Impact of lead exposure on pituitary-thyroid axis in humans

Thyroid function tests (serum levels of thyroxine-T4, triiodothyronine-T3 and thyroid stimulating hormone-TSH) were performed in fifty-eight men (mean age: 31.7±10.6 years; mean duration of lead exposure: 156.9±122.7 months). These subjects were exposed to lead either as petrol pump workers or automobile mechanics. The mean whole blood lead (Pb-B) levels were 2.49±0.45 mole/l (51.90±9.40 g/dl) in the lead exposed workers and were approximately 5 times higher than in the control (n=35) subjects. No significant alteration was seen in their mean T3 and T4 levels as compared with the controls. Interestingly, T3 was significantly lower with the longer (210 months) exposure time in comparison with the group having shorter (29 months) exposure duration. The mean TSH levels were significantly (p<0.01) higher in workers exposed in comparison with the control group. This rise in TSH was independent of exposure time, but it was definitely associated with the Pb-B levels. The increase being more pronounced with mean Pb-B levels of 2.66±0.2 mole/l (55.4±4.25 g/dl) when compared with the group having mean levels of 1.51±0.30 mole/l (31.5±6.20 g/dl). The rise is TSH associated with Pb-B levels was only statistical valid, however, the levels fall within the normal laboratory range. We thus conclude that the Pb-B levels of 2.4 mole/l (50 g/dl) could enhance the pituitary release of TSH without having any significant alterations in the circulating levels of T3 and T4.     

The pituitary-thyroid axis in acromegaly

The pituitary-thyroid axis of 12 acromegalic patients was evaluated by measurement of the serum concentrations (total and free) of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) and thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) before and after iv stimulation with thyrotropin releasing hormone (TRH). Using an ultrasensitive method of TSH measurement (IRMA) basal serum TSH levels of the patients (0.76, 0.07-1.90 mIU/l) were found slightly, but significantly (P less than 0.01), lower than in 40 healthy controls (1.40, 0.41-2.50 mIU/l). The total T4 levels (TT4) were also reduced (84, 69-106 nmol/l vs 100, 72-156 nmol/l, P less than 0.01) and significantly correlated (P less than 0.02, R = 0.69) to the TSH response to TRH, suggesting a slight central hypothyroidism. The acromegalics had, however, normal serum levels of TT3 (1.79, 1.23-2.52 nmol/l vs 1.74, 0.78-2.84 nmol/l, P greater than 0.10), but significantly decreased levels of TrT3 (0.173, 0.077-0.430 nmol/l vs 0.368, 0.154-0.584 nmol/l, P less than 0.01) compared to the controls. The serum concentration of the free iodothyronines (FT4, FT3, FrT3) showed similar differences between acromegalics and normal controls. All the acromegalics showed a rise of serum TSH, GH and PRL after TRH. Positive correlation (P less than 0.05, R = 0.59) was found between the TSH and GH responses, but not between these two parameters and the PRL response to TRH. These findings may be explained by the existence of a central suppression of the TSH and GH secretion in acromegalic subjects, possibly exerted by somatostatin. Euthyroidism might be maintained by an increased extrathyroidal conversion of T4 to T3.     

The pineal and melatonin in the regulation of pituitary-thyroid axis

Studies of thyroid physiology in rats and hamsters support the view that the pineal gland has an anti-thyrotropic action. While chronic exposure of hamsters to short photoperiod, darkness, or blindness results in a depression of plasma thyroxin and plasma TSH, removal of the pineal gland, which synthesizes melatonin, prevents these effects. Melatonin administration, in the form of daily injections given late in the photoperiod, also results in inhibition of plasma thyroxin and plasma TSH. These anti-thyrotropic effects are similar to the anti-gonadotropic effects of melatonin. The results of a variety of experiments are consistent with the view that melatonin acts on a neuroendocrine control mechanism influencing synthesis or release of hypothalamic thyrotropin releasing hormone (TRH).     

Relationship between pituitary-thyroid axis hormones and anthropometric parameters in Czech adult population

Although the relationships between thyroid function and anthropometric parameters were studied in patients with thyroid disorders and in morbidly obese subjects, such data in normal healthy population are scarce. In our study, relationships between factors of body composition, fat distribution and age with hormones of the pituitary-thyroid axis were evaluated in a large, randomly selected sample of normal adult Czech population comprising of 1012 men and 1625 women. Our results exhibited weak, but significant relationships between body composition, body fat distribution and the parameters of pituitary-thyroid axis. Some of these associations were gender-specific. As shown by backward stepwise regression model, body fat distribution evaluated by centrality index (subscapular/triceps skinfold ratio) was negatively associated with free triiodothyronine (fT3) serum levels only in women, while a positive correlation of fT3 with BMI was specific for men. BMI was inversely related to free thyroxine (fT4) concentrations in women but not in men. The centrality index (CI) was positively related to TSH levels in both genders. The fT3/fT4 ratio, reflecting deiodinase activity, was inversely related to age and positively related to BMI in both genders, while the highly significant negative correlation between CI and fT3/fT4 ratio was specific for women.     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Unusual peaks of oxygen consumption under special alimentary conditions

Oxygen consumption (VO2), carbon dioxide production (VCO2), the resulting respiratory quotient (RQ), and motor activity were recorded simultaneously by an on-line computer every ten seconds during 16-20 hours in two decerebrate male rats. Being aphagic and adipsic the rats were fed twice daily by gastric intubation with a mixture of powdered milk plus sugar or plus sunflower oil (approx. 300 KJ daily) in 10-20 ml tap water. In all seven tests performed on these rats the recordings presented very steep reductions of RQ due every time to steep increases in VO2 without increases in VCO2. Mean number of VO2 peaks in all experiments was 12.4 +/- 1.8 (SE) with mean duration of 21.3 +/- 2.8 min. Two normal male rats were fed the same diet and on the same schedule: they presented similar VO2 peaks in 8 out of 12 experiments. Mean number was 8.7 +/- 1.0 with mean duration of 13.6 +/- 2.2 min. The VO2 peak periods never occurred in rats fed ad libitum. In the two normal rats oil ingestion produced more effect than sugar. It is suggested that the phenomenon could be due to a metabolic imbalance possibly of hepatic origin, more evident in decerebrate rats. VO2 peaks could be produced by enhanced ketogenesis, gluconeogenesis and/or extra-mitochondrial (peroxisomal, microsomal) oxidation.     

Effects of ovariectomy and chronic estradiol administration on pituitary-thyroid axis in adult rats

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary-thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T(4) levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase (p<0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p<0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p<0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p<0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p<0.05) of the serum level of T(4) were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary-thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.     

Effects of exposure of pregnant rats to TRH on development of the pituitary-thyroid axis in their progeny

TRH (10 and 1000 micrograms/kg body weight (BW] was injected ip into pregnant rats daily from day 0 to 20 of pregnancy, and the pituitary-thyroid axis of their pups (Mat-TRH rats) was examined on days 0, 4, 10, 21 and 90 after birth. The pituitary TSH content of male Mat-TRH rats was significantly lower on day 4, and higher on day 10 than that of control rats. The serum TSH was significantly higher on day 10 (except female 10 micrograms/kg group). An exaggerated TSH response to exogenous TRH (10 micrograms/kg BW; ip) was observed on day 10 (males, 1000 micrograms/kg group). The serum T4 level of female Mat-TRH rats was low on day 4 (1000 micrograms/kg group), and higher on day 10. On days 21 and 90, the levels of pituitary TSH, serum TSH and T4 in Mat-TRH rats were similar to those in controls, but the TSH response to TRH was still exaggerated (1000 micrograms/kg group). No significant difference between control and TRH-treated mothers was seen on days 10 and 90 postpartum except for a decreased pituitary TSH content on day 10 in the 1000 micrograms/kg group. It is concluded that repeated administration of TRH to pregnant rats shows an effect on the pituitary-thyroid axis function of their progeny in later life.     

The effect of benzodiazepine on the increase of oxygen consumption in cold exposed rats

1. Oxygen consumption and rectal temperature of warm and cold acclimated rats were measured after chronic and acute injections of saline or benzodiazepine (diazepam). 2. Benzodiazepine has blocked the increase in oxygen consumption of warm acclimated rats on exposure to cold. 3. After cold acclimation, the benzodiazepine did not affect the increase in oxygen consumption. 4. Benzodiazepine caused a slight hypothermia when injected chronically, but did not affect rectal temperature over a short period of time.     

The use of intramuscularly administered methyl-TRH to evaluate the pituitary-thyroid axis.

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.     

Effects of thyroxine and cold exposure on hypothalamic TRH levels in rats with various pituitary-thyroid states.

The hypothalamic content and concentration of thyrotropin-releasing hormone (TRH) were determined by radioimmunoassay in normal, thyroidectomized, hypophysectomized and cold-exposed rats with or without thyroxine. In normal animals, the single administration of thyroxine (1,5 and 20 microgram/100 g B.W.) altered neither the content nor the concentration of TRH in the hypothalamus. However, seven days' administration of this hormone resulted in the dose-dependent increase in the hypothalamic TRH levels. In thyroidectomized rats the hypothalamic TRH levels were slightly reduced in spite of the marked increase of plasma TSH levels and decrease of pituitary TSH levels. In the animals given thyroxine (10 microgram/100 g B.W.) for 7 days in addition to thyroidectomy, however, the TRH levels exceeded that in the animals which underwent throidectomy alone. The hypothalamic TRH levels were markedly reduced in hypophysectomized rats. Conversely, in hypophysectomized rats given 7 days' thyroxine (1 and 5 microgram/100 g B.W.), the levels were increased dose-dependently. In cold-exposed rats, the plasma TSH levels roughly doubled, but the TRH levels remained unchanged. These findings strongly suggest that the feedback site of thyroxine extends not only to the pituitary gland but also to the hypothalamus, and that thyroxine has an increasing effect of the hypothalamic TRH level, though the mechanism(s) remain to be clarified.