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Biomedical subjects

F Roelfsema

Publications and source records attributed to F Roelfsema.

At least 91 records · Page 5Linked to original sources
PubMed1985

Glucagon-stimulated plasma C-peptide and insulin levels in active and non-active acromegalics.

The glucagon-stimulated insulin and C-peptide release in patients with active acromegaly, cured acromegalic patients and healthy controls were studied. There was an elevation of the fasting insulin levels in active acromegalics and the fasting C-peptide levels in both patient groups. After i.v. injection of glucagon the insulin and C-peptide levels increased. The highest levels were recorded in active acromegalics, but cured patients also had higher levels than the control group. The insulin/C-peptide ratio was increased in active acromegalics in comparison with that found for inactive acromegalics and normal controls. In addition, the plasma half-lives (T1/2) of endogenous insulin and C-peptide were measured. It was found that the T1/2 for insulin was increased in active acromegalics only. From this study we conclude that even when the treatment of acromegaly is effective insulin and C-peptide secretion do not normalize due, probably, to increased synthesis and release upon stimulation of the pancreatic beta-cells. In active acromegaly the removal of insulin is probably also reduced.

Acromegaly↗
PubMed1985

Resynchronization patterns for urinary rhythms in rats after light-dark shifts.

Diurnal urinary rhythms during a fixed 12:12 light-dark cycle were studied in male and female rats. After a control period of 9 days the light-dark cycle was shifted either +6 or -6 h by delaying or advancing the light period, respectively. Subsequently the resynchronization process was studied for 19-21 days. In both male and female rats an asymmetry effect was present: resynchronization was more rapid after a -6-h shift than after a +6-h shift. However, female rats exhibited a rate of resynchronization slower than male rats. During the process of resynchronization a state of transient internal dissociation was found for all urinary constituents. These results probably point to different control systems rather than to different circadian pacemakers. Further analysis of the role of sex steroid hormones is required in view of the sex variations reported.

Adaptation, Physiological↗
PubMed1985

Concentrations of thyroxine and 3,5,3'-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique.

The present study was designed to assess the quantities of T4 and T3, and the source (i.e. plasma-derived vs. locally produced) of the latter iodothyronine, in various rat tissues. For this purpose, normal intact rats were brought to isotopic equilibrium by means of a continuous iv infusion of [125I]T4 and [131I]T3 for a prolonged period. At the end of the infusion period, the animals were bled and perfused. Either whole small organs or weighed portions of tissues were homogenized in saline. The iodothyronines were extracted with ethanol-ammonia and separated by TLC. The [125I]T3/[131I]T3 ratios for the tissue homogenates and plasma were determined, and the relative contribution of the T3 derived from local T4 to T3 conversion [abbreviated: Lc T3 (T4)] to the total T3 in a given tissue was calculated. The endogenous T4 and T3 levels in the various organs were computed from the known specific activities of the labeled iodothyronines. The concentration of T4 in plasma greatly exceeded that found for tissue. Among the tissues examined, the T4 concentration was highest in the liver and lowest in cerebral cortex and cerebellum. T3 (per gram) was most abundant in the kidney and anterior pituitary gland and least abundant in the testis, epididymis, and erythrocytes. In contrast to the other tissues investigated, the concentration of T3 in several regions of the brain and anterior pituitary gland either equalled or exceeded that of T4. Plasma exhibited by far the lowest T3/T4 ratio. For most of the organs investigated the contribution of Lc T3(T4) appeared to be low. On the other hand, in 15 tissues, including the central nervous system, the local production of T3 accounted for one fifth or more of the total T3 content. Although there were no regional differences between the total T3 levels in the brain, the relative contribution of Lc T3(T4) was 65% in the cerebral cortex and only 22% in the spinal cord. The variation in the source of T3 in the various parts of the central nervous system may be related to regional differences in T4 and T3 metabolism. The fact that the present study demonstrates that the relationship between circulating T3 and intracellular T3 varies from one organ to the next may be important for accurate interpretation of plasma T4 and T3 levels and for designing optimal thyroid hormone replacement therapy for patients with hypothyroidism.

Animals↗
PubMed1984

The contribution of local thyroxine monodeiodination to intracellular 3,5, 3'-triiodothyronine in several tissues of hyperthyroid rats at isotopic equilibrium.

The local conversion of T4 as a source of intracellular T3 in several organs of both hypothyroid and euthyroid rats has recently been recognized to be an important phenomenon. In the present study the source and quantity of T3 in various peripheral tissues of hyperthyroid rats were investigated. Athyreotic rats received a continuous iv infusion of 3.5 micrograms T4/100 g BW X day over a prolonged period in order to attain hyperthyroid conditions. At the same time, the animals also received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was achieved. After the animals were bled and perfused, the source and quantity of T3 in various tissue homogenates and subcellular preparations of liver, kidney, and the anterior pituitary gland were analyzed. In spite of the elevated plasma T3 and T4 levels, the concentration of T3 in the cerebral cortex and cerebellum was within the normal range. The contribution of T3 derived from local T4 to T3 conversion [Lc T3(T4)] was rather low in both parts of the brain (cerebral cortex, 26%; cerebellum, 15%) when compared with values previously determined for euthyroid rats (cerebral cortex, 67%; cerebellum, 50%). It is concluded that in the cerebral cortex and cerebellum of hyperthyroid rats normal T3 concentrations were maintained by a compensatory decrease in the degree of Lc T3(T4). Whereas previous studies revealed that Lc T3(T4) contributes significantly to the T3 in the pituitary glands of both hypothyroid and euthyroid rats, this was not the case for the hyperthyroid animals; virtually all T3 was derived from plasma. The elevated plasma T3 levels caused an increased T3 content in both the homogenate and the nuclear fraction, leading to plasma TSH levels which were below the detection limit. It was found that the T3 in muscle was derived exclusively from plasma. Both the liver and kidney showed high concentrations of T3. Whereas Lc T3(T4) was the main source of T3 in the liver, it contributed only a minor fraction of the total T3 content in the kidney. In the liver Lc T3(T4) accounted for 50-53% of the T3 content in the mitochondrial and cytosolic fractions and about 64% in the microsomal fraction. In the kidney there was a small, but significant, amount of Lc T3(T4) in these subcellular fractions. In contrast, in the hepatic nuclei only 13% of the T3 was attributable to Lc T3(T4), whereas no Lc T3(T4) could be detected in the renal nuclei.

Animals↗
PubMed1984

The influence of partial food deprivation on the quantity and source of triiodothyronine in several tissues of athyreotic thyroxine-maintained rats.

In the present study the influence of partial food deprivation (PFD) on the quantity and source of T3 [i.e. T3 derived from local T4 to T3 conversion (Lc T3 (T4] vs. plasma-derived T3] in several rat tissues was investigated. Two groups of athyroid rats on a synthetic diet received a continuous iv infusion consisting of T4 (1.0 microgram/100 g BW X day), [125I]T4, and [131I]T3 over a prolonged period. For one group of rats the daily food intake was restricted by one third to maintain constant BW during the infusion period. At isotopic equilibrium the mean plasma T3, T4, and TSH levels for control-fed rats were: 38 ng/dl, 5.1 micrograms/dl, and 470 ng/ml, respectively. The values for rats on PFD were T3: 22 ng/dl, T4: 4.8 micrograms/dl, TSH: less than 70 ng/ml. The [125I]T3 and [131I]T3 contents of whole homogenates from liver, kidney, thigh muscle, cerebral cortex, cerebellum, and anterior pituitary gland as well as the subcellular fractions from liver, kidney (nuclei, mitochondria, microsomes, and cytosol), and anterior pituitary gland (nuclei) were determined (after extraction in ethanol) by thin layer chromatography. The contribution of Lc T3(T4) and the total T3 levels in these tissue preparations could then be calculated. In the cerebral cortex, cerebellum, and anterior pituitary gland of PFD rats plasma-derived T3 as well as Lc T3(T4) was decreased. The total T3 level in the liver did not change under PFD, owing to an increase in Lc T3(T4). It is possible that the release of hepatic Lc T3(T4) into the blood stream was reduced. In neither group was there appreciable Lc T3(T4) in muscle. In contrast to the other tissues investigated, the [131I]T3 tissue-plasma ratio for muscle had increased under PFD, suggesting a higher uptake of T3. As a consequence, the T3 levels in the muscles of PFD rats did not differ from those in normally fed animals. For both groups of rats the contribution of Lc T3(T4) in hepatic nuclei was far lower than that found for the other hepatic cellular fractions. This would suggest that the hepatic nucleus preferentially takes up plasma-derived T3. In both control-fed and PFD rats the bulk of renal T3 appeared to be exchangeable with plasma T3. Hence the T3 levels in renal nuclei were reduced under PFD. The nuclear T3 levels in the anterior pituitaries from PFD rats were markedly decreased. Therefore it is likely that other factors determine TSH secretion under PFD.

Animals↗
PubMed1984

The influence of bromocriptine and transsphenoidal surgery on urinary androgen metabolite excretion in acromegaly.

The urinary excretion of the androgen metabolites aetiocholanolone (E) and androsterone (A) as well as DHEA, 11-hydroxy-androsterone and the cortisol metabolites 11-oxo-aetiocholanolone and 11-hydroxyaetiocholanolone in normoprolactinaemic and hyperprolactinaemic male and female acromegalics was studied and compared with that of appropriate control groups. In addition several plasma hormones were also measured. The growth hormone level in the patient group varied from 10-550 mU/l. The excretion of both 11-hydroxy-androsterone and DHEA was normal. The excretion of androsterone had decreased, while aetiocholanolone and cortisol metabolite excretion had increased. The ratio between aetiocholanolone and androsterone (E/A) excretion was significantly increased in all patient groups, but no correlation was found between the growth hormone level and the E/A ratio. Treatment with bromocriptine caused a decrease in the E/A ratio in patients with decreased growth hormone levels, but not in patients in whom the growth hormone level remained unchanged. After selective transsphenoidal removal of the pituitary adenoma the E/A ratio decreased significantly. The increased E/A ratio in untreated patients could not be attributed to eventual changes in plasma levels of cortisol, thyroxine, prolactin, testosterone or oestrogens. We therefore suggest that growth hormone is involved in androgen metabolism in acromegaly.

Acromegaly↗
PubMed1983

Sources and quantity of 3,5,3'-triiodothyronine in several tissues of the rat.

The local conversion of thyroxine (T4), which is an important source of intracellular 3,5,3'-triiodothyronine (T3) in several rat tissues, has been subject of recent investigations. In the present study the regulation of this phenomenon in vivo was investigated in various peripheral tissues of the rat. Intact euthyroid and radiothyroidectomized (Tx) rats received a continuous intravenous infusion of [125I]T4 and [131I]T3 until isotope equilibrium was attained. In addition to the labeled iodothyronines, Tx rats received a continuous intravenous infusion of 0.2 or 1.0 microgram carrier T4/100 g body wt per d, to create hypothyroid or slightly hypothyroid conditions, respectively. After the animals were bled and perfused the contribution of T3 derived from local conversion of T4 to T3 [Lc T3(T4)] to the total T3 in homogenates from several tissues and subcellular fractions from the liver, kidney, and anterior pituitary gland could be calculated. In all experiments T3 in muscle was derived exclusively from the plasma. In the cerebral cortex and cerebellum, however, most of the intracellular T3 was derived from the intracellular conversion of T4 to T3. It is demonstrated that for hypothyroid rats an increased relative contribution of Lc T3(T4) reduced the loss of total T3 in the brain. This phenomenon was also encountered for the anterior pituitary gland, although in this tissue the proportion of the total tissue T3, contributed by locally produced T3 was considerably lower than the values found for the cerebral cortex and cerebellum in all experiments. The present findings, regarding the source and quantity of pituitary nuclear T3 strongly suggest that both plasma T3 and T4 (through its local conversion into T3) play a role in the regulation of thyrotropin secretion. The contribution of Lc T3(T4) to the total pituitary nuclear T3 was of minor importance in euthyroid rats (approximately 20%), compared with that found for both groups in T4-supplemented athyreotic rats (approximately 40%). The total T3 concentration in the liver decreased from euthyroid to hypothyroid rats and was associated with a decrease in the tissue/plasma T3 concentration gradient. A minor proportion of hepatic T3 was contributed by Lc T3(T4), which in fact decreased significantly from the euthyroid to the hypothyroid state. In contrast to other subcellular fractions from the liver, no Lc T3(T4) could be demonstrated in the nuclear fraction. It is suggested that the liver plays an important role with respect to regulation of the circulating T3 concentration. In the kidney, a very small proportion of the total T3 was derived from locally produced T3 in all experiments (4-7%). As found in the liver, all nuclear T3 appeared to be derived from the plasma. In contrast to the liver, subcellular T3 pools in the kidney seemed to be exchangeable.

Animals↗
PubMed1983

The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3'-triiodothyronine in athyreotic thyroxine-maintained rats.

The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.

Animals↗
PubMed1983

Iodine kinetics in patients with euthyroid multinodular goitre compared with normal subjects.

In order to investigate whether patients with euthyroid multinodular goitre (EMG) lose more iodine through urinary excretion than is to be expected due to an elevated renal clearance of iodine and/or whether the iodine is handled differently in the thyroid of these patients than in that of normal subjects, the following data were obtained for 33 patients with EMG and 30 normal subjects: thyroid clearance (TC), absolute iodine uptake (AIU), renal 123I clearance (RC) and plasma inorganic iodine (PII). A significantly lower PII and a higher TC was found in the goitre patients. In the control group PII appeared to be higher and TC and RC lower in the older age group (greater than 50 years). The difference in PII and TC is most easily explained by a higher iodine uptake in the subgroup of normal subjects over 50 years of age. AIU did not differ in any of the groups. Thus, it may be concluded that an endogenous iodine deficiency due to elevated renal clearance of 123I is not a factor in sporadic goitre, at least in our patients. At the observed plasma iodine levels a significantly higher AIU was not found for goitrous patients.

Adolescent↗
PubMed1982

The influence of intravenous infusion of electrolytes on the diurnal excretory rhythms.

In freely moving rats the diurnal in electrolyte excretion was studied. Food was available during either the dark or the light period. The lights were on from 0800-2000; the dark phase extended from 2000-0800 hrs. The electrolyte excretory rhythms were studied during a control period, in which the minerals were present in the food, and during experimental periods, when successive minerals were not present in the food but were instead given by constant intravenous infusion. For both groups the excretory rhythms of K, Mg and P persisted during continuous infusion but the times of maximum and minimum excretion differed. Day-fed animals exhibited a remarkable decrease in amplitude during the mineral infusion period. In contrast, the calcium excretory pattern was only influenced by the feeding period.

Animals↗
PubMed1979

Exchange of triiodothyronine derived from thyroxine with circulating triiodothyronine as studied in the rat.

At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4-4 1/2 days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the concentration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.

Animals↗
PubMed1979

The influence of bromocriptine on serum levels of growth hormone and other pituitary hormones and its metabolic effects in active acromegaly.

The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.

Acromegaly↗