Plasma TSH Concentrations Research Articles

Influence of pimozide on a TRH induced TSH secretion in the rat during food deprivation.

Adult Wistar rats food deprived for 3 days had lower basal levels of TSH compared to normal fed animals. An increase of these lower levels to normal values was obtained following a prolonged (injections during 3 consecutive days) or acute treatment (single injection) with pimozide (1 mg/injection). Blood samples obtained after the last or an only injection of pimozide contained profound increased prolactin levels. Prolactin increase was more than 100-fold in fed and more than 30-fold in starved rats following prolonged pimozide treatment and more than 25-fold and 10-fold following a single injection of pimozide. An injection of 250 ng of TRH increased plasma concentrations of TSH in all groups, but this increase was more pronounced in fasted rats injected with pimozide during 3 consecutive days. It is concluded that fasting results in a dopaminergic inhibition of the sensitivity of the thyrotrophs to a TRH challenge.

Effects of thymosin alpha-1 on pituitary hormone release.

The thymosins are a family of hormone-like products of epithelial cells of the thymus which are important in maintenance and function of the immune system. Thymosin fraction 5, a partially purified extract of calf thymus, can influence pituitary hormone release. We have studied the effects of thymosin alpha 1 (T alpha 1), the first peptide isolated from thymosin fraction 5, on thyrotropin (TSH), adrenocorticotropin (ACTH), prolactin (Prl) and growth hormone (GH) release. To evaluate its effect in vivo we injected the peptide into the third ventricle of conscious male rats and measured the concentration of the pituitary hormones in plasma at different times after the injection. Following third-ventricular injection of T alpha 1, there was a significant decrease in plasma TSH and ACTH concentrations in comparison with values of control groups injected with diluent. The decrease in plasma TSH was of longer duration and was obtained with a lower dose of T alpha 1 than that of ACTH. Also, a significant decrease in plasma Prl was observed, with the same dose as for TSH. On the other hand, there were no significant changes in plasma GH. To examine if there is any direct effect of T alpha 1 at the pituitary level, we incubated hemipituitaries from male rats in vitro with different concentrations of the peptide. In this system T alpha 1 evoked a dose-dependent release of TSH and ACTH, while there was no effect on the release of Prl and GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient neonatal hyperthyrotropinaemia

Of 48 consecutive newborns with elevated umbilical venous plasma thyrotropin (TSH) concentration, only two (4%) were subsequently proved to have congenital hypothyroidism, while the other 46 had transient elevation of TSH. Compared with matched controls, these 46 newborns were all delivered vaginally ( P < 0.0003) and had a longer second stage of labour ( P < 0.002), together with higher incidences of nuchal encirclement of the cord ( P < 0.05) as well as female babies ( P < 0.05). There was no difference in the incidence of antenatal complications, mean gestational age, birth weight, or birth asphyxia. There were no small-for-gestational age infants in the study group, while four were found in the controls. The results indicate that elevated umbilical cord plasma TSH concentration may represent a response to the stress of difficult or complicated delivery in the healthy appropriate- or large-for-gestational age newborn who does not have congenital hypothyroidism.

Thyroidectomy Induces Fos-like Immunoreactivity Within Thyrotropin-Releasing Hormone-Expressing Neurons Located in the Paraventricular Nucleus of the Adult Rat Hypothalamus*

Effects of thyroidectomy on Fos-like immunoreactivity (IR) in the rat brain were examined using single and double-label immunocytochemical techniques. In particular, the possibility that Fos might be involved in thyroid hormone regulation of thyrotropin releasing hormone (TRH)-containing neurons located in the parvocellular region of the paraventricular nucleus of the hypothalamus (pPVN) was examined. Adult, male, Sprague-Dawley rats were used and all animals received either surgical removal of the thyroid gland or sham surgery. Two experiments were performed. In the first experiment, animals were killed 1, 3, or 6 days after surgery and numbers of Fos-like IR cells in the parvocellular (pPVN) and magnocellular (mPVN) regions of the PVN, the anterior hypothalamic nucleus (AH), the lateral hypothalamic nucleus (LH), and the pyriform cortex were determined. In the second experiment, animals received an intracerebroventricular injection of colchicine 5 days after surgery. The next day, animals were killed and numbers of Fos-like IR cells double-labeled for either TRH, corticotropin releasing factor (CRF), or methionine-enkephalin (met-Enk) were determined. Six days after thyroidectomy there was a significant increase in the number of Fos-like IR cells detected in the pPVN. No induction in the pPVN was observed 1 and 3 days after thyroidectomy, and no effects attributable specifically to thyroidectomy (as opposed to stress) on Fos expression in the mPVN, AH, LH, or pyriform cortex were observed. In addition, a rapid, stress-related, induction of Fos-like IR was detected in the mPVN, AH, and LH and was easily distinguished from Fos expression induced in the pPVN as a function of thyroidectomy. The time course for the effect of thyroidectomy on Fos expression in the pPVN paralleled increased plasma TSH concentration. A significant correlation between numbers of Fos-like IR cells in the pPVN and plasma TSH concentration following thyroidectomy was also observed, suggesting that plasma levels of TSH correlate directly with the number of activated TRH-containing neurons located in the pPVN. Double staining for Fos and TRH, CRF, or met-Enk revealed that thyroidectomy induced Fos-like IR specifically within TRH-, but not within CRF-, or met-Enk, expressing neurons in the pPVN. Taken together, the data suggest that Fos-like IR is induced within TRH-expressing neurons in the pPVN as a consequence of decreasing levels of circulating thyroid hormone (TH). Whether this reflects a direct effect of decreasing TH on Fos expression is not yet known; however, the data are consistent with the hypothesis that Fos is involved in TH-associated regulation of TRH production and release.

Thyroid Vascular Conductance: Differential Effects of Elevated Plasma Thyrotropin (TSH) Induced by Treatment with Thioamides or TSH-Releasing Hormone*

We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250-280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3-0.9 microgram T4 plus 0.075-0.225 microgram T3/100 g.day via continuous sc infusion), or 4) TRH (9-1200 micrograms TRH/100 g.day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney, and pancreas were determined using the reference sample version of the radioactive microsphere technique. PTU treatment led to the expected hypothyroidism, increased plasma TSH concentrations (959 +/- 66 vs. 154 +/- 22 ng/dl), increased thyroid weight (9.19 +/- 0.36 vs. 4.60 +/- 0.15 mg/100 g), and increased thyroid vascular C/mass (495 +/- 51 vs. 127 +/- 20 microliters/mm Hg.g/min). PTU-treated rats receiving partial thyroid hormone replacement demonstrated a dose-related suppression of plasma TSH, thyroid weight, and thyroid vascular C. Although, TRH treatments resulted in increased plasma TSH concentrations (e.g. 1200 micrograms TRH, 706 +/- 46 ng/dl) and thyroid weight (e.g. 1200 micrograms TRH, 7.45 +/- 0.41 mg/100 g), thyroid vascular C per tissue mass was not significantly increased after any TRH treatment (e.g. 1200 micrograms TRH, 166 +/- 19 microliters/mm Hg.g/min). Thus, at similarly elevated plasma TSH concentrations, the thyroid vascular C/mass of PTU- and TRH-treated rats constituted separate populations. Both PTU- and TRH-induced thyroid growth were accompanied by similar alterations in thyroid gland morphology (i.e. increased cellular mass with little change in the total amount of colloid). To investigate the mechanisms involved, groups of rats were treated for 6 days as follows: 1) control, 2) PTU or methimazole (25 mg MMI/day, ip), 3) PTU or MMI plus thyroid hormone replacement (1.2 micrograms T4 plus 0.3 microgram T3/d.100 g), 4) TRH (12 micrograms/100 g.day), and 5) PTU or MMI, thyroid hormones, and TRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Compensatory changes in thyroid blood flow are only partially mediated by thyrotropin

It has been shown that the compensatory growth of the thyroid gland and the compensatory increase in hormone secretion that occur after hemithyroidectomy are preceded by a dramatic increase in thyroid blood flow (BF). These alterations in the thyroid remnant may be due to the concomitant increase in plasma thyrotropin (TSH) concentrations. It has been suggested, however, that the compensatory thyroid growth may also involve a neural reflex. In this study we have investigated the role of TSH in mediating the compensatory alterations in thyroid BF and mass after subtotal thyroidectomy. Male Sprague-Dawley rats were anesthetized with ether for surgical or sham hemithyroidectomy. One-half of the hemithyroidectomized rats (HTX) received no further treatment; in the other one-half of the HTX rats (Clamp), plasma TSH levels were maintained at levels comparable with those in sham-operated animals by initiating constant thyroid hormone replacement beginning at the time of hemithyroidectomy. Plasma samples for TSH, 3,5,3'-triiodothyronine, and thyroxine radioimmunoassays were obtained 2, 7, 14, and 21 days after surgery. Thyroid BF was determined at 1, 2, and 3 wk after surgery by the reference sample version of the radioactive microsphere technique (141Ce, 15 microns diameter). Plasma TSH levels and thyroid lobe weight were significantly elevated in HTX rats but not in Clamp rats. Thyroid BF was markedly increased in HTX rats. Thyroid BF was also significantly increased in Clamp rats despite the suppression of the rise in plasma TSH concentration, but this increase was less than that in HTX rats. Neither hemithyroidectomy nor Clamp treatments had any effect on arterial blood pressure or BF to other tissues (e.g., kidney).(ABSTRACT TRUNCATED AT 250 WORDS)

Dependence of body growth on thyroid activity in turtles

AbstractWe surgically thyroidectomized (Tx) or sham‐operated hatchling slider turtles—Trachemys (Pseudemys) scripta—and measured their growth (mass and carapace length) for 5 to 7 months. Autopsy at the end of the experiments revealed that up to 30% of the thyroidectomized animals had regenerated thyroid follicles (thyroids had few but enlarged follicles). Therefore, we segregated thyroidectomized turtles a posteriori into two groups: those with observable thyroid tissue at autopsy, greater than 3 ng/ml plasma thyroxine (T4), and normal plasma T4 binding capacity were designated partial Tx (PTx), and others with no observable thyroid tissue, less than 3 ng/ml plasma T4, and low plasma T4 binding capacity were designated Tx. Growth rate was significantly reduced 6–8 weeks after thyroidectomy in the Tx animals; length‐specific growth rate was affected sooner than mass‐specific growth rate. Growth of Tx animals continued to diverge from sham turtles through the end of the experiment; PTx animals did not differ from shams at any time. In a second experiment growth rate was reduced in Tx turtles maintained under both varibale (14L:10D, thermal gradient of 19 to 40°C) and constant (constant light and temperature—30°C) environmental conditions (i.e., reduced growth rate was probably not related to a thermoregulatory dysfunction). However, all animals maintained under the constant conditions stopped growing after 3 months, whereas turtles kept under varibale conditions continued to grow to the end of the experiment (4.5 months). Thyroxine (T4) replacement therapy of long‐term Tx turtles restored growth after 6 weeks.Plasma thyrotropin (TSH) was greatly elevated in Tx turtles (301 ± 48.7 ng/ml) and at low to nondetectable levels in controls (⩾ 1 ng/ml). T4 replacement therapy was effective in reducing TSH levels in Tx turtles. Plasma T4 and TSH concentrations showed the expected inverse relationship. However, although PTx animals had elevated plasma T4 levels that were in the lower range of the sham controls (PTx: 36.6 ± 8.2 vs. 112.7 ± 17.1 ng/ml in sham), their plasma TSH was also significantly elevated (36.5 ± 9.3 ng/ml vs. 0.8 ± 0.2 ng/ml in sham). These results demonstrate the requirement of an intact thyroid gland for normal growth of turtles, and provide the first direct evidence for a role for the thyroid in body growth of a reptile. They also reveal that the set‐point for the feedback between the thyroid and pituitary secretion can be altered by perturbation of thyroid activity.

Effects of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH 2) on GH, LH, prolactin, FSH, and TSH secretion in rats with and without morphine

Plasma concentrations of GH, LH, prolactin, FSH, and TSH were evaluated in adult rats after administration of Tyr-MIF-1. Male rats were killed 0, 15, 30, and 60 min after Tyr-MIF-1 (0.02, 0.2 and 2.0 mg/kg) and ovariectomized females 15 min after injection of the peptide (0.2 and 2.0 mg/kg). The effect of Tyr-MIF-1 on pituitary hormonal secretion in morphine-treated ovariectomized rats also was studied. After 15 min, Tyr-MIF-1 (0.2 mg/kg) increased plasma concentrations of LH in males (p < 0.05) and, at 2.0 mg/kg, in ovariectomized rats (p < 0.05). Tyr-MIF-1 (0.2 mg/kg) decreased plasma concentrations of GH as compared with diluent at 15 min in males (p < 0.05) but was ineffective in ovariectomized females not receiving morphine. Plasma concentrations of prolactin, FSH, and TSH remained unchanged both in males and in ovariectomized females by any of the administered doses of the peptide at any of the times tested. When administered to ovariectomized rats injected earlier with morphine sulfate, Tyr-MIF-1 (0.2 and 2.0 mg/kg) reduced (p < 0.05) the effect of morphine (5 mg/kg) on GH secretion and tended (p = 0.061) to partially inhibit the effect of morphine (10 mg/kg) on prolactin secretion at a dose of 2.0 mg/kg. The decrease in plasma concentrations of TSH after morphine at a dose of 10 mg/kg (p < 0.001) remained unaffected by any of administered doses of Tyr-MIF-1. The results suggest that Tyr-MIF-1 may affect the regulation of the secretion of some anterior pituitary hormones.

Erythrocyte Carbonic Anhydrase I Concentration in Patients Receiving Thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.

The age at onset of diabetes influences functional and structural changes in the pituitary-thyroid axis of streptozocin-diabetic male rats

Severe structural changes leading to marked alterations in secretory activity are known to occur in the pituitary-thyroid axis 1 month after induction of postpuberal streptozocin (SZ)-diabetes. However, SZ-diabetic rats of different age groups have not been compared, nor has the maturity of the pituitary and thyroid glands at the onset of diabetes been correlated with the type and evolution of functional and structural changes. We thus induced diabetes in 1-month (prepuberal of 3-month (postpuberal) old male rats and compared diabetic with control groups 4 and 8 months after SZ or saline injection. We determined: 1) pituitary and thyroid weights, 2) the basal plasma TSH, T3, and T4 concentrations, and 3) several morphometrical measurements in the pituitary and thyroid glands. After 4 months, 1) the pituitary and thyroid weights were decreased, 2) plasma TSH and T3 were unchanged, plasma T4 was reduced. and 3) the number of thyrotropes, degenerative changes of follicle cells, and colloid area were increased, the follicle cell height as well as the number of fused cold follicles decreased, and the follicle area was unchanged in diabetic compared with control rats. The lesions were more conspicuous in pre- than in postpuberal diabetic animals. After 8 months, plasma TSH, T3, and T4 were decreased in diabetic compared with control rats. Except for the increased colloid area, all other lesions were similar, though more severe in prepuberal diabetic rats after 8 than 4 months. Few changes were found in postpuberal diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Galaninergic Mechanisms Are Involved in the Regulation of Corticotropin and Thyrotropin Secretion in the Rat*

Galanin (GAL), a 29-amino acid peptide, affects the secretion of several anterior pituitary hormones, including PRL and GH. Since GAL coexists with vasopressin and CRH in the hypothalamic paraventricular nucleus (PVN), we have studied the pharmacological and physiological actions of GAL on ACTH and TSH secretion in freely moving male rats. Cannulae were surgically implanted in the right atria and brain, intraventricular or adjacent to the PVN, of adult Sprague-Dawley rats. Seven days later, GAL (500 or 1000 ng) or saline was infused into the PVN, and serial blood samples were obtained 5, 10, 20, and 40 min after the infusion. Some animals were also stressed by the inhalation of ether vapors for 2 min after the PVN infusion. Basal ACTH concentrations were increased 2-fold in saline-treated rats; however, plasma ACTH levels were unchanged after GAL infusion. The exposure of rats to ether vapors for 2 min after the infusion of saline into the PVN increased plasma ACTH concentrations from 22.8 +/- 6.0 to 596.6 +/- 59.9 pg/ml 10 min later. However, the infusion of GAL into the PVN attenuated stress-induced ACTH secretion. After GAL infusion, peak ACTH levels (332.7 +/- 84.0 pg/ml) were attained 5 min after ether exposure, followed by a rapid decline at 10 min (P less than 0.001) and 20 min (P less than 0.05). Plasma TSH concentrations were unchanged by GAL or saline infusion and were not affected by ether vapor inhalation. To determine the physiological significance of GAL in the control of ACTH and TSH secretion, endogenous GAL was immunoneutralized by the infusion of 3 microliters GAL antiserum (GAL-AS) into the third cerebral ventricle 25 and 1 h before withdrawing blood samples every 15 min for 6 h. Animals treated with normal rabbit serum (NRS) served as controls. Plasma ACTH concentrations were unchanged by NRS during the 6-h period. However, infusion of GAL-AS raised plasma ACTH concentrations to over 400 pg/ml 75 min after infusion in some animals. In general, plasma ACTH concentrations were increased 4 h of the 6-h sampling period compared to levels in NRS-treated controls. In contrast, GAL-AS reduced TSH concentrations by 50% compared to control values. In contrast to these marked actions of centrally administered GAL, ACTH secretion from dispersed anterior pituitary cells in vitro was unaffected by GAL in concentrations up to 10(-6) M. Furthermore, GAL did not alter CRH (1 nM)-induced ACTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyrotropin-releasing hormone increases plasma atrial natriuretic peptide levels in human

The effect of thyrotropin-releasing hormone (TRH) on plasma atrial natriuretic peptide (ANP), TSH, prolactin, cortisol and aldosterone levels in 26 patients with normal pituitary and thyroid gland function was examined. Bolus iv injection of 200 micrograms TRH produced, between 0 and 60 min, a significant gradual rise of plasma ANP concentrations from 30.4 +/- 2.3 to 54.8 +/- 6.4 pg/ml (mean +/- SE). Plasma prolactin and TSH concentrations increased four- and six-fold of basal values with peak responses at 15 and 30 min, respectively, whereas plasma cortisol and aldosterone concentrations remained unchanged after the drug treatment. The patients had no significant changes in blood pressure or pulse rate. We conclude that there may be indirect mechanism(s) which result in increased ANP levels after TRH administration.

Evidence that bovine growth hormone treatment increases the rate of extrathyroidal 5′-monodeiodinase activity in cattle

This study examined the influence of bovine growth hormone (bGH) on liver and kidney thyroxine-5′-monodeiodinase activity (TMA) in growing beef cattle. In a preliminary trial (trial 1), tissue samples were obtained at slaughter from two placebo-injected and two bGH-injected (29.2 IU/day for 14 days before slaughter) Hereford heifers (398 kg avg slaughter wt), with one heifer on each treatment fed at either 1.0 or 2.0 times maintenance energy requirement. In a second trial, tissue and plasma samples were obtained from six placebo-injected and six bGH-injected (29.2 IU/day for 19 days) Hereford steers (331 kg avg slaughter wt) fed at 1.8 times maintenance energy requirement. In a third trial, liver tissue and plasma samples were obtained from 14 Angus × Hereford steers (270 kg avg wt) fed either an 8% protein, 1.96 Mcal-metabolizable energy/kg diet (8 steers) or a 14% protein, 2.67 Mcal-metabolizable energy/kg diet (6 steers) in association with acute administration of bGH. Half the steers in each group were given two injections per steer of either placebo or 37.8 IU bGH at 24-hr intervals and slaughtered 24 hr after the second injection. Units of tissue TMA in all trials were measured at slaughter; one unit defined as 1 ng T 3 generated/hr/mg protein during incubation with T 4 (1.3 fM). In trial 1, TMA in liver and kidney was 2.86 and 1.21 times greater, respectively, for bGH than for placebo treatments. In trial 2, units of TMA in liver homogenates were higher (P < .05) for bGH (4.14) than for placebo (2.83) treatments and higher (P < .02) in liver microsomal preparations for bGH (32.7) than for placebo (27.3) treatments. Units of TMA in kidney homogenates were also higher (P < .10) for bGH (1.48) than for placebo (.87) treatments and higher (P < .02) in kidney microsomal preparations for bGH (23.0) than for placebo (16.4) treatments. Following acute injection of bGH (trial 3), units of TMA in liver homogenates were higher (P < .01) for bGH (2.5) than for placebo (1.8) treatments. Plasma T 4 (70.0 vs 73.5 ng/ml) and T 3 (1.08 vs 1.18 ng/ml) concentrations appeared slightly higher in bGH-treated steers (trial 2) and increased by 20 and .5 ng/ml, respectively, (P < .01) within 6 to 12 h after acute injection of bGH (trial 3). Concurrently, plasma TSH concentration increased following acute GH injection (trial 3). Present data indicate that treatment of growing beef cattle with bGH increases extrathyroidal 5′-TMA as measured in vitro for liver and kidney tissue.

Decreased Nocturnal Surge of Thyrotropin in Nonthyroidal Illness*

To evaluate the regulation of TSH secretion in nonthyroidal illness (NTI) we studied the nocturnal TSH surge in 11 healthy controls and 26 NTI patients; none of the patients was on medication known to interfere with TSH secretion. The presence of a nocturnal TSH surge was defined as a mean nighttime TSH (the mean of 5 samples taken hourly from 0000-0400 h) significantly greater than the mean daytime TSH (the mean of 5 samples taken from 1500-1900 h). A nocturnal TSH surge was present in 11 of 26 NTI patients and in 11 of 11 controls (P less than 0.01). Both the absolute (0.3 +/- 0.1 vs. 1.0 +/- 0.2 mU/L; P less than 0.01) and relative (11 +/- 6% vs. 71 +/- 12%; P less than 0.001) nocturnal TSH surges were lower in NTI patients than in controls. NTI patients had lower plasma T3 (1.11 +/- 0.08 vs. 1.84 +/- 0.11 nmol/L; P less than 0.001) and higher plasma rT3 (0.81 +/- 0.24 vs. 0.23 +/- 0.01 nmol/L; P less than 0.001) concentrations than controls, but T4, FT4, and TSH values were similar in both groups. No differences were found between the 15 NTI patients without nocturnal TSH surge and the 11 patients with a nocturnal TSH surge in sex distribution, age, caloric intake, or plasma T4 and T3, but hospital mortality was slightly, although not significantly, higher in those with an absent nocturnal TSH surge. An absent nocturnal TSH surge occurred in 2 of 2 patients with a low TSH (less than 0.4 mU/L), in 11 of 20 patients with a normal TSH (0.4-4.0 mU/L), and in 2 of 4 patients with a high TSH (greater than 4.0 mU/L). Pituitary TSH responsiveness to TRH was similar in patients with or without a nocturnal TSH surge. We conclude that NTI is frequently associated with a decreased nocturnal TSH surge. This phenomenon is not related to ambient plasma T4, T3, or TSH concentrations or pituitary TSH responsiveness to TRH. A decreased nocturnal TSH surge appears to be one of the features of the sick euthyroid syndrome and is probably related to hypothalamic dysregulation.

The endocrine and metabolic response to feeding in the developing lamb

Oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate and the arterial plasma concentrations of glucose, non-esterified fatty acids, thyroxine (T4), 3,5,3'-tri-iodothyronine (T3), TSH, insulin, cortisol and GH were measured before and after feeding a formula milk diet to lambs aged 9, 21, 33 and 46 days. In all age groups, VO2, VCO2 and heart rate increased significantly following feeding and this effect was greatest at 9 days of age. Both VO2 and VCO2 before and after feeding decreased with age. Plasma concentrations of T3 before feeding did not change with age, but plasma T3 levels after feeding were significantly higher in lambs aged 9 days compared with 33 and 46 days. There was no effect of feeding on TSH or age on plasma TSH and T4 concentrations. In all age groups, glucose concentration increased after feeding and was paralleled by a rise in insulin concentration. At 9 and 21 days of age plasma glucose and insulin concentrations reached a plateau after the initial postprandial increase and together with a rise in respiratory quotient was indicative of a stimulation of carbohydrate oxidation. Plasma concentrations of GH increased after feeding at 21 days and older, when the mean growth rate was also stimulated by 75%. Basal metabolic rate and dietary-induced thermogenesis both decreased with age and, as a result, metabolism associated with an increase in GH levels after feeding became more efficient in terms of growth rate after 21 days. It is therefore concluded that there are major endocrine and cardiorespiratory changes in response to feeding of the young lamb which are important in stimulating and/or facilitating its growth and development.

In vitro accumulation of thyroid hormones by cultured rat hepatocytes and the biliary excretion of iodothyronines in rats treated with a novel histamine H 2-receptor antagonist

The administration of SK&F 93479, a novel histamine H 2 antagonist, to Wistar rats has been shown to produce thyroid lesions associated with an increased clearance of plasma thyroxine (T 4) and elevated plasma TSH concentrations. To determine if these changes were mediated via an increase in the hepatic clearance of thyroid hormones, the biliary clearance and hepatic accumulation of iodothyronines were measured in rats and cultured hepatocytes treated with SK&F 93479. Both the in vitro and in vivo results showed that treatment with SK&F 93479 caused an increased hepatic accumulation (approx. 200% of control) and biliary excretion (2–3-fold control values) of T 4 but had little or no effect on T 3 uptake. The in vitro studies showed that the treatment related increase in hepatic thyroxine accumulation was temperature and therefore probably energy dependent, while inhibition of cytochrome P-450 dependent enzyme activity did not alter the accumulation of T 4 suggesting that the parent compound and not some oxidative metabolite was responsible for the hepatic effects. Chromatographic analysis of bile from SK&F 93479 and phenobarbitone-treated rats showed that in the latter animals 81% of the T 4 was present as the glucuronide conjugate (consistent with enzyme induction) whereas in the SK&F 93479-treated rats only 25% was present as the conjugate with 75% being in the unconjugated form. These studies show that SK&F 93479 increases the hepatic accumulation and biliary clearance of T 4 by a novel mechanism not associated with liver microsomal enzyme induction.

Influence of tri-iodothyronine or lipid administration on the response of the pituitary-thyroid axis to exposure to cold in the newborn lamb

The influence of the administration of tri-iodothyronine (T3) or a solution of soya oil and egg lecithin on the response of the pituitary-thyroid axis to moderate exposure to cold (4 degrees C for 4 h) was studied in 24-h old lambs. In control lambs, plasma concentrations of TSH. T3 and total and free thyroxine (T4) rose significantly whereas plasma concentrations of reverse T3 remained unchanged during the test. In lambs injected i.v. with a small amount of T3 (1.23 nmol/kg) 30 min before the onset of exposure to cold, plasma concentrations of TSH, reverse T3 and total and free T4 did not change during the test. Administration of lipid 30 min before exposure to cold induced, as expected, a sharp rise in plasma free fatty acid (FFA) concentrations and a transient increase in free T4 concentrations. In these animals, plasma concentrations of TSH increased during the test as observed in control lambs, but plasma concentrations of T3, reverse T3 and total T4 did not show any significant change, whereas free T4 levels decreased during the first 2 h. These results strongly suggest, in contrast to previous results, that T3 exerts a negative feedback upon the hypothalamic-pituitary-thyroid axis in the newborn lamb. Moreover, it appears that a rise in plasma concentrations of FFA could affect neonatal thyroid function.

Increases in thyroid gland blood flow after hemithyroidectomy in the rat.

After subtotal thyroidectomy, the thyroid gland remnant undergoes compensatory alterations in function and morphology. Under the trophic stimulation of elevated plasma TSH concentrations, the thyroid remnant responds with an increase in hormone synthesis and secretion and, in addition, increases in mass. We have examined the alterations in thyroid blood flow which accompany increased secretion and growth after hemithyroidectomy (HTX) in male Sprague-Dawley rats (200-220 g). At various times after surgical HTX (1, 2, and 3 weeks), blood samples for the determination of plasma hormone concentrations were obtained and tissue blood flows were determined using 15 +/- 5 microns diameter 141Ce-labeled microspheres in a modification of the reference sample microsphere technique. The microspheres were injected directly into the left cardiac ventricle via a 23-gauge needle passed through the chest wall while a reference blood sample was collected. After the animals were killed, tissues were cleaned and weighed, then tissue and reference blood sample radioactivities were determined. In addition, thyroidal immunoreactive vasoactive intestinal peptide was measured after acetic acid (0.67 N) extraction. After HTX, plasma TSH concentrations were significantly elevated. The plasma concentrations of T4 and T3 fell, but by less than the expected 50%. The mass of the remaining thyroid lobe increased progressively over the 3 weeks post thyroidectomy, reaching approximately 70% of the total thyroid gland weight of sham-operated controls. Thyroid blood flow per gram of tissue was significantly elevated at all times post HTX. HTX did not induce any alterations in thyroidal immunoreactive vasoactive intestinal peptide concentration. Thus, after HTX, the well documented compensatory alterations in thyroid remnant growth and secretion were accompanied by a prompt and striking increase in thyroid blood flow.

Influence of Age on the Control of Thyrotropin Secretion by Thyrotropin-Releasing Hormone in the Male Rat

Alterations with age in the control of thyrotropin (TSH) secretion by thyrotropin-releasing hormone (TRH) were evaluated at the hypothalamic and pituitary levels in young (3-5 months) and old (22-24 months) male rats. In the hypothalamus, TRH was quantified in the median eminence and in the mediobasal hypothalamus; in the adenohypophysis the membrane receptors for TRH were evaluated as well as the accumulation of TRH in the gland. As for TSH, its concentration was determined in the anterior pituitary gland and in plasma. In the hypothalamus, the concentration of TRH did not differ between young and old rats in the whole mediobasal hypothalamus, but it was significantly less in the old rats at the level of the median eminence (29.9 +/- 2.8 vs. 52.2 +/- 4.3 ng/mg protein). In the adenohypophysis, the density of receptors for TRH was greater in the old than in the young rats (23.2 +/- 3.2 vs. 13.7 +/- 1.1 fmol MeTRH/mg gland)--with no change in the affinity constant--, and the amount of TRH detected was larger (10.8 +/- 1.8 vs. 2.8 +/- 0.6 pg/mg gland), illustrative of an age-related increase in TRH accumulation in the pituitary gland. The latter results are contrasting with the findings of unchanged pituitary and plasma concentrations of TSH as well as unmodified TSH response to TRH in old rats. The present data concerning TRH and the analogy with previous observations regarding dopamine in old rats are indicative of reduced neuronal activities with age at the hypothalamic level associated with impairments in the processing of the hypothalamic hormones at the pituitary level.

Plasma concentrations of pituitary and peripheral hormones during ranitidine treatment for two years in men with duodenal ulcer

The effects of treatment for 2 years with the histamine H2-receptor antagonist ranitidine (100 or 200 mg b.d. for 6 weeks followed by 100 or 200 mg daily) on plasma concentrations of pituitary and peripheral hormones in ten men with duodenal ulcer have been investigated. Stimulation tests with TRH 200 micrograms i.v. and LHRH 100 micrograms i.v. were performed before, during (6 and 24 months), and at least 6 months after treatment. Basal and TRH-stimulated prolactin (PRL) secretion was marginally reduced after treatment for 6 months, but not for 24 months. The LH response to LHRH was slightly increased after treatment for 6 months and 24 months and after the end of treatment. The plasma concentrations of TSH, FSH, cortisol, androgenic hormones, and thyroid hormones did not change significantly during treatment. No adverse effects were reported during the observation period. The few, minor changes in pituitary hormone concentrations were all within the reference range. They may be related to ranitidine treatment, but are more likely to be due to age-dependent alterations in hormone secretion. It is concluded that long-term treatment with ranitidine does not cause major changes in circulating hormone concentrations.