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Biomedical subjects

A S Jennings

Publications and source records attributed to A S Jennings.

At least 19 recordsLinked to original sources
PubMed1990

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on the pituitary-thyroid axis in rats.

Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid gland by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary's response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T3 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5'-deiodinase activity. These data demonstrate that dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine's effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary's TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.

Administration, Oral↗
PubMed1990

Controlled trial of the metabolic effects of a very-low-calorie diet: short- and long-term effects.

Resting energy expenditure (REE), weight, and body composition were measured up to seven times in 13 obese women during a 24-wk study. Patients were randomly assigned to a very-low-calorie diet (VLCD, 500 kcal/d) or a balanced-deficit diet (BDD, 1200 kcal/d). After 8 wk of supplemented fasting, REE of the VLCD patients decreased by 17% whereas that of the BDD patients was virtually unchanged. REE of the VLCD patients increased during 12 subsequent weeks of realimentation such that differences in REE between the two groups were not statistically significant at week 24 (VLCD = -11%, BDD = -2%). Reductions in weight and fat-free mass (FFM) were 12.1% and 3.6% for the VLCD patients and 10.6% and 4.1% for the BDD patients, respectively. There were no significant differences between the groups in pre- to posttreatment changes in REE normalized to FFM. Results suggest that REE recovers partially after consumption of a VLCD. They also provide evidence of a possible metabolic advantage of weight loss by a more moderate restriction.

Body Composition↗
PubMed1988

Vitamin D uptake and metabolism by perfused rat liver: influences of carrier proteins.

Several blood proteins have been associated with the transport of vitamin D sterols. Vitamin D is synthesized in the skin or absorbed from the intestine, and there is evidence for different rates of transfer to the liver from these sources. To evaluate the influences of various plasma proteins on the hepatic accumulation of vitamin D3, human plasma albumin, D-binding protein, chylomicrons, chylomicron remnants, low density lipoprotein (LDL) and high density lipoprotein were isolated and incubated with [3H]vitamin D3 before single-pass perfusions of the isolated, vitamin D-deficient rat liver. Hepatic uptake of sterol was greatest when vitamin D3 was presented on LDL or chylomicron remnants, whereas D-binding protein permitted the least uptake. Silicic acid chromatography revealed greater amounts of 25-hydroxyvitamin D3 when substrate was presented on carriers known to have hepatic receptors. After iv administration of tracer amounts of vitamin D3 to fasting rats, gradient gel electrophoretic analyses of plasma revealed most of the [3H] associated with the vitamin D-binding protein, and smaller amounts associated with LDL and high density lipoprotein. Our results suggest a major role for chylomicron remnants in the hepatic presentation of ingested vitamin D3 and support the possibility that hepatic delivery from cutaneous sites may involve lipoprotein carriers.

Animals↗
PubMed1985

Computed tomography findings in clinically normal and abnormal thyroid patients.

Fifty normal volunteers had unenhanced thyroid computed tomography scans. A range of normal computed tomography densities and volumes was established for each age group. Pre- and postcontrast scans were done on 47 abnormal patients with hemorrhagic cysts, multinodular goiter, thyroiditis, papillary carcinoma, and benign adenomas. The computed tomography characteristics of each of the pathologic groups was noted for both the abnormal areas and the uninvolved part of the gland. Preliminary observations of the computed tomography characteristics of each abnormality are discussed.

Adenoma↗
PubMed1985

Intrathecal triiodothyronine administration causes greater heart rate stimulation in hypothyroid rats than intravenously delivered hormone. Evidence for a central nervous system site of thyroid hormone action.

To determine whether intracerebrally localized iodothyronines produce thyroid hormone-related functional effects, heart rate responses were compared in conscious hypothyroid rats given triiodothyronine (T3) by either the intrathecal or the intravenous route. A significant increase in heart rate occurred within 18 h after 1.5 nmol T3/100 g body wt was delivered intrathecally through a cannula previously placed in the lateral cerebral ventricle. Injection of the same T3 dose intravenously through an indwelling jugular catheter or injection of vehicle only by either route produced no significant increase in heart rate during the 48-h postinjection period of observation. These differences were observed even though integrated serum T3 concentrations were significantly lower after intrathecal than after intravenous T3 injection. The results indicate that thyroid hormone effects on heart rate are exerted within the brain as well as within the heart.

Animals↗
PubMed1985

Triiodothyronine production by the perfused rat kidney is reduced by diabetes mellitus but not by fasting.

The effects of fasting and streptozotocin-induced diabetes on renal T3 production were studied in the isolated perfused rat kidney. Kidneys were perfused for 1 h at 37 C and pH 7.4 with two perfusion media, containing different oncotic agents (BSA and a modified collagen product, Haemaccel) and with widely varying free T4 concentrations [15.6 ng/dl (200 pM) in BSA, 132 ng/dl (1703 pM) in Haemaccel]. Basal kidney T3 concentrations fell by 65.3 +/- (SE) 5.2 and 56.4 +/- 3.4% of control in fasted and diabetic rats, respectively, in parallel with similar decreases in serum T3 concentrations. Fasting did not alter T3 production, T4 uptake, or the conversion of T4 to T3 in the perfused kidney. In contrast, diabetes decreased renal T3 production by 43.7 +/- 5.4% (P less than 0.001) and 31.2 +/- 3.5% (P less than 0.005) from control when perfused with BSA and Haemaccel, respectively. This decline in T3 production was the result of an insulin-reversible decrease in the conversion of T4 to T3, whereas T4 uptake was unchanged. Kidneys from diabetic rats retained more of the T3 produced than did kidneys from control rats, and this was also reversed with insulin treatment. These studies demonstrate significant differences in the metabolism of T4 and disposition of the T3 generated in the kidneys of fasting and diabetic rats. In both fasting and diabetes, T4 metabolism in the kidney was qualitatively and quantitatively different than that previously observed in the perfused liver. We postulate that decreased sensitivity or exposure to intraportal hormones and/or metabolites may explain these differences.

Animals↗
PubMed1984

Thyroid lymphoma in a patient with hyperthyroidism.

A patient presenting with hyperthyroidism had a rapidly enlarging thyroid mass that histopathologically was a diffuse histiocytic lymphoma arising in a gland with Hashimoto's thyroiditis. The concurrent development of both hyperthyroidism and lymphoma may have resulted from similar immunologic abnormalities. Appreciation of the relationship between thyroid lymphoma and Hashimoto's thyroiditis, and their presentation with either hypothyroidism or hyperthyroidism should lead to an earlier diagnosis of lymphoma and improved survival.

Body Weight↗
PubMed1984

Thyroid imaging: comparison of high-resolution real-time ultrasound and computed tomography.

High-resolution real-time ultrasound (US) and computed tomography (CT) were compared in 48 patients with a clinical diagnosis of thyroid abnormality and also correlated with biopsy or surgery. The modalities were considered comparable in 38 cases (79%), while CT was superior in 5 and US in 5. CT illustrated substernal extension of a goiter, demonstrated a 5-mm nodule not seen in US, showed 2 cases of thyroiditis better than US, and diagnosed a suspected thyroid mass as a lipoma anterior to the thyroid. US detected 4 nodules not seen on CT and resolved contiguous nodules that appeared to be a single nodule on CT. Both techniques lacked histopathological specificity. CT appears to be advantageous in detecting substernal thyroid extension and confirming thyroiditis, while the ability of US to detect small nodules makes it the procedure of choice in evaluating suspected intrinsic thyroid abnormalities.

Adolescent↗
PubMed1984

Regulation of hepatic triiodothyronine production in the streptozotocin-induced diabetic rat.

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.

Animals↗
PubMed1984

Effect of dexamethasone on triiodothyronine production in the perfused rat liver and kidney.

Dexamethasone administration to rats decreases T4-5'-deiodinase activity in liver homogenates and slices and in isolated rat renal tubules. To determine if this decreased T4-5'-deiodinase activity results in decreased T3 production, rat livers and kidneys of control and dexamethasone-treated rats were perfused with medium containing free T4 concentrations approximating euthyroid rat serum, and net T3 production was measured by RIA. Dexamethasone administration decreased body weight by 14% but did not affect liver weight, kidney weight, or serum concentrations of T4 or T3. When livers were perfused with T4 concentrations of 10 micrograms/dl (free T4 = 6.5 ng/dl), hepatic T3 production, T4 uptake, and the conversion of T4 to T3 were similar in dexamethasone-treated rats and saline-treated controls. However, when livers were perfused at a T4 concentration of 125 micrograms/dl (free T4 = 81 ng/dl), dexamethasone-treated livers produced significantly less T3 than controls because of decreased conversion of T4 to T3. Hepatic deiodination of T3 and excretion of T3 into bile were not affected by dexamethasone. Renal T3 production, T4 uptake, and conversion of T4 to T3 was likewise unaffected by dexamethasone treatment when kidneys were perfused at near-normal free T4 concentrations. These studies indicate that dexamethasone treatment does not alter T3 production in the perfused liver and kidney and underscore the importance of using free T4 concentrations approximating physiologic levels when studying regulation of T3 production in individual organs.

Animals↗
PubMed1984

Effect of hypothyroidism and hyperthyroidism on triiodothyronine production in perfused rat liver.

This study was undertaken to evaluate the effect of altered thyroid states on hepatic T3 production in a functioning intact organ system, the isolated perfused liver. Thyroidectomized rats were treated for 3-4 weeks with vehicle, T4, 1.5 micrograms/100 g-1 day-1, or T4, 20 micrograms/100 g-1 day-1, to produce hypothyroidism, euthyroidism, or hyperthyroidism. Livers were perfused for 1 h with medium containing T4, 10 micrograms/dl, and T3 production was estimated by RIA. T3 production in the hypothyroid, euthyroid, and hyperthyroid groups, respectively, was 1.61 +/- (SE) 0.50, 5.18 +/- 0.55, and 15.62 +/- 1.61 ng/g-1 liver h-1. These differences in T3 production resulted entirely from changes in percent conversion of T4 to T3 which were 0.87 +/- 0.25%, 3.21 +/- 0.38%, and 12.02 +/- 1.82% in the hypothyroid, euthyroid, and hyperthyroid groups, respectively. The measured hepatic uptake of T4 decreased slightly with T4 administration from 188 +/- 13 to 162 +/- 7 and 144 +/- 10 ng/g liver in these same groups. The changes in T3 production were not accounted for by differences in biliary excretion or deiodination of T3. These studies demonstrate a stimulatory effect of T4 on the conversion of T4 to T3 which is important to altering net hepatic T3 production.

Animals↗
PubMed1983

Iodothyronine homeostasis in rat brain during hypo- and hyperthyroidism.

Thyroid hormones are concentrated, retained, and metabolized in discrete neural systems in rat brain. To determine how iodothyronine requirements of brain compare with those of other thyroid hormone-dependent tissues, we measured effects of chronic thyroid hormone deficiency or excess on brain iodothyronine economy and particularly on the intracerebral rate of triiodothyronine formation from thyroxine. The results demonstrate that despite extremes of thyroxine availability, brain thyroxine and triiodothyronine concentrations and brain triiodothyronine production and turnover rates are kept within narrow limits. Adjustments in the activity of both brain and liver help to maintain these relatively stable conditions. Following thyroidectomy, fractional rates of triiodothyronine formation from thyroxine decrease to low levels in liver, whereas they increase markedly in brain; exactly the opposite direction of change occurs in brain and liver during hyperthyroidism. These responses suggest that brain iodothyronine homeostasis is important for the function of the whole organism. Because signs of nervous system dysfunction develop in hypothyroid and hyperthyroid individuals, it is possible that even relatively small deviations of brain iodocompound economy can produce significant changes in behavior and autonomic nervous system function.

Animals↗
PubMed1983

Regulation of conversion of thyroxine to triiodothyronine in perfused rat kidney.

The factors regulating the renal uptake of thyroxine (T4), its conversion to 3,5,3'-triiodothyronine (T3), and the urinary iodothyronine excretion were studied in the perfused rat kidney. Increasing the perfusate free T4 (FT4) concentration from 1 to 11.5 times that of euthyroid rat serum resulted in a linear increase in T4 uptake and T3 production that was not saturated at the highest dose. When FT4 concentrations were increased by decreasing the perfusate albumin concentration from 7.5 to 2.5 g/dl, T4 uptake and T3 production increased in proportion to the FT4 concentration. Propylthiouracil (PTU), a 5'-deiodinase inhibitor, decreased renal T3 production by 60.5% without affecting tissue T4 uptake. In the absence of glomerular filtration, T4 uptake and T3 production were unchanged, indicating that T4 is extracted by the contraluminal surface of the renal tubule. However, probenecid, an inhibitor of contraluminal organic acid uptake, did not decrease but increased T4 uptake and T3 production by increasing the perfusate FT4 fraction in the perfusate. There was no net renal 3,3',5'-triiodothyronine (rT3) production from T4, and degradation and urinary excretion of T3 were negligible. The urinary excretion of T4 and T3 correlated closely with the degree of proteinuria.

Animals↗
PubMed1979

Regulation of the conversion of thyroxine to triiodothyronine in the perfused rat liver.

This study was undertaken to determine what factors control the conversion of thyroxine (T(4)) to triiodothyronine (T(3)) in rat liver under conditions approximating those found in vivo. Conversion of T(4) to T(3) was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T(4) from perfusion medium and converted it to T(3). Production of T(3) by the perfused liver was a function of the size of the liver, the uptake of T(4) by the liver, and the presence of T(4)-5'-deiodinase activity. Production of T(3) was increased by increasing the uptake of T(4) by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T(4) concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T(4) to T(3). The liver had a large capacity for extracting T(4) and for T(4)-5'-deiodination to T(3), which was not saturated at a T(4) concentration of 60 mug/dl. Production of T(3) was decreased by inhibiting hepatic T(4)-5'-deiodinase with propylthiouracil, which decreased T(3) production by decreasing the conversion of T(4) to T(3). Propylthiouracil did not alter hepatic T(4) uptake. Fasting resulted in a progressive decrease in hepatic T(4) uptake to 42% of control levels by the 3rd d of fasting; this was accompanied by a proportionate decrease in T(3) production. The rate of conversion of T(4) to T(3) did not change during fasting. When T(4) uptake in 2-d-fasted rat livers was raised to levels found in fed rats by increasing the perfusate T(4) concentration from 10 to 30 mug/dl, T(3) production returned to normal. Again, no change in the rate of conversion of T(4) to T(3) was observed. These results indicate that the decreased hepatic T(3) production during fasting primarily results from decreased hepatic uptake of T(4), rather than from changes in T(4)-5'-deiodinase activity. Thus, these studies have delineated a new mechanism that functions independently of enzyme quantity or activity whereby production of T(3) from T(4) is regulated.

Animals↗