Search PubMed⌕ Search

Biomedical subjects

F Pekonen

Publications and source records attributed to F Pekonen.

69 records · Page 4Linked to original sources

Heterogeneous forms of thyroid-stimulating hormone in mouse thyrotropic tumor and serum: differences in receptor-binding and adenylate cyclase-stimulating activity.

Thyroid-stimulating hormone (TSH) in tumor and serum of mice with thyrotropic tumors was studied by radioimmunoassay (RIA), radioreceptor assay (RRA) and thyroid adenylate cyclase assay (ACA). In unfractionated samples, serum TSH displayed significantly higher ACA/RIA (0.69 +/- 0.10) and ACA/RRA ratios (0.79 +/- 0.04) than TSH in tumor extracts (0.45 +/- 0.05 and 0.31 +/- 0.01, respectively). After gel chromatography, both tumor and serum TSH activity measured in RIA and RRA eluted in broad, heterogeneous peaks with an apparent molecular weight range of 26,000 - 44,000 daltons. The ACA activity of tumor TSH eluted in 2 sharp peaks (26,000 and 44,000) while that of serum TSH eluted in 3 peaks (26,000, 33,000 and 44,000). The ACA/RIA and ACA/RRA ratios varied greatly among the chromatography fractions, the lowest ratios being detected in the tumor TSH of 33,000 daltons (0.02 for each) and the highest ratios in both tumor and serum TSH of 26,000 (ACA/RIA = 1.60 - 1.90, ACA/RRA = 1.12 - 1.20). Since previous biosynthetic studies have suggested that such heterogeneous forms of mouse tumor TSH differ solely in carbohydrate content, our data suggest that the biologic activity of TSH may be modulated by its glycosylation.

Adenylyl Cyclases↗

Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn.

Eleven pregnant women with concomitant hyperthyroidism were treated with antithyroid drugs. At monthly intervals serum thyroxine (T4) and triiodothyronine (T3) were measured with radioimmunoassay, the Sephadex uptake of radioactive triiodothyronine (T3U) determined the free T4 and T3 indices calculated (FT4I, FT3I). TSH-binding inhibiting immunoglobulins (TBII) were determined by the radiomembrane assay. Serum TSH and T4 were measured at delivery from cord blood and/or from the newborn infants some days after birth. Serum TSH was significantly elevated in one infant. There was an inadequate post-partal rise in serum T4 concentration in this child and in another who showed only a marginal elevation of TSH. The mothers of these infants were given carbimazole in doses of 30 and 25 mg/day, respectively, at the time of delivery. No significant changes were seen in other infants, the daily doses being 20 mg of carbimazole or less. There was no clinical indication of hypo- or hyperthyroidism in any of the newborn. The TBII were positive in most patients and there was a trend of normalization during treatment. No relationship between the dose of antithyroid drug and the level of TBII could be seen. During treatment the dose was adjusted according to the FT3I values. This seems to be an adequate laboratory test for this purpose.

Adult↗

Salt-induced exposure of high affinity thyrotropin receptors on human and porcine thyroid membranes.

Thyropin binding to high affinity receptors on human and porcine membranes was studied at pH 7.4, 37 degrees C, in 10 mM Tris-HCl, 150 mM NaCl, 0.1% albumin. By preincubating the membranes in high salt concentration before binding studies, the number of high affinity receptors could be increased 4- to 8-fold. The salt-induced exposure of high affinity TSH receptors was pH- and temperature-dependent and was maximal at pH 5.0, 37 degrees C in the presence of 1 M (NH4)2SO4. Other salts tested, including NaCl, HN4Cl, and Na2SO4, were also able to increase high affinity THS binding. The receptors exposed by salt were indistinguishable from those present on the membranes before such treatment. They had an affinity constant of 0.5 to 1 X 10(10 M-1, and a high TSH specificity with no inhibition of 125I-TSH binding in the presence of a thousandfold excess of gamma-globulin, thyroglobulin, corticotropin, cholera toxin, and gangliosides. Thyrotropin binding to low affinity TSH binding sites (affinity constant 1 to 3 X 10(7) M-1) measured at pH 6.0, 4 degrees C in 10 mM Tris/acetate, 0.1% albumin was unaltered by pre-exposure of membranes to high salt concentrations. These receptors had low TSH specificity and binding was inhibited by gamma-globulin, thyroglobulin, cholera toxin, and gangliosides. The salt-induced selective exposure of high affinity receptors with unaltered number of low affinity sites is further support for the existence of two separate TSH binding sites on thyroid membranes.

Ammonium Sulfate↗

Role of carbohydrates in thyrotropin binding sites.

The role of carbohydrates in thyrotropin binding was studied by glycosidase treatment of human thyroid membranes. Removal of over 75% of membrane sialic acid resulted in a 50% increase of TSH binding, measured in 10 mM Tris-HCl, 50 mM NaCl, 0.1% bSA, pH 7.4, 37 degrees C (buffer A). This augmentation was due to an increase in binding to high affinity sites (Ka 1 X 10(10)M-1). The binding was highly specific and was not significantly inhibited by gangliosides. In contrast, low affinity binding of TSH was unchanged either in buffer A or in 10 mM Tris-acetate, 0.1% bSA pH 6.0, 4 degrees C (buffer B) and was inhibited by gangliosides. Treatment of membranes with beta-galactosidase, beta-N-acetylglucosaminidase and alpha-L-fucosidase had little effect on TSH binding. The data suggests that membrane-associated sialic acid inhibits TSH binding to high affinity receptors and that gangliosides are not involved in tthis TSH-receptor interaction.

Binding Sites↗

Thyrotropin binding to cultured lymphocytes and thyroid cells.

The TSH-binding properties of human lymphocytes in continuous culture were studied and compared to those of bovine and human thyroid cells in primary culture. Both lymphocytes and thyroid cells had maximal TSH-binding capacity at pH 5.2. At pH 7.4, thyroid cells bound 15% but lymphocytes bound only 3% of the amount bound at pH 5.2. At 37 C, maximal binding of [125I]iodo-TSH to lymphocytes was reached within 60--90 min and maximal binding to thyroid cells was reached within 15--20 min. TSH binding to lymphocytes was salt sensitive, being inhibited to 50% by 0.2 mM MgCl and 0.4 mM CaCl2 and by 20 mM Kl, KCl, and NaCl. The saturable binding of bovine TSH (bTSH) to thyroid cells at pHs 5.2 and 7.4 was above 90% of the total binding. Saturable binding of bovine TSH (bTSH) to thyroid cells at pHs 5.2 and 7.4 was above 90% of the total binding. Saturable binding to lymphocytes at pH 5.2 was also above 90%, but at pH 7.4 was 75% of total. At pH 5.2, both cell types displayed identical displacement curves of [125I]iodo-bTSH by unlabeled bTSH. Pure hCG, human placental lactogen, human GH, and insulin cross-reacted to less than 1% with [125I]iodo-bTSH binding to lymphocytes at pH 5.2, whereas a crude preparation of hCG and human FSH plus human LH showed a strong cross-reaction. Nonhormone glycoproteins, including mucin, normal human gamma-globulin, and bovine thyroglobulin showed intermediate cross-reactivity. At pH 7.4, the cross-reactivity of normal human gamma-globulin, bovine thyroglobulin, and pure hCG with bTSH binding to both lymphocytes and thyroid cells was below 1%. The TSH-binding properties of lymphocytes and thyroid cells show many similarities but differ in kinetics and the relative binding capacity at neutral pH. Although the physiological significance of these differences is not yet clear, cultured cells provide a convenient system for studies of TSH-receptor interaction.

Animals↗

Thyrotoxicosis and pregnancy. An analysis of 43 pregnancies in 42 thyrotoxic mothers.

During the period 1965-1976, 43 pregnancies in 42 thyrotoxic mothers were seen. Thirty-nine pregnancies in 38 patients were analyzed further. Twenty-six patients (27 pregnancies) were treated with antithyroid agents with (9) or without (17) supplemental thyroid hormone therapy and 5 were subjected to subtotal thyroidectomy. In these groups spontaneous abortion occurred in 4 patients (12.5%), prematurity in 3 (9.4%) and perinatal death in one whereas 25 pregnancies ended at term (78%). Two pairs of twins were born and the number of live children in these 32 pregnancies was 29. Hypothyroidism developed in one patient after operation. Thyroid crisis occurred at delivery in one patient in whom the antithyroid therapy was interrupted before labour. Seven patients were not treated with specific antithyroid therapy. In this group there was one twinbirth, one premature birth, one stillbirth and one child died shortly after birth. Thyroid crises developed at delivery in two mothers. The authors use subtotal thyroidectomy if usual indications for operation are present and antithyroid therapy when the thyroid gland is small and diffuse. Beta-receptor blocking agents are recommended only as adjuncts to the antithyroid therapy. A close surveillance of the patients and the free thyroid hormone level during therapy is important and after thyroidectomy treatment with thyroid hormone is recommended until after delivery.

Abortion, Spontaneous↗

Thyrotoxicosis during pregnancy.

The diagnosis of thyrotoxicosis during pregnancy is difficult on clinical grounds only. The determination of free thyroid hormones or free thyroid hormone indices is important and is possibly supplemented by the TRH stimulation test. Thyrotoxicosis during pregnancy should always be treated actively. The authors recommend subtotal thyroidectomy if there are indications for surgical therapy (nodular goitre or large diffuse goitre). Otherwise treatment with thyrostatic agents is used. After operation during pregnancy, substitution with thyroid hormones should be given throughout the pregnancy in order to avoid deterious effects of possible maternal hypothyroidism. Antithyroid treatment should be continued till after delivery. Beta-receptor blockers are used only as adjuncts but are not recommended as the sole therapy.

Adrenergic beta-Antagonists↗

Ovulation induction increases serum levels of insulin-like growth factor binding protein 1.

The effect of ovulation induction on serum insulin-like growth factor binding protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG) levels was evaluated. Serum samples were collected 8 to 12 days after ovulation from 26 women undergoing ovulation induction with clomiphene citrate (CC), and from 58 women treated with CC in combination with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were obtained from 63 spontaneously ovulating women and from 12 women during an anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95 micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP-1 levels correlated positively to SHBG levels (r = .52, P less than .001). The data show that ovulation induction increases serum IGFBP-1 levels in parallel to SHBG levels, indicating that ovarian stimulation, which results in increased steroid hormone production, also induces changes in other factors known to modulate steroid hormone actions.

Anovulation↗

Histochemically demonstrable phosphotyrosyl-protein phosphatase in normal human breast, in benign breast diseases and in breast cancer.

The activity of phosphotyrosyl-protein phosphatase enzyme was investigated by a histochemical method in the normal human breast and in breast diseases in order to evaluate its possible significance in the genesis and in the growth of benign and malignant epithelial proliferative. In normal human breast tissue only a weak enzyme activity was present. The activity was elevated in benign disease in actively proliferative lesions and in 71% of the cases of breast cancers. When enzyme activity of breast cancers was compared with the content of receptors for epidermal growth factor and insulin-like growth factor-I, no association was found. It is concluded that phosphotyrosyl-protein phosphatase is increased in actively proliferating human breast diseases. Thus the putative increase in phosphotyrosyl-proteins mediating benign and malignant epithelial proliferations is rather caused by an increase in protein-tyrosine kinase activity than by a decrease in phosphotyrosyl-protein phosphatase activity.

Breast↗