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Biomedical subjects

F Pekonen

Publications and source records attributed to F Pekonen.

At least 55 records · Page 3Linked to original sources

Human chorionic gonadotropin (hCG) and thyroid function in early human pregnancy: circadian variation and evidence for intrinsic thyrotropic activity of hCG.

To explore the diurnal variation and the relationship between serum hCG levels and thyroid function during pregnancy, 26 women with an uncomplicated early pregnancy were studied before and after interruption of pregnancy. The high serum hCG levels in early pregnancy were accompanied by an increase in serum thyroid hormone and a decrease in serum TSH levels. Nevertheless, serum TSH exhibited diurnal variation similar to that in nonpregnant women. The nocturnal surge of TSH exceeded the daytime nadir by 112% and was distinctly different from the normal serum cortisol variation. The diurnal serum T4 and hCG variations were similar to the variation in serum protein concentrations. After pregnancy interruption, serum hCG levels decreased by 95% within 10 days, and TSH levels rose concomitantly from 0.80 to 1.48 mIU/L (P less than 0.001). In individual women serum hCG correlated negatively with TSH (r = 0.322; P = 0.005) and positively with free T3 (r = 0.388; P less than 0.001). These results suggest that hCG has thyrotropic activity, which, through rises in thyroid hormone levels, suppresses TSH secretion. In this regard, 27,000-128,000 IU hCG correspond to 1 mIU TSH. Pregnancy-induced changes in thyroid function, however, do not affect the circadian TSH rhythm.

Adult↗

Different insulin-like growth factor binding species in human placenta and decidua.

Previous studies demonstrated that human decidua secretes a 34K insulin-like growth factor binding protein (34K IGF-BP) earlier designated placental protein 12, whereas placenta contains IGF receptors and IGF mRNA. We studied binding of [125I]IGF-I to paired placental and decidual tissues using competitive binding, gel filtration, RIA, and cross-linking techniques, and compared the binding characteristics of these two tissues which are located in close proximity in vivo. The effect of decidual cytosols on [125I]IGF-I binding to placental membranes also was studied. Consistent with previous data the dominating binding species in placental membranes were IGF receptors. In contrast, the binding of [125I]IGF-I to decidual membranes was mainly due to binding species with mol wts of 34K and 39K. The 34K IGF-BP was more readily detected in decidual cytosols than in decidual membranes and little was detected in placental cytosols. Purified 34K IGF-BP as well as decidual cytosols inhibited [125I]IGF-I binding to placental receptors. The inhibitory effect of decidual cytosol on IGF receptor binding was linearly correlated to the decidual content of 34K IGF-BP. The results suggest that the decidual 34K IGF-BP might act as a local modulator of the IGF action at the interface between the decidua and the placenta.

Autoradiography↗

Receptors for epidermal growth factor and thyrotropin in thyroid carcinoma.

The EGF and TSH receptor properties in malignant thyroid tumours and adjacent normal thyroid tissues were characterized using radioreceptor assays. Ten patients with papillary, 4 with medullary, 1 with Hürthle cell type follicular carcinoma, and 2 with anaplastic thyroid carcinoma were studied. In 10 out of 12 patients with papillary and anaplastic thyroid carcinomas, more EGF receptors were found in the neoplastic tissue than in the adjacent normal tissue (P less than 0.01). The affinity of the EGF receptors varied between patients (from 0.5 X 10(9) l/mol to 1.9 X 10(9) l/mol), but was in each patient the same in the neoplastic and in the normal tissue. In medullary carcinomas and a follicular Hürthle thyroid carcinoma, the EGF receptor content was very low. The receptor number was unaltered or decreased in papillary carcinomas when compared with adjacent normal tissue. In anaplastic medullary and follicular (Hürthle cell) carcinomas, the neoplastic tissue had very few high affinity TSH receptor sites. The alterations in TSH receptor characteristics when thyroid neoplastic tissue was compared with adjacent normal tissue did not correlate to changes in EGF receptor characteristics. Our results demonstrate that the amount of EGF receptors in papillary and anaplastic thyroid carcinomas differ significantly from that in follicular and medullary carcinomas and that alterations in EGF receptor content in malignant thyroid tissues are independent of TSH receptor content.

Adolescent↗

Receptors for recombinant erythropoietin in human bone marrow cells.

Human recombinant erythropoietin, labelled with 125I, was saturably bound to high affinity receptors, ka = 1.5 X 10(9) M-1, of bone marrow cells from 10 patients with various haematological disorders. Binding of labelled erythropoietin was specific, with less than 0.01% cross-reactivities of TSH, hCG and renin substrate (angiotensinogen). Binding capacity averaged 3 X 10(-14) moles/10(6) cells. Binding was maximal within 30 min at 37 degrees C. Low binding, less than 15% of that to bone marrow cells, was found to peripheral blood buffy coat, while erythrocytes and BALL cells did not bind labelled erythropoietin. Autoradiography showed binding of label confined to 4-5% of the bone marrow cells.

Adult↗

Erythropoietin binding sites in human foetal tissues.

Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has an equilibrium association constant of 4.1-6.2 X 10(9) l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 degrees C in 1 h and at 4 degrees C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7 SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41,000 and 86,000 dalton, respectively.

Humans↗

Platelet function and coagulation in normal and preeclamptic pregnancy.

Platelet function and coagulation activity were followed prospectively throughout normal pregnancy and in puerperium in 17 healthy women. Plasma beta-thromboglobulin reflecting platelet activation increased progressively during pregnancy. This was not accompanied by any changes in platelet count or lifespan nor in serum or plasma thromboxane B2 levels. The levels of both factor VIII:C and factor VIIIR:Ag increased, the former less than the latter resulting in a rise of the FVIIIR:Ag/FVIII:C ratio. Antithrombin III (AT III), however remained unaltered. FVIIIR:Ag/FVIII:C ratio was increased both in mild (n = 7) and severe (n = 9) preeclampsia, whereas beta-thromboglobulin was increased and AT III was decreased only in severe preeclampsia. Platelet count and lifespan, plasma and serum thromboxane B2 as well as FVIII:C were normal in severe preeclampsia.

Adult↗

Immunological disturbances in patients with premature ovarian failure.

Eighteen patients with postmenopausal gonadotrophin levels and secondary amenorrhoea before the age of 35 years (premature ovarian failure, POF) were examined for the presence of cellular and humoral immune defects. Six patients had an abnormally low natural killer (NK) cell activity. The levels of circulating immune complexes were increased in six patients. Tissue antibodies were detected in six patients and two of these possessed ovarian antibodies. Leukocyte migration inhibition in the presence of ovarian antigen was slightly enhanced in three patients. Altogether 12 patients (66%) with POF had some immunological defect or defects suggesting that immune mechanisms are often involved in the aetiology of POF.

Adult↗

Renal prostacyclin and thromboxane in normotensive and preeclamptic pregnant women and their infants.

Renal synthesis of the antiaggregatory and vasodilatory prostacyclin and its endogenous antagonist thromboxane A2 may be disturbed in patients with preeclampsia. We tested this hypothesis by measuring 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; a hydration product of prostacyclin), 2,3-dinor-6-keto-PGF1 alpha (generated from 6-keto-PGF1 alpha through beta-oxidation) and thromboxane B2 (a hydration product of thromboxane A2) in the urine of healthy pregnant and preeclamptic women. Urinary excretion of 6-keto-PGF1 alpha [19.8 +/- 10.5 pmol/mmol creatinine, (mean +/- SD)] and 2,3-dinor-6-keto-PGF1 alpha (19.2 +/- 7.5 pmol/mmol creatinine) increased during normal pregnancy, reaching a maximum (about 5-fold rise) during the last month of pregnancy. No significant changes occurred in the urinary excretion of thromboxane B2. In women with severe preeclampsia (n = 17), the excretion of both 6-keto-PGF1 alpha (37.7 +/- 29.5 pmol/mmol creatinine) and 2,3-dinor-6-keto-PGF1 alpha (54.5 +/- 56.2 pmol/mmol creatinine) was lower (P less than 0.001) than in the normotensive women during the last trimester of pregnancy (80.6 +/- 43.7 and 98.7 +/- 42.9 pmol/mmol creatinine, respectively). The neonates excreted 6-25 times more 6-keto-PGF1 alpha, 2,3-dinor-6-keto-PGF1 alpha and thromboxane B2 than did the nonpregnant women. In contrast to the adults, neonatal 6-keto-PGF1 alpha excretion was 2-3 times greater than that of 2,3-dinor-6-keto-PGF1 alpha suggesting reduced beta-oxidation in the newborns. Infants born to preeclamptic women had reduced output of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha on the first day of life. Thus, renal prostacyclin synthesis is diminished in women with severe preeclampsia and their infants.

6-Ketoprostaglandin F1 alpha↗

Naproxen reduces idiopathic but not fibromyoma-induced menorrhagia.

To compare the effect of naproxen on idiopathic and myoma-induced menorrhagia, 11 women with myomatosus uterus and 14 women with idiopathic menorrhagia (menstrual blood loss greater than 80 mL) were treated in a double-blind trial with placebo or naproxen during four consecutive menstruations. Placebo had no effect on menstrual blood loss. Naproxen (500 to 1000 mg daily for five days) reduced menstrual blood loss by 35.7% in women with idiopathic menorrhagia, but it had no consistent effect on myoma-induced menorrhagia. No side effects occurred during naproxen use. Thus, naproxen may prove a suitable treatment for idiopathic but not for myoma-induced menorrhagia.

Adult↗

Antithyroid treatment of maternal hyperthyroidism during lactation.

Eleven pregnant women were treated for hyperthyroidism with carbimazole (CZ) and one with propylthiouracil (PTU). Based upon a previous study it was decided that lactation should be permitted if the dose required after delivery did not exceed 15 mg of CZ or 150 mg of PTU. In the patients studied here the daily dose of CZ varied from 5 to 15 mg and that of PTU was 125 mg. TSH was measured in cord blood and in the blood of the newborn infants usually after 2 and 3 weeks of lactation. Serum T4 was measured serially in the infants' blood from day 4 up to 21 day of age, at least. In all instances the TSH concentration in cord blood remained below 45 mU/l the level used in screening for neonatal hypothyroidism. Serum TSH and T4 were all within the appropriate reference limits during the 3 weeks of study with only one exception. In the infant whose mother was treated with PTU the serum T4 measured 5 d after birth was slightly below the lower limit but later returned to normal. Since serum TSH and T4 did not deviate from the reference range in newborn infants during lactation, we conclude that breast-feeding can be permitted if the daily dose of CZ does not exceed 15 mg (or 150 mg of PTU) and if facilities are available for measuring neonatal serum TSH and T4.

Carbimazole↗

Ontogenesis of the nuclear 3,5,3'-triiodothyronine receptor in the human fetal brain.

A high-affinity T3 binding site with the binding specificity of the nuclear T3 receptor is present in the brain of the human fetus at midgestation. Its concentration was found to be very low at 10 weeks of gestation, and increased by a factor of 10 up to the 16th week, in coincidence with the period of neuroblast multiplication. Liver, heart, and lung also contained receptor. Both T4 and T3 were present in the brain, as measured by RIA. In other tissues, however, only T4 was detected, suggesting that brain T3 in the fetus arises from local 5'-deiodination of T4. The results suggest that the human fetal brain is a potential target of thyroid hormone at midgestation.

Brain↗

Women on thyroid hormone therapy: pregnancy course, fetal outcome, and amniotic fluid thyroid hormone level.

Thirty-four hypothyroid women on thyroid hormone substitution were followed through 37 pregnancies, and 16 women having previous surgery for thyroid carcinoma and thereafter placed on suppressive thyroxine treatment were followed through 19 pregnancies. The thyroxine treatment needed readjustment in 13 pregnancies (23%) to maintain euthyroidism. At delivery, the maternal free thyroxine index was 126 nmol/L in the group of patients treated for hypothyroidism and 146 nmol/L in the patients with treated thyroid carcinoma. The amniotic fluid thyroxine level in normal pregnancies was 6.7 nmol/L, in hypothyroid patients 6.7 nmol/L, and in patients with thyroid carcinoma 5.6 nmol/L. The amniotic fluid reverse triiodothyronine level in normal pregnancies was 0.51 nmol/L, in hypothyroid patients 0.66 nmol/L, and in patients with thyroid carcinoma 0.70 nmol/L. All infants were euthyroid.

Adenocarcinoma↗

Plasma renin substrate in the prediction of pregnancy outcome in threatened abortion.

Concentrations of plasma renin substrate, serum oestradiol-17 beta, human chorionic gonadotrophin, sex-hormone binding globulin and plasma renin activity were measured in 77 samples from 74 patients with uterine bleeding during the first and second trimesters of pregnancy and in a control group of 29 normal pregnant women (51 samples). Mean concentrations of these substances were lower than control values in patients with an abnormal outcome of pregnancy. In patients with a normal outcome after uterine bleeding, concentrations were mostly within the control range. Serum oestradiol-17 beta concentration was superior to the other variables in predicting fetal outcome in the whole group. In patients with a live fetus at the time of blood sampling but who subsequently aborted, serum oestradiol-17 beta concentration was mostly normal, whereas plasma renin substrate was decreased. Our results suggest that plasma renin substrate may provide additional prognostic information to that given by serum oestradiol-17 beta measurement or ultrasonography in threatened abortion.

Abortion, Threatened↗

The interaction of thyrotrophin binding inhibiting immunoglobulins with high and low affinity TSH receptors.

The role of high and low affinity TSH receptors in thyrotrophin binding inhibiting immunoglobulin (TBII) measurements was evaluated. By modifying binding conditions it was possible to observe separately mainly high or low affinity TSH receptors. The greatest difference between TBII positive and negative immunoglobulins was observed when binding to high affinity receptors was measured. In contrast the difference was almost completely lost when low affinity receptors were exposed. The TBII and TSH sensitivity of the radioreceptor assay did however not completely correlate, thus suggesting a difference between TBII and TSH binding sites. During normal pregnancy a high ratio of borderline positive TBII titres was observed in a routine TBII radioreceptor binding assay. Such an assay measures concomitantly both high and low affinity receptors. By using binding conditions measuring preferentially high affinity TSH receptors the TBII positivity in normal pregnancy greatly decreased from 71 to 13%. These results suggest that TBII assay sensitivity and specificity are greatly improved when high affinity TSH receptors are observed. This is especially of importance during pregnancy when false positive TBII indexes are often seen.

Cell Membrane↗

Thyrotropin binding inhibiting immunoglobulins (TBII) in Graves' disease, toxic nodular goitre and autoimmune thyroiditis.

The occurrence of thyrotropin binding inhibiting immunoglobulins (TBII) was studied in 144 patients with different types and stages of Graves' disease (GD) including 2 patients with primary hypothyroidism which changed into hyperthyroid GD. TBII were also studied in 17 patients with toxic nodular goitre (TNG) and 29 patients with autoimmune thyroiditis. TBII was determined with a radioligand receptor assay and expressed as a TBII index which was defined as percentage binding of 125-I-labelled bovine TSH to a thyroid membrane fraction in the presence of test immunoglobulins in comparison with the maximal binding. TBII were positive in 69% of patients with untreated hyperthyroid GD, in 65% after 3-6 months of antithyroid treatment, and in 30-40% 3-114 months after discontinuation of therapy. During treatment the TBII index increased slowly towards normal levels differing significantly from the value before therapy not earlier than after at least 12 months' treatment. Both patients with primary hypothyroidism who developed hyperthyroid GD were strongly TBII positive. In patients with TNG TBII were positive in 24%. In about 30% of the patients with Hashimoto's thyroiditis and with spontaneous hypothyroidism positive TBII were registered. Also in 2 out of 9 patients (22%) with symptomless autoimmune thyroiditis TBII were positive. TBII are not specific for hyperthyroid GD but nevertheless useful humoral markers in several types of thyroid disorder.

Adolescent↗