Thyroid-epididymal relationship. I. Influence of hypothyroidism on epididymal lipids

The influence of thyroidectomy on the lipid composition of caput and cauda epididymides have been studied. The analysis was conducted in epididymal tissues free from fluids and sperm. A general tendency towards accumulation of epididymal lipids was observed in hypothyroid rats. Hypothyroidism also brought about a differential regional response, which may be age-related. The existence of a relationship between triacylglycerols, phospholipids and diacylglycerols has been suggested. Since immediate thyroxine replacement to thyroidectomised rats maintained epididymal lipids at control levels, it is concluded that hypothyroidism has a definite influence on the epididymal lipid composition.     

Influence of experimental hypothyroidism on the development of metastases in rats

The influence of experimental hypothyroidism induced by a synthetic antithyroid drug, methylthiouracil, upon the development of metastases was studied on male Wistar rats, inoculated intravenously with Walker 256 carcinosarcoma cells. The experimental results reveal obvious differences between the control group and the group previously treated with methylthiouracil, concerning the incidence, latent period, localization and tumor extension. Hypothyroidism promoted metastasis, increasing significantly the metastatic incidence (88% against 62% in controls), shortening the latent period and extending the localization of tumor metastases to unusual sites, such as liver and spinal column.     

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats

Aim

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T₄). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T₄ turnover.

Main methods

We compared serum T₄ turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T₃). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T₃ infusion.

Key findings

After the T₃ infusion, the turnover rate of serum T₄ in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T₃ infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T₃ infusion.

Significance

This study suggests that repression of the disappearance of serum T₄ in rats after Tx is a homeostatic response to decreased serum T₃ concentrations. Additionally, T₄ glucuronide is a storage form of T₄, but may also have biological significance. These results suggest strongly that repression of deiodination of T₄ by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism.     

Effects of streptozotocin-diabetes and l-thyroxine treatment on plasma amino acid levels in thyroidectomized rats

1) Thirty days after surgical thyroidectomy, one group of rats were made diabetic by treatment with streptozotocin and were studied for the next 14 days. These diabetic thyroidectomized animals were similar in body weight to their thyroidectomized controls but had higher plasma concentrations of most amino acids. 2) Treatment with 0.5, 1.0 or 2.0 micrograms of L-thyroxine/100 g body wt for 7 days prior to sacrifice produced no changes in either parameter in the diabetic thyroidectomized animals. On the contrary, in thyroidectomized controls, the L-thyroxine treatment was followed by a dose-dependent increment in body weight. In these animals, the administration of 0.5 microgram of L-thyroxine per day was associated with a marked rise in the plasma level of most amino acids, while only basic amino acid levels increased with 1.0 microgram, and levels decreased with 2.0 micrograms. 3) In the diabetic thyroidectomized rats treated with insulin for the last 7 days before sacrifice, body weight gain and the biphasic change of plasma amino acid levels were restored. 4) It is proposed that treatment of thyroidectomized controls with small doses of L-thyroxine accelerate protein breakdown accompanied by minor changes in amino acid utilization, while this latter effect increases with higher doses of the hormone. 5) Present results demonstrate that a certain amount of circulating insulin is required to obtain the response to exogenous thyroxine in diabetic thyroidectomized animals. Results are discussed in terms of the role of interhormone synergism as it affects normal sensitivity of the different hormones.     

Influence of high temperature on the enzyme activity of the small intestine in thyroidectomized rats]

It was revealed in acute experiments that exposure to high temperature changed the invertase, dipeptidase, lipolytic and alkaline phosphatase activity of the small intestinal mucosa in rats. The direction of these changes and their degree differed in the thyroidectomized and sham-operated animals. It is suggested that the thyroid hormones took part in the reaction of the fermentative systems of the small intestine to the action of the thermal factor.     

Activity of lipoprotein lipase in thyroidectomized rats

Total plasma postheparin lipolytic activity as well as lipoprotein lipase activity in plasma was higher after heparin injection in thyroidectomized rats than in controls. In contrast, the activity of liver lipase was lower in thyroidectomized rats. Adipose tissue from thyroidectomized rats contained more lipoprotein lipase activity than adipose tissue from controls as measured both in extracts of tissue homogenates and medium from in vitro incubations of tissue pieces. There were no differences between control and hypothyroid rats in the disappearance of intravenously injected 125I-labeled lipoprotein lipase, but when a low dose of heparin was injected before the labeled enzyme, the disappearance of 125I-labeled lipoprotein lipase was more retarded in thyroidectomized rats. The elimination of heparin itself was slightly retarded by thyroidectomy.     

Influence of androgen on the development of sexual behavior in rats : I. Time of administration and masculine copulatory responses, penile reflexes, and androgen receptors in females

The objective of the present study was to investigate the effect of the time of administration of androgen, during the neonatal period, on the development of masculine copulatory behavior in female rats. In addition, the influence of androgen, administered neonatally, on the development of penile reflexes and cytoplasmic androgen receptor levels in the hypothalamic-preoptic area (HPOA) was examined. Female rats were injected with 0.5 mg testosterone propionate (TP) at either 1, 8, or 24 hr after birth and again 24 hr after the first injection. Fifty percent of the females treated with TP at 1 and 8 hr after birth displayed the ejaculatory response when tested in adulthood. In contrast, 93 and 87.5% of oil-treated males and females, respectively, which were androgenized at 24 hr after birth exhibited this response. The results indicate that a considerable amount of masculinization occurs postnatally in the rat. However, none of the androgenized females displayed any penile reflexes even when tested following the display of an ejaculatory response. HPOA androgen receptor levels were somewhat higher in the oil-treated females than in males but were not correlated with the ability to exhibit ejaculation patterns.     

Effects of hypothyroidism and hyperthyroidism on GDP binding to brown-adipocyte mitochondria from rats.

1. Rats were made hypothyroid by giving them a low-iodine diet with propylthiouracil for 4 weeks, or were made hyperthyroid by injection with tri-iodothyronine (T3) over a 3-day period. 2. Brown adipocytes were isolated from the interscapular depots of these animals or from their euthyroid controls, followed by isolation of mitochondria from the cells. 3. Relative to cell DNA content, hypothyroidism decreased the maximum binding (Bmax.) of [3H]GDP to mitochondria by 50%. T3 treatment increased binding by 37%. 4. These findings, which are discussed in relation to previously observed changes in brown adipose tissue after alteration of thyroid status, suggest that mitochondrial uncoupling for thermogenesis is less or more effective in hypothyroidism or hyperthyroidism respectively.     

Study of the factors influencing cardiac growth. I. Comparison of cardiomegaly induced by isoproterenol in euthyroid and thyroidectomized rats

The purpose of the present work was to study the cardiac growth-stimulating effect of IPR in hypothyroid animals, in which the in vitro sensitivity of the myocardium to beta-adrenergic agonists is significantly decreased. To determine the degree of myocardial enlargement, wet and dry ventricle weight and myocardial RNA, DNA and protein were measured. IPR administered to euthyroid rats in a dosage of 5 mg/kg/day for 4 days induced cardiomegaly. In thyroidectomized rats, a consistent depression of IPR-induced cardiomegaly was observed. This phenomenon appears to be in accordance with earlier observations showing a marked decrease in maximal beta-receptor level of ventricular membranes after thyroidectomy or PTU treatment.     

Hippocampal afterdischarges in rats. I. Effects of antiepileptics

Hippocampal afterdischarges (ADs) are considered to be a model of complex partial seizures. To study the pharmacology of these ADs, stimulation electrodes were implanted into the dorsal hippocampus of 33 male Wistar rats. Stimulation (15-s series of monophasic rectangular pulses with a duration of 1 ms and frequency of 8 Hz) was applied four times with interstimulation intervals of 15 min. Drugs (carbamazepine 50 and 100 mg/kg; clonazepam 0.2 and 0.5 mg/kg; ethosuximide 125 and 250 mg/kg; phenobarbital 40 and 80 mg/kg) as well as solvent and isotonic saline were injected intraperitoneally 2 min after the cessation of the first AD. Duration of AD, of the latent period between AD and recurrent AD and duration of recurrent AD and the number of wet dog shakes were measured. ADs were markedly shortened by both doses of clonazepam and phenobarbital and by the higher dose of carbamazepine. The action of ethosuximide was negligible. Wet dog shakes were influenced in the same way as AD duration. Recurrent ADs were more sensitive to antiepileptics than ADs and wet dog shakes.     

Alterations in albumin secretion and total protein synthesis in livers of thyroidectomized rats.

Perfused rat livers and isolated rat hepatocytes exhibited a 50% decrease in the secretion of both albumin and total secretory proteins after thyroidectomy. In contrast, synthesis of non-secretory proteins was decreased by only 20% from the rates observed in liver preparations from euthyroid rats. These observations suggested a disproportionate effect of thyroidectomy on the synthesis of secretory proteins compared with non-secretory proteins. Disproportionate decreases in the synthesis of albumin in other endocrine-deficient states such as hypophysectomy and diabetes had previously been shown to be associated with decreases of similar magnitude in the relative abundance of albumin-mRNA sequences. In contrast, thyroidectomy did not affect the activity or amount of albumin mRNA in total liver poly(A)-containing RNA when assayed by cell-free translation and by hybridization with complementary DNA, respectively. Furthermore, labelling experiments in vivo demonstrated that albumin synthesis represented 12.9 +/- 0.5% and 12.4 +/- 0.4% of total protein synthesis in livers of thyroidectomized and euthyroid rats respectively. Therefore the fall in secretion of albumin and total secretory protein after thyroidectomy did not appear to be a reflection of disproportionate decreases in the synthesis of these proteins. Instead, defects in steps involved in the post-synthetic processing and secretion of albumin are suggested. A number of comparisons, including ribosome half-transit times, the size distributions of total and albumin-synthesizing polyribosomes, and the fraction of RNA present as inactive ribosomes, provided evidence that the overall decrease in protein synthesis after thyroidectomy was not due to generalized alterations in translational processes. Instead, the decrease in total protein synthesis appeared to reflect the RNA content of the liver, which fell in proportion to th decrease in protein synthesis.