Effect of TSH and melatonin on thyroid activity in the rat.

Melatonin and TSH, injected separately, caused no change of the blood thyroxine level at 30 min after treatment. Simultaneous or subsequent administration of the two hormones induced an increase of the level. Thus, melatonin is capable of potentiating acute, thyroxine mobilizing effect of TSH.     

Role of N-terminal region of the thyrotropin (TSH) receptor in signal transduction for TSH or thyroid stimulating antibody.

To identify the site(s) on the thyrotropin (TSH) receptor that interacts with TSH or thyroid stimulating antibody (TSAb), we examined the effect of the synthetic TSH receptor peptide (termed N2 peptide, No. 35-50) on the cAMP accumulation induced by TSH or TSAb. Preincubation of bovine TSH with N2 peptide resulted in a significant and dose-dependent decrease in cAMP accumulation. This decrease was not observed when bovine TSH was preincubated with P1 peptide, which was used as a control (No. 398-417). In contrast, the N2 peptide did not affect TSAb activity in immunoglobulin fractions from three TSAb-positive patients with Graves' disease. P1 peptide also had no effect on TSAb activity. These results suggest that the N-terminal region of the TSH receptor is important for TSH action, and also that TSAb activity cannot be suppressed only by the application of the synthetic peptide corresponding to the N-terminal region.     

Effects of cold exposure or TRH on the serum TSH levels in the iron-deficient rat

Normal and iron-deficient rats were exposed to cold at 4 degrees C for 1 hr or 5 hrs and the serum TSH, T3 and T4 levels were compared with those in rats kept at room temperature (20 degrees C). There was a rise in serum TSH, T3 and T4 levels in response to 1 hr and 5 hrs of cold exposure in normal, but not in iron-deficient rats. Although pituitary TSH contents were lower in iron-deficient rats, the increases in serum levels of TSH following administration of TRH were similar in both normal and iron-deficient rats. The results suggest that the inability to respond to cold in iron-deficient rats may be due to a reduction in the release of TRH from the hypothalamus.     

Effect of methadone on TSH and thyroid hormone secretion

The hypothalamus-pituitary-thyroid function was studied in 15 male patients on chronic methadone treatment (40 mg/day). No significant variations of TSH, T4, T3 and rT3 levels were documented, either in basal conditions or after TRH stimulation; however a reduced TSH pituitary response was recorded in some patients (6 out of 15).     

Effects of acetylcholine, TSH and other stimulators on intracellular calcium concentration in dog thyroid cells

The intracellular free calcium concentration, [Ca2+]i, has been measured in dog thyroid cells using the fluorescent Ca2+-indicator, quin2. Acetylcholine or its non-hydrolyzable analog, carbamylcholine rapidly increased [Ca2+]i by 40 +/- 4% (mean +/- SE) over the basal level of 81 +/- 2 nM. This increase was totally abolished by atropine, a muscarinic cholinergic receptor blocker, but was not influenced by verapamil, a voltage dependent-calcium channel blocker. Depletion of extracellular Ca2+ by the addition of EGTA, diminished but did not abolish the response to carbamylcholine. These data suggest that cholinergic effectors increase [Ca2+]i by mobilization of Ca2+ from intracellular stores rather than from an influx of Ca2+. Addition of TSH, isoproterenol, phorbol ester, dibutyryl cyclic GMP or cyclic AMP did not elicit any change in [Ca2+]i suggesting that their action may not involve any mobilization of intracellular Ca2+. These data provide direct evidence that in the thyroid cell, cholinergic agents act via their receptors to cause a rapid increase in [Ca2+]i, which may mediate their metabolic effects.     

Effects of endogenous and exogenous opioids on splenic natural killer cell activity

Previous work from our own and other laboratories has shown that electroshock-induced neurohormonal changes in rodents could modify host-tumor interactions by both increasing the frequency and growth rate of transplanted tumors and decreasing the elimination rate of a radiolabelled natural killer (NK) cell sensitive tumor. To test whether such neurohormonal changes could affect NK activity we subjected mice to tail electrode shock (TES) and examined in vitro splenic NK activity. We found that between 30 and 60 min after TES there is a significant but transient suppression of their splenic NK activity. To determine whether TES-induced endogenous opioids might be involved in this suppression mice were given intraperitoneal injections of the opioid antagonists naloxone or naltrexone before or at the end of the TES session. These drugs prevented NK suppression. In a further test of the hypothesis that opioids alter NK activity mice were given a single intraperitoneal injection of morphine or [D-Ala2-Met5]-beta-endorphin, a relatively stable analogue of beta-endorphin, an endogenous opioid. Contrary to expectations these opioids enhanced splenic NK activity. Our interpretation of these results is that shock-induced NK suppression may not be mediated by endogenous opioids and that the effects of naloxone and naltrexone on NK activity may not be related to their opioid antagonist properties. On the contrary, opioids may participate in a homeostatic rebound from suppression mediated by other neurohormonal mechanisms activated during TES.     

Chronic effect of TSH on human thyroid tissue in organ culture

The chronic effect of TSH on thyroidal cAMP concentrations and release of thyroid hormones was investigated using human thyroid tissue in organ culture. Normal human thyroid slices were placed in HAM's F-10 synthetic culture medium in Falcon organ tissue culture dishes, and incubated at 37 degrees in a humidified atmosphere of 5% CO2 in air. Medium was changed everyday and daily T3 or T4 release was determined using concentration of T3 or T4 in the medium. After incubation, slices were transferred to the medium containing 10 mM theophylline and incubated without TSH for an additional 30 min to determine thyroidal cAMP concentrations. Thyroidal cAMP concentrations in slices incubated with 10 mU/ml of TSH increased significantly at 2, 6, and 24 hr and even on the 6th day of incubation. Daily T3 release was significantly increased above control from the 3rd day and daily T4 release from the 4th day to the 11th day of incubation with 10 mU/ml of TSH. Histologically, almost all follicles were structurally maintained even on the 11th day of incubation. These results suggest that both thyroidal cAMP concentrations and release of thyroid hormones are stimulated chronically by TSH. This organ culture system is useful for investigating chronic effects of various materials on human thyroid tissue.     

Effects of ketoacidosis and puberty on basal and TRH-stimulated thyroid hormones and TSH in children with diabetes mellitus

Basal and TRH-stimulated thyroid hormones and TSH were evaluated in two groups of prepubertal and pubertal diabetics: group B - 45 children without ketoacidosis; group C - 16 children with ketoacidosis. The diabetic patients showed no signs of diabetic microangiopathy. Fifty-three healthy subjects served as controls (group A). T4, T3, FT4 and FT3 serum levels were reduced in diabetics, particularly in ketotic ones; T4 and T3 values were lower in pubertal than in prepubertal non-ketotic diabetics and in pubertal than in prepubertal controls, while no significant difference was observed between pubertal and prepubertal ketotic patients. Moreover, no difference in rT3 serum concentrations was found between group A, B and C, but non-ketotic and ketotic pubertals showed a significant rT3 reduction if compared with non-ketotic and ketotic prepubertals and with healthy pubertals. TBG was lower in group B and group C diabetics than in controls. After TRH stimulus, T3 levels showed a significant increase both in controls and in non-ketotic diabetics, while no variation was observed in ketotic children; furthermore, at 120 minutes T3 values were lower in diabetic than in healthy children, particularly in ketotic ones. Basal TSH serum concentrations were reduced in ketotic diabetics, while no difference was found between nonketotic and control subjects. After TRH stimulus, TSH peak was higher in pubertal non-ketotic diabetics than in pubertal controls, while no difference was found between prepubertal and pubertal diabetics, both in non-ketotic and in ketotic status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of thyroidectomy and administration of propylthiouracil (PTU) or thyrotropin (TSH) to pregnant rats on the functional development of the fetal thyroid gland an immunohistochemical study

In order to elucidate the maternal factors influencing the functional development of the fetal rat thyroid gland, pregnant rats were subjected to either thyroidectomy or administration of PTU or TSH and the thyroid glands of the fetuses were examined chronologically by immunohistochemistry to detect thyroglobulin (Tg), T4 and T3. In the group undergoing thyroidectomy, the occurrence of immunoreactive Tg, T4 and T3 was the same as in the control group in spite of slight retardation of the development of the thyroid gland. On the other hand, PTU administration caused remarkable degeneration of the hyperplastic epithelium of the follicles, where immunoreactivity of T4 and T3 was barely detectable, suggesting a transplacental effect of PTU on the fetal thyroid gland. However, Tg remained unaffected and was stained as well as in the controls. Injection of TSH led to a delay in the occurrence of T4 and T3 by one day, probably due to increased levels of thyroid hormone from the stimulated thyroid gland of the mother rats.     

Effects of terrestrial buffer zones on amphibians on golf courses

A major cause of amphibian declines worldwide is habitat destruction or alteration. Public green spaces, such as golf courses and parks, could serve as safe havens to curb the effects of habitat loss if managed in ways to bolster local amphibian communities. We reared larval Blanchard's cricket frogs (Acris blanchardi) and green frogs (Rana clamitans) in golf course ponds with and without 1 m terrestrial buffer zones, and released marked cricket frog metamorphs at the golf course ponds they were reared in. Larval survival of both species was affected by the presence of a buffer zone, with increased survival for cricket frogs and decreased survival for green frogs when reared in ponds with buffer zones. No marked cricket frog juveniles were recovered at any golf course pond in the following year, suggesting that most animals died or migrated. In a separate study, we released cricket frogs in a terrestrial pen and allowed them to choose between mown and unmown grass. Cricket frogs had a greater probability of using unmown versus mown grass. Our results suggest that incorporating buffer zones around ponds can offer suitable habitat for some amphibian species and can improve the quality of the aquatic environment for some sensitive local amphibians.     

Reparative growth in the rat thyroid: effect of TSH suppression

Previous investigations have shown that thyroid incision leads to a dramatic burst of follicular cell mitotic activity in cells adjacent to the wound edge in both normal rats and rats made hypothyroid by chronic goitrogen administration. Wound-induced thyroid mitotic activity therefore, is seen in rats with either normal or supranormal levels of circulating thyrotropin (TSH). This study was designed to investigate the thyroid mitotic response to wounding in the absence of detectable levels of circulating TSH. Rats were injected with large doses of L-thyroxine twice daily to render circulating TSH undetectable. Thyroids were incised and follicular cell mitotic activity, in relation to distance from the incision, determined at 24, 48 and 72 hr after incision. A mitotic response to wounding was maintained in L-thyroxine treated rats, even though circulating TSH was undetectable. The peak of activity was at 48 hr, but was only 50% of that found in the incised normal rat thyroid. The spatial distribution of the response suggests that there are two components of the wound response in the normal thyroid, one dependent on the presence of circulating TSH, the other TSH-independent. The results are discussed in relation to current understanding of cellular growth control.