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Biomedical subjects

K Westermark

Publications and source records attributed to K Westermark.

At least 37 records · Page 2Linked to original sources
PubMed1992

The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass.

Absorptiometry, Photon↗
PubMed1991

Thyrocyte migration and histiotypic follicle regeneration are promoted by epidermal growth factor in primary culture of thyroid follicles in collagen gel.

The effect of epidermal growth factor (EGF) on the morphology of porcine thyroid follicles cultured in collagen gel was studied by light and electron microscopy. Treatment with EGF (10 ng/ml) for 1-4 days induced a progressive migration of thyrocytes radiating from the mother follicles into the collagen lattice. Migrating cells were often connected with junctional complexes, thus forming small follicles containing microlumina, in which the limiting portion of the plasma membrane expressed microvilli. Autoradiography of [3H]thymidine incorporation in EGF-treated cultures showed that more than 80% of nuclei in mother follicles and migrating cells were labeled after 4 days. TSH (2 mU/ml) given simultaneously with EGF did not influence the effect of EGF on multiplication, migration, and formation of microfollicles. TSH given for 12 h after 4 days of exposure to EGF was able to induce luminal dilation of mother follicles, but caused no change in the appearance of microlumina. It is concluded that thyrocytes in collagen gel retain epithelial characteristics during prolonged stimulation with EGF, in spite of a migrating response. The whole sequence of events, starting with the intact follicle, i.e. multiplication, migration of thyrocytes, and formation of new follicles, could, thus, be visualized to occur in response to a single mitogen, EGF. EGF might be involved in the generation of new follicles in the intact gland.

Animals↗
PubMed1991

A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism.

Nucleotide sequence analysis of PCR fragments of TSH receptor cDNA synthesized from thyroid RNA of a patient with autoimmune hyperthyroidism, revealed two different sequences in the first position of codon 36. In one of the sequences, there was a C for G substitution leading to the D36----H substitution in the predicted peptide. Both variants were also found in genomic DNA of thyroid tissue. However, only the germ line sequence was found in other tissues representing all three different germ layers. The novel sequence is therefore likely to represent a somatic mutation in the thyroid tissue, of possible relevance for the pathogenesis of the patient's thyroid disorder.

Adult↗
PubMed1991

Epidermal growth factor stimulates thyroid follicle neogenesis in collagen gel culture.

The mechanism involved in the neoformation of thyroid follicles is poorly understood. In the present study, whole porcine thyroid follicles were cultured as "miniorgans", embedded within collagen gels. Incubation was performed up to 4 days with or without EGF (10 ng/ml) and TSH (2 mU/ml). A single dose of 3H-thymidine was added at the start of the experiments in some cases. Light microscopy and autoradiography was performed. EGF induced a dramatic migration of follicles cells; these were seen to back out from the mother follicle and formed microfollicles with normal polarity including microvilli at the apical border. As evident from the analysis of 3H-thymidine incorporation, most microfollicles were comprised of newly divided cells. The results infer a new mechanism for the neoformation of follicles in the thyroid.

Animals↗
PubMed1990

Baroreflex-governed sympathetic outflow to muscle vasculature is increased in hypothyroidism.

Microelectrode recording of muscle nerve sympathetic activity (MSA), which is baroreflex-governed and involved in cardiovascular homeostasis, was made in five patients with hypothyroidism and in seven patients with hyperthyroidism prior to treatment and after recovery to euthyroidism. Patients with hypothyroidism had a higher level of MSA when hypothyroid than after recovery (mean +/- SEM 39.3 +/- 7.1 and 26.8 +/- 7.9 bursts/min, respectively, P less than 0.05), whereas hyperthyroidism was not accompanied by a change in the number of sympathetic bursts/min. The response of MSA to manouvres known to influence the neural outflow via baroreceptors and other receptor inputs was not changed with altered thyroid function. The findings provide direct evidence of an increased sympathetic activity in hypothyroidism, but suggest that other physiological properties of MSA are intact in thyroid disease.

Adult↗
PubMed1990

Effects of interleukin 1 alpha on porcine thyroid follicles in suspension culture.

Interleukin 1, a product primarily of activated macrophages, was found to exert both a stimulatory and an inhibitory effect on porcine thyroid follicles in suspension cultures. A stimulatory effect on [125I] iodide incorporation into protein (iodination) was seen in cultures exposed to human recombinant interleukin 1 alpha (20 micrograms/l) for 1 h and (0.1 or 10 micrograms/l) for 18 h, whereas an inhibitory effect on iodination of interleukin 1 (10 micrograms/l) was registered after pre-incubation for 42 h and significant upon stimulation with TSH (200 mU/l). Cyclic AMP levels were stimulated in cells exposed to interleukin 1, however, significantly only after 42 h of pre-incubation, whereas TSH-stimulated cAMP response was inhibited by interleukin 1 already after 18 h of pre-incubation. The lumen of interleukin 1 incubated follicles was highly dilated and surrounded by a flattened epithelium. There were, however, no morphological signs of follicle disintegration or cellular cytotoxicity in the cultures exposed to interleukin 1. The data suggest that interleukin 1 might have a modulating role on thyroid function in autoimmune thyroid diseases associated with activation of intrathyroidal macrophages.

Animals↗
PubMed1988

Growth factors and the thyroid: effects of treatment for hyper- and hypothyroidism on serum IGF-I and urinary epidermal growth factor concentrations.

We investigated the impact of thyroid hormone levels on serum concentrations of IGF-I and urinary epidermal growth factor (EGF) in hyper- and hypothyroid patients before and during medical treatment. Serum IGF-I levels measured with radioreceptor-assay decreased in 12 hyperthyroid patients from 1.25 (1.02-1.80) to 1.02 (0.77-1.78) X 10(3) U/l (P less than 0.01), whereas a non-significant increase in 8 hypothyroid patients--from 1.14 (0.85-1.40) to 1.39 (1.08-1.80) X 10(3) U/l was recorded. Urinary EGF, measured with radioimmunoassay decreased in 10 hyperthyroid patients from 68.0 (38.0-122.9) to 40.9 (23.6-100.3) micrograms/g creatinine (P less than 0.001) and increased in 7 hypothyroid subjects from 23.8 (17.5-35.8) to 36.1 (24.7-60.1) micrograms/g creatinine (P less than 0.05). In hyperthyroidism, but not in hypothyroidism, the urinary excretion of creatinine changed significantly from 0.66 (0.26-1.21) to 1.52 (0.81-2.59) g/l (P less than 0.001) during treatment, thus affecting the EGF excretion values. However, a comparison of untreated hyperthyroid with untreated hypothyroid patients showed a highly significant difference in EGF excretion (P less than 0.001) despite a non-significant difference in creatinine excretion between the two groups. FT4 I concentrations correlated significantly (r = 0.83) (P less than 0.001) to EGF values in untreated hyper- and hypo-thyroid patients. Data from the present study thus conform with the view that the growth promoting effect of thyroid hormones involves a stimulated synthesis or release of classic growth factors.

Adult↗
PubMed1986

Location of epidermal growth factor receptors on porcine thyroid follicle cells and receptor regulation by thyrotropin.

By using a direct electron microscopic autoradiographical technique, we were able to demonstrate that the epidermal growth factor (EGF) receptor is asymmetrically located on polarized porcine thyroid follicle cells cultured on a collagen gel matrix. More than 80% of autoradiographical grains from [125I]EGF were associated with the basolateral cell surface compared to only about 2.5% at the apical cell margin. EGF stimulated growth only when the collagen gels were floating, indicating a basolateral location of functional EGF receptors. Preincubation with TSH or another stimulator of cAMP synthesis, forskolin, increased binding of [125I]EGF to the cells. Moreover, the subsequent mitogenic response to EGF was potentiated by such pretreatment. The results are in accordance with the hypothesis that TSH potentiates the response to EGF in the stimulation of thyroid growth.

Animals↗
PubMed1985

Thyrotropin modulates EGF receptor function in porcine thyroid follicle cells.

Porcine thyroid follicle cells in monolayer cultures were shown to contain one single class of high-affinity EGF receptors with Kd = 4.5 X 10(-10) M and approximately 20 000-25 000 receptors per cell. Suspension cultures of aggregated follicle cells, exposed to TSH for 3 days, showed a 3-fold increase in [125I]EGF binding. Scatchard analysis demonstrated that this was due to an increase in receptor number. Other cAMP-elevating agents (cholera toxin, dibutyryl cAMP, forskolin) induced a similar effect. In suspension cultures, preincubation with TSH or cholera toxin for 2 days reduced the subsequent [3H]thymidine incorporation. This inhibition was overcome by a low concentration of EGF (0.1 ng/ml). At higher concentrations of EGF (1-10 ng/ml) the incorporation of [3H]thymidine was potentiated 2-3-fold in cultures preexposed to TSH or cholera toxin. The results demonstrate the presence of a high-affinity EGF receptor in porcine thyroid follicle cells. Receptor expression, as well as responsiveness to the mitogenic action of EGF, is modulated in vitro by TSH, through a cAMP-dependent process.

Animals↗
PubMed1983

Epidermal growth factor modulates thyroid growth and function in culture.

The effect of epidermal growth factor (EGF) on the growth and function of porcine thyroid follicle suspension cultures was examined. When incubated with EGF (0.01-10 ng/ml), the incorporation of [3H]thymidine was markedly stimulated, with the half-maximal effect occurring at about 0.5 ng/ml. Through 6-day experiments, [3H]thymidine incorporation increased almost linearly after an initial lag phase of 1 day. Autoradiographical analysis showed that more than 50% of the nuclei were labeled after 4 days of incubation with EGF (10 ng/ml) compared to control values of 3-7% labeled nuclei. EGF was essentially as effective in serum-free medium as in medium containing 1% fetal calf serum. EGF added at the same concentrations that stimulated incorporation of [3H]thymidine was found to reduce iodide metabolism of the follicles within 30 min of addition; both TSH-stimulated efflux and organification of [125I]iodide were suppressed by the addition of EGF. Since EGF is a physiologically occurring substance, the data suggest that EGF might be a modulator of thyroid growth and function in vivo.

Animals↗