coupling failure was due to a defective guanine nucleotide regulatory protein. We conclude that in this case of type I pseudohypoparathyroidism, the associated mild primary hypothyroidism was due to a partial TSH refractoriness caused by a coupling defect between the TSH receptor and adenylate cyclase. This observation suggests that a common pathogenetic mechanism might underly type I pseudohypoparathyroidism and its associated hypothyroidism.

Effect of Ambient Salinity, Food-deprivation and Prolactin on the Thyroidal Response to TSH, andin vitroHepatic T4 to T3 Conversion in Yearling Coho Salmon,Oncorhynchus kisutch

This study examines the effect of food deprivation, increased ambient salinity and prolactin administration on the thyroidal response to ovine TSH, and in vitro hepatic monodeiodination of T4 to T3 in coho salmon, Oncorhynchus kisutch. Fed fish and fish food-deprived for 18 days showed similar significant increases in plasma T4 9 and 24 h after a single injection of TSH. Plasma T3 levels were also elevated in both fed and food-deprived fish 9 h after the TSH injection but plasma T3 levels in the food-deprived fish were markedly lower than in the fed salmon. The increase in T4 and T3 evident in freshwater-acclimated fish after TSH administration was not found in salmon acclimated to 65% sea water. Prolactin, given alone (either as a single injection or a series of three daily injections) had no effect on plasma T4 or T3 levels. When given together with TSH prolactin prolonged the T4 and T3 elevating effect of TSH. Food-deprived salmon had lower in vitro hepatic T4 to T3 conversion rates than fed groups but T4 to T3 conversion did not appear to be affected by increased ambient salinity, or by prolactin and/or TSH administration.

抗甲状腺剤による血液障害に関する臨床的ならびに実験的研究 第II編 抗甲状腺剤による血液障害に関する実験的研究

In this part, the author attempted experimental studies using rabbits for the purpose of investigating the pathogenesis of the blood disorders induced by anti-thyroid drugs: Rabbits were treated with TSH or thyroid powder in order to simulate the hyperthyroid conditions and treated with methimazole (MEZ). Although the TSH administration for 11 days could not cause consistent hyperthyroidism rabbits treated with thyroid powder for two weeks showed TBCindex of less than 0.5, accompanying elevation of RBC count, which was cancelled by MEZ administration. MEZ alone, too, could decrease the RBC count depending on its dosage. The increase of RBC induced by thyroid powder was abolished also by NMO (nitrogen mustard Noxide)administration for two weeks.In contrast, neutrophil count was decreased by the thyroid powder administration as well as by the MEZ treatment depending on its dosage. Administration of 2mg/kg or 20mg/kg MEZ added after thyroid powder administration intensified the neutrophil depression, while 10mg/kg of MEZ showed no additional effect. Recovery of the neutrophil count was faster in the 10mg/kg group than in the 2 mg/kg or 20 mg/kg group. Addition of NMO did not significantly affect the decrease of neutrophilic granulocyte cells induced by MEZ alone or MEZ after thyroid powder administration.There sults obtained could be summarized as follows:1) The RBC count increased in hyperthyroid rabbits, while the neutrophil count decreased.2) Administration of MEZ alone depressed both RBC and neutrophil counts.3) Concerning the RBC count, the opposing effects of thyroid hor mone and MEZ were cancelled in their combined administration. On the contrary, the neutrophil count was decreased depending on the MEZ doses or the severity of hyperthyroidism, but I could not demonstrate their synergistic effects.4) NMO adm inistration, as far as my experimental design is concerned could not intensify the neutrophil depressen.These experim ental results obtained are consistent with those obtained in hyperthyroid patients receiving anti-thyroid drugs. The reason why most of hyperthyroid patients receiving anti-thyroid drugs do not develop a clinically apparent not show neutropenia should be attributed to the opposing effects of thyroid hormone and MEZ on the thyroid function. It may be speculated that the neutropenia due to anti-thyroid drug occurs in the patients with some hereditary predisposition,1. g. bone marrow dysfunction, although, in these studies, by NMO administration could not prove the significance of such predisposition to the neutropenia.The pathogenesis of agranulocytosis still remains to be proven. However, this study should have clarified, at least to some extent, hyperthyroidism and that of anti-thyroid drug administration in the pathogenesis of the hematological disorder; in hyperthyroid patients receiving anti-thyroid drugs.

Human thyroid blood flow response to endogenous, exogenous human, and bovine thyrotrophin measured by electromagnetic flowmetry.

Human thyroid blood flow (TBF) was studied with electromagnetic flowmetry during operation. Measurements were made of the effect on TBF of injections of bovine TSH into one inferior thyroid artery in 6 patients; 6 other patients were given human TSH, and in 10 patients measurements were made both of TBF and endogenous TSH released after administration of TRH in a peripheral vein. The TBF increased after all three types of injection. The mean of the TBF maxima after bovine TSH was 2.26 +/- 0.35 (mean +/- SEM) relative to basal TBF, after human TSH 1.97 +/- 0.28, and after TRH 1.64 +/- 0.20. In the three groups combined it was 1.92 +/- 0.16. The TBF was often increased already during the first recording period 1-10 min after TSH or TRH administration. The mean TBF was approximately doubled at 30-50 min. There were considerable inter-individual variations in the latent time and maximum response of TBF, especially after human TSH, but we found no correlation between the response and the TSH serum concentration in any group. A prompt, but inter-individually varying, increase in TBF was confirmed. This increase is suggested to be secondary to an increased intrafollicular metabolic activity and not primarily regulating thyroid function.

Decreased thyroidal response to thyrotropin in diabetic mice.

The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP.

Further observations on the hormonal regulation of alpha-glycerolphosphate dehydrogenase in rat mammary gland: a possible role for prolactin and thyrotropin.

The roles of prolactin and thyrotropin (TSH) in the regulation of alpha-glycerolphosphate dehydrogenase (alpha-GPDH) activity in rat mammary gland were investigated by the administration of thyroid releasing hormone, bromocriptine, prolactin, TSH and triiodothyronine (T3). TRH administration failed to induce alterations in the glands from intact animals but stimulated the activity in castrated and adrenalectomized animals. Bromocriptine administration was without any effect in either group of animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activity, on the other hand, treatment with either TSH or T3 resulted in a highly significant increase in the activity. Combined administration of prolactin and TSH to hypophysectomized animals showed that prolactin is capable of partially inhibiting the TSH-induced increase. It is suggested that glucocorticoids exert primary control over the enzyme's activity with the pituitary hormones only playing a permissive role in its regulation.

Changes in the cyclic nucleotides (cCMP, cAMP, and cGMP) of rat thyroid induced by prolonged administration of LATS and TSH.

Abstract. It has recently been suggested that cyclic CMP (cCMP) has a physiological role in cell function. In this study, we examined the content of cCMP, cAMP & cGMP and each hydrolyzing enzyme (phosphodiesterase, (PDE)) in rat thyroid during administration of LATS and TSH for 7 days (Exp. 1), and also in the thyroid of rats given methylthiouracil (MTU) for 4 months (Exp. 2). Each cyclic nucleotide was determined by RIA, and PDE activity was determined according to Kuo's method. Exp. 1: the wet weight of thyroid in the LATS and TSH group increased 3 and 2 times respectively, from the control. Both the LATS and TSH groups showed increased plasma T4 and T3 levels. In both groups the cAMP content per wet weight of thyroid was increased slightly, but cGMP content did not change. In contrast, the cCMP content decreased markedly. Both the LATS and TSH groups showed an increase of cAMP-PDE activity in the thyroid, and no change of cGMP-PDE, while cCMP-PDE decreased markedly. In all groups levels of these 3 cyclic nucleotides and PDE activities in plasma were unaffected. Exp. 2: in the MTU group the thyroid weight increased 4.5 times over the control, and plasma T4 and T3 levels were extremely low. The cAMP content in whole thyroid gland and also per mg wet weight was increased markedly, but cGMP content did not change. cCMP content decreased significantly. The plasma cAMP level increased slightly, but the plasma cGMP and cCMP levels did not change. The increase of cAMP content and cAMP-PDE activity, and conversely the decrease of cCMP content and cCMP-PDE in the thyroid by LATS and TSH stimulation, suggest that cCMP may play a physiologically important role within the cells, similar to cAMP in the mechanism of hormone action.

Matrix-induced endochondral bone differentiation: influence of hypophysectomy, growth hormone, and thyroid-stimulating hormone.

The influence of hypophysectomy (hypox), GH, and TSH on the discrete phases of matrix-induced endochondral bone differentiation was investigated. [3H]Thymidine incorporation by proliferating mesenchymal cells on day 3 was inhibited by hypox, but was corrected by GH administration. On day 7, 35SO4 incorporation into cartilage proteoglycans was reduced by hypox, but was restored to values higher than controls by GH. Calcification of cartilage and bone was monitored by alkaline phosphatase activity. 45Ca incorporation into bone mineral, and total calcium. Alkaline phosphatase levels were maximal on day 11 in the controls and declined thereafter; however, the activity of alkaline phosphatase remained elevated in hypox recipients. Hypox reduced and delayed the rate and extent of calcification, as reflected by 45Ca incorporation and total calcium, respectively. The administration of GH and TSH alone and in combination restored 45Ca incorporation to control values in tibial metaphyses but not in the matrix-induced osteogenic plaques on day 10. These findings imply that the hormonal requirements for initiation of de novo mineralization of bone may be different from those required for the maintenance of mineralization that was initiated in early fetal life, as in the case of metaphyses. Hypox resulted in a delayed and reduced bone formation due to 1) inhibition of mesenchymal cell proliferation, 2) decreased and delayed chondrogenesis, 3) delayed and reduced vascular invasion, and 4) impaired bone formation.

The influence of thyrotropin and growth hormone on the thyroid gland in the hereditary dwarf mouse: a morphometric study.

Snell-type dwarf mice were injected with TSH, GH, or both hormones together for 6 days. GH induced an increase in body weight but not in the weight of the thyroid gland itself; on the contrary, TSH caused an increase in the weight of the thyroid but no increase in body weight. After TSH injection, the relative volume of the thyroid parenchyme was enhanced by 45% compared to that in untreated dwarf mice, and the radius of the follicles and follicular lumina increased by 50% and 48%, respectively. The major effect of TSH was an increase in cellular volume (+93%), and the mean number of cells in the average follicle was doubled, without a reduction in the number of follicles. GH had almost the same effect as TSH on the relative volume of the parenchyme and caused the radius of follicles and of the follicular lumina to increase by 61% and 69%, respectively. However, GH did not influence cellular volume. Its primary effect was to stimulate cellular division (cells were increased about 5 times in the average follicle) and to reduce the number of follicles. The nucleo-cytoplasmic ratio increased with GH but decreased with TSH. T4 serum levels increased to a much lesser extent with GH than with TSH, while normal values were obtained with both hormones together. At a morphological level, the combined administration of TSH and GH produced the same qualitative effects as separate administration, inducing an increase in cell volume and number which was less than the sum of the effects of each hormone administered separately.