bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term survival and aldosterone secretion pattern of aldosteronoma in culture
Authors: Okabe Tetsuro , Hidaka Hiroshi , Ohsawa Nakaaki , Tsushima Toshio
Published: December 2008

Abstract. In an attempt to obtain an in vitro experimental model for aldosteronoma, primary culture was initiated with adenomas from 3 patients with primary aldosteronism. The cells grown in culture retained the morphology and functional properties characteristic of aldosteronoma cells well for periods of up to 200 days. The cells formed monolayer cell colonies and showed an epithelioid morphology with small nuclei containing prominent nucleoli. The cells possessed a clear, eosinophilic cytoplasm resembling that of aldosteronoma cells in vivo. The cultured cells continued to secrete large amounts of aldosterone throughout the culture period. The cells responded to angiotensin II and III by increased release of aldosterone into the culture medium. They also responded to Db-cAMP and ACTH by increased secretion of the hormone.
Effects of 2-hydroxyoestradiol and 4-hydroxyoestradiol on gonadotrophin and prolactin secretion in women
Authors: Miyabo Susumu , Kishida Shigeru , Sugiyama Tatsuro , Hashimoto Takuma , Fujii Yoichi , Teranishi Masanori
Published: December 2008

Abstract. In order to investigate the effects of 2-hydroxyoestradiol (2-OHE2) and 4-hydroxyoestradiol (4-OHE2) on the release of human pituitary hormones, each steroid (500 μg single bolus) was injected to young women during the follicular phase. Both steroids resulted in a transient suppression followed by a small rise of LH and FSH. 4-OHE2 appeared to be more potent than 2-OHE2. Injection of only the vehicle caused no change in gonadotrophin levels. The morning fall of plasma Prl was common in young women as an expression of circadian variation. Although the Prl fall tended to be greater in the 4-OHE2 group, analyses failed to reach statistical significance.
Half-life of FSH and LH in the ferret
Authors: Donovan B. T. , Gledhill B.
Published: December 2008

Abstract. Anoestrous and oestrous ferrets were injected with luteinizing hormone-releasing hormone (LRH) or a long-acting analogue and subsequently hypophysectomized. Spayed ferrets were hypophysectomized without prior treatment with gonadotrophin releasing factor, and serial blood samples collected from all animals in order to follow the rate of decline in plasma gonadotrophin concentration. The half-life of LH in the spayed female (around 2 h) was much longer than that of the hormone released from the hypophysis of anoestrous females by LRH (25 min) or by the analogue (19 min). The half-life of FSH released by LRH or analogue in anoestrous females was approximately 65 min, while that discharged by the analogue in oestrous females was about 4 h. The fall in plasma FSH concentration in spayed females after hypophysectomy was too slow to allow calculation of a half-life.
Nuclear thyroxine and 3,5,3'-triiodothyronine receptors in human mononuclear blood cells during pregnancy
Authors: Kvetny Jan , Poulsen Henning Kvist
Published: December 2008

Abstract. Serum free T4, free T3, TSH and maximal nuclear binding capacity for T4 and T3 in mononuclear blood cells were measured in 12 control women, in 12 normal pregnant women in the first and in 12 women in the third trimester. Serum free T4 and T3 were decreased in late pregnancy compared to control women, serum free T4: 9.1 pmol/l (mean) vs 12.9 pmol/l (mean); serum free T3: 4.0 pmol/l (mean) vs 6.2 pmol/l (mean), without any change in TSH levels: 2.2 mU/l (mean) vs 1.8 mU/l (mean). Concomitantly, the maximal nuclear binding capacity for both T4 and T3 increased, T4: 2.7 fmol T4/100 μg DNA vs 1.8 fmol T4/100 μg DNA; T3: 2.8 fmol T3/100 μg DNA vs 2.0 fmol T3/100 μg DNA.

These data, obtained from healthy women during a normal pregnancy are compatible with mild compensated hypothyroidism. We suggest that euthyroidism are maintained by the increased maximal nuclear binding capacity for these hormones.
A case of untreated chronic goitrous autoimmune thyroiditis with spontaneous fluctuation between different metabolic levels
Authors: Solem Jan H. , Svaar Helge
Published: December 2008

Abstract. Documented thyrotoxicosis developed in a 12 year old girl with chronic autoimmune thyroiditis. During the following 3 years there was a spontaneous progression from hyperthyroidism to hypothyroidism and vice versa fluctuating from one metabolic state to another. The diagnosis of Hashimoto's thyroiditis was based upon thyroid function tests, elevated titres of antibodies against thyroid constituents, and upon thin-needle biopsy of the enlarged thyroid gland.
Effects of intrathyroidal metabolism of thyroxine on thyroid hormone secretion: increased degradation of thyroxine in mouse thyroids stimulated chronically with thyrotrophin
Authors: Kubota Ken , Uchimura Hidemasa , Mitsuhashi Tomoaki , Chiu Shoo Cheng , Kuzuya Nobuaki , Nagataki Shigenobu
Published: December 2008

Abstract. Mice were infused continuously with graded doses of bovine TSH (bTSH) and changes in plasma concentrations of bTSH and T4 were measured. Then mice infused with 100 mU TSH per day were sacrificed on days 0, 1, 3 and 5 and their thyroids were excised to determine in vitro secretion of T4, T3 and rT3 during 3 h of incubation. At the end of the incubation, thyroidal contents of T4, T3 and rT3 were also determined after pronase digestion. Plasma bTSH levels were increased on day 1 to a level of 110 μU/ml and remained unchanged thereafter. Plasma T4 concentrations increased approximately 2-fold on day 1, but decreased to initial levels on days 3 and 5. Changes in T4 secretion in vitro paralleled those in plasma T4 concentrations; T4 secretion increased 2-fold on day 1, and decreased to the pre-TSH levels on days 3 and 5. In contrast, T3 secretion increased throughout the experimental period. The T3/T4 ratio in thyroidal secretion in vitro was the same as that in thyroidal contents on days 0 and 1 of TSH infusion, but the former was significantly greater than the latter on days 3 and 5. PTU (5.9 × 10−5 m), a known inhibitor of T4 deiodination, added to the incubation media did not affect T4 secretion on days 0 and 1, but increased T4 secretion on days 3 and 5 to the level of day 1, but did not affect T3 secretion. In the presence of PTU, the T3/T4 ratio in thyroidal secretion did not differ from that in thyroidal contents throughout the experimental period. Secretion of rT3 was increased on days 3 and 5 and PTU augmented this increase. Thyroidal content of rT3 was much increased on days 3 and 5. In contrast, methimazole (10−3 m), which does not inhibit in vitro T4 deiodination, added to the incubation media did not affect T4, T3 and rT3 secretion in vitro. When [125I]T4 was added to the media and incubated with mouse thyroid, no labelled products of T4-deiodination were observed to appear in the media even in mice infused with TSH for 5 days. These results suggest that intrathyroidal metabolism of T4 has physiological significance in controlling thyroid hormone secretion at least in TSH-stimulated thyroids.
Effect of cimetidine on serum carboxyl and aminoterminal fragments of parathyroid hormone in chronic uraemic patients
Authors: Dupont P. , Carlier B. , Marchetti M. , Ducobu J. , Van der Donckt C.
Published: December 2008

Abstract. The effect of cimetidine on abnormally elevated serum levels of parathyroid hormone was studied in 21 patients with secondary hyperparathyroidism due to chronic renal failure, receiving regular dialysis treatment.

The concentrations of carboxyl (-COOH) and aminoterminal (-NH2) fragments of circulating immunoreactive parathyroid hormone (iPTH) were determined before and after 2 months af treatment with cimetidine 400 mg/day.

All patients had, on admission, raised levels of either hormonal fragment. The mean pre-treatment value was 17.2 mU/ml for -COOH terminus (upper normal limit 6.5 mU/ml) and 5.7 mU/ml for -NH2 terminus (upper normal limit 1.9 mU/ml). At the end of cimetidine treatment the mean values were 19.9 and 5.7 mU/ml respectively for the two forms of circulating iPTH. No changes in total serum calcium, phosphate or alkaline phosphatase activity were recorded during the study.

These results do not indicate any lowering effect of cimetidine on serum iPTH in chronic uraemic patients with secondary hyperparathyroidism.
Concomitant falls of plasma cortisol and ACTH levels in a case of Cushing's disease during treatment with trilostane
Authors: Nomura Kaoru , Demura Hiroshi , Imaki Toshihiro , Miyagawa Megumi , Ono Masami , Yano Takashi , Shizume Kazuo
Published: December 2008

Abstract. A 72-year-old man with Cushing's disease was treated with trilostane, a competitive inhibitor of adrenal 3β-hydroxysteroid dehydrogenase (3β-HSDH). The treatment with trilostane successfully lowered urinary excretion of 17-hydroxycorticosteroids (17-OHCS) and plasma levels of cortisol and elevated the plasma level of dehydroepiandrosterone. Unexpectedly, plasma ACTH fell from 109.7 ± 45.0 to 42.7 ± 27.3 pg/ml (P < 0.01) in parallel with plasma cortisol. The hyperresponsiveness of plasma ACTH observed both in the metyrapone test and the lysine-vasopressin test was also ameliorated by treatment with trilostane. Then low dose of pituitary irradiation with cobalt-60 was added and his urinary excretion of 17-OHCS and plasma levels of cortisol decreased further. After treatment with trilostane was finally stopped, the plasma ACTH increased from 45.9 ± 21.9 to 69.6 ± 25.3 pg/ml (P < 0.05) in parallel with plasma cortisol. Since then he has had no recurrence for 12 months. These observations suggest that trilostane, like other adrenal enzyme-inhibiting drugs, may induce unexpected improvement of the abnormality of the hypothalamic-pituitary axis present in Cushing's disease.
Effect of a GnRH analogue on rat granulosa cell lactate production in vitro
Authors: Billig Håkan , Rani C. S. Sheela , Ekholm Carl , Magnusson Claes , Hillensjö Torbjörn
Published: December 2008

Abstract. The effect of a GnRH analogue ((D-Ala6, des-Gly10-NH2)-GnRH-ethylamide,GnRHa) on granulosa and cumulus cell glycolysis in presence or absence of FSH was studied. Cumulus complexes and granulosa cells from PMSG-treated rats were cultured in Eagle's minimal essential medium (MEM) for a period of 72 h. Media were changed at 24 and 48 h and lactate content was assayed by fluorimetry.

GnRHa alone stimulated lactate production in granulosa cells. GnRH combined with FSH increased lactate production in granulosa cells during the 0–24 h period and decreased it during the 48–72 h period as compared to FSH alone. GnRHa did not stimulate lactate production in cumulus complexes during 72 h culture in MEM, while FSH did. In a less complex culture medium, BMOC, GnRHa caused a small increase in lactate production and slightly enhanced the FSH effect.

In conclusion, GnRHa has a direct stimulatory effect on granulosa cell glycolysis. GnRHa also modulates the FSH stimulation of granulosa cells biphasically, i.e. early enhancement (0–24 h) and late inhibition (48–72 h). GnRHa has no consistent direct effects on cumulus cell glycolysis.
The relationship between serum 25-hydroxy-vitamin D levels and other variables related to calcium and phosphorus metabolism in the elderly
Authors: Lamberg-Allardt C.
Published: December 2008

Abstract. Three groups of elderly people (65–80 years) were studied with regard to their vitamin D status: group 1 (Gl), long-stay geriatric patients; group 2 (G2), residents of an old people's home; group 3 (G3), elderly people living in their own homes. Young adults (35–50 years) served as controls (C). The 25-OH-D was significantly lower in G1 (17 ± 7 nmol/l) than in G2 (38 ± 14), G3 (64 ± 23) and C (70 ± 21), (mean ± sd). The concentration in G2 was significantly lower than in G3 and C. The corrected s-Ca concentration was significantly lower in G1 (2.30 ± 0.17 mmol/l) than in any of the other groups (G2: 2.47 ± 0.11; G3: 2.44 ± 0.10; C: 2.39 ± 0.09 mmol/l). The s-ALP activity was significantly higher in all groups of elderly people (G1: 155 ± 43 U/1; G2: 161 ± 61; G3: 143 ± 41) than in C (104 ± 22). The s-Pi concentration was significantly lower in C (1.16 ± 0.14 mmol/l) than in the elderly (G1: 1.43 ± 0.37; G2: 1.30 ± 0.19; G3: 1.28 ± 0.13). The PTH concentrations in some of G1 (0.68 ± 1.14 μg/l) and G2 (0.47 ± 0.41) were higher than in some of G3 (0.30 ± 0.05) and C (0.23 ± 0.07); the difference was not significant. There was a significant negative correlation between the inverse of the 25-OH-D and the s-Ca and the 25-OH-D and s-ALP. In conclusion, the low 25-OH-D, the low s-Ca and the high s-ALP indicate that a fair number of the long-stay geriatric patients and the residents at the old peoples' home suffer from subclinical osteomalacia.
Impaired circadian rhythmicity of β-lipotrophin, β-endorphin and ACTH in heroin addicts
Authors: Facchinetti F. , Grasso A. , Petraglia F. , Parrini D. , Volpe A. , Genazzani A. R.
Published: December 2008

Abstract. The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, β-lipotrophin, (β-LPH), β-endorphin (β-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (β-LPH and β-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a. m. the next morning.

The means of the two 8 a.m. measurements of β-LPH (2.67 ± 0.34 fmol/ml, mean ± se), ACTH (2.74 ± 0.71) and cortisol (218 ± 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 ± 0.61, 10.1 ± 0.74 and 364 ± 27, respectively, P < 0.01) while β-EP concentrations in heroin addicts (5.1 ± 0.6) were similar to those of healthy volunteers (6.44 ± 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol.

In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.

These data show a decreased basal β-LPH, ACTH and cortisol secretion in heroin addicts, despite normal β-EP levels. This would indicate that anterior pituitary proopiocortin synthesis and/or secretion is affected in these subjects, and that there is also some impairment in the structures controlling the circadian rhythmicity of ACTH and related peptides.
Absence of diurnal plasma prolactin rhythm in diabetic and non-diabetic uraemic patients
Authors: Schmitz O.
Published: December 2008

Abstract. The 24 h profile of plasma Prl was studied in 6 non-diabetic uraemic and 5 type I diabetic uraemic patients, the latter brought into a near-normal metabolic and carbohydrate control using an artificial pancreas. Nyctohemeral variation were absent in all 11 subjects (day plasma Prl vs night-levels: 10.1 ± 1.6 ng/ml vs 9.5 ± 1.5 ng/ml, P = 0.09), even in those patients who had a basal Prl within normal limits. Sleep-induced Prl secretion did not re-appear in 5 patients re-studied after several weeks on chronic dialysis treatment (day vs night-levels: 8.9 ± 1.5 ng/ml vs 9.9 ± 1.5 ng/ml, P > 0.10). The absence of night surge was in contradistinction to the Prl profiles observed in 6 healthy subjects (day vs night levels: 6.4 ± 0.9 ng/ml vs 11.3 ± 1.3 ng/ml, P < 0.002) and in 2 type I diabetics with normal kidney function who, as expected, all exhibited a normal circadian Prl rhythm. Brief, episodic Prl secretion during daytime was, however, observed in all the uraemics. The study provides further evidence for a profound dysfunction of the central nervous system in uraemia. The exact mechanism remains unknown.
Primary hypothyroidism followed by hyperthyroidism Five case reports
Authors: Skare Ståle , Frey Harald M. M. , Konow-Thorsen Ragnvald
Published: December 2008

Abstract. Five patients are described, who developed primary hypothyroidism between 25 and 57 years of age. They were all adequately treated with l-thyroxine. Graves' disease developed six months to 34 years later. Two had TSH binding inhibiting immunoglobulin (TBII) in their serum at this stage. All were treated with carbimazole, and 3 have experienced relapse upon withdrawal. Our patients are discussed in relation to the 16 cases previously reported. The pathogenesis of this condition is open to speculation.
Hypoparathyroidism and liver disease – evidence for a vitamin D hydroxylation defect A case report
Authors: Gustafsson Jan , Holmberg Inger , Hardell Lars-Ivar , Foucard Tony
Published: December 2008

Abstract. The case history of a 4 year old girl with primary hypoparathyroidism is reported. Treatment with oral 1α-hydroxyvitamin D3 did not result in normal calcium and phosphate levels, whereas treatment with oral 1α,25-dihydroxyvitamin D3 did. During the treatment period, the patient developed signs of severe liver disease and died in a picture of increased intracranial pressure. Post-mortem examination revealed a giant cell hepatitis and severe cirrhosis. The clinical course is consistent with a liver vitamin D3 hydroxylation defect.
Relation of immunoreactive gastric inhibitory polypeptide to changes in glycaemic control and B cell function in Type 1 (insulin-dependent) diabetes mellitus
Authors: Krarup Thure , Madsbad Sten , Regeur Lisbeth , Faber Ole K. , Tronier Bente
Published: December 2008

Abstract. The effect of strict glycaemic control on plasma immunoreactive gastric inhibitory polypeptide IR-GIP) concentrations and pancreatic B cell function as estimated by plasma C-peptide was evaluated in 14 Type 1 (insulin-dependent) diabetics. The effect was estimated by giving a test meal before (test 1) and after (test 2) 1 week with near normal blood glucose control (mean blood glucose 6.7 ± 0.2 mmol/l) and again 3 weeks later (test 3) in the outpatient clinic. The glycaemic control was significantly improved at test 2 and test 3 compared with that of test 1. The IR-GIP concentrations before and after the meals were similar at all three tests and not different from those found in 21 normal controls. In 8 patients with a significant B cell response at test 1, B cell function was significantly improved both at test 2 and test 3 but no change in fasting or post-prandial IR-GIP concentrations was found and no correlation between B cell function and IR-GIP existed.

We conclude that strict glycaemic control improves B cell function but does not modulate plasma IR-GIP concentrations. Factors other than GIP seem to be of greater importance in determining the magnitude of B cell function in Type 1 diabetes.
The glucagonoma syndrome: stimulus-induced plasma responses of circulating glucagon components IRG9000and IRG3500
Authors: Hendriks Th. , Jansen J. B.J. M. , van Tongeren J. H. M.
Published: December 2008

Abstract. Plasma responses of the major immunoreactive glucagon (IRG) components have been investigated in a case of glucagonoma syndrome. Fasting plasma IRG was 4155 pg/ml. Gel chromatography of plasma revealed that 66% of immunoreactivity was present as IRG9000, while IRG3500 accounted for an additional 26%. The appearance in peripheral plasma of these two glucagon fractions was examined after administration of a number of compounds. IRG levels were clearly elevated after arginine and tolbutamide. Both calcium and calcitonin induced a biphasic rise of IRG, the increase being slower after calcium administration. Somatostatin suppressed plasma IRG levels. All tests induced changes in both IRG3500 and IRG9000. In general, relative changes were more pronounced in IRG3500 than in IRG9000, while absolute changes were greater in IRG9000. The shape of the response curves of IRG3500 and IRG9000 was quite similar after arginine, calcium and somatostatin. After tolbutamide the IRG9000 response was delayed as compared to the IRG3500 component. During the latter part of the calcitonin infusion, IRG9000 remained elevated while IRG3500 was back at its starting level.
Is there an extrathyroidal source of calcitonin during pregnancy?
Authors: Galán F. Galán , Balbontin F. Campoy , Cano R. Pérez , Rubio A. Jimenez , Añon M. Gomez , Peralta M. Garrido
Published: December 2008

Abstract. Calcitonin (CT) and ionic calcium (Ca++) were measured in paired serum samples from the umbilical artery and vein of 47 normal term babies (28 females and 19 males). In the whole group, we found higher CT levels in the vein than in the artery (P < 0.01). Considered by sex, significant CT (P < 0.01) and Ca++ (P < 0.05) gradients existed only in the female group. CT and Ca++ were also measured in serum samples from a group of 26 normal babies (16 females and 10 males) at 2 days of life and in a group of 25 normal babies (12 females and 13 males) at 30 days of life. At 2 day we found a significant increase of CT (P < 0.001) (females P < 0.001 and males P < 0.05), and a significant decrease of Ca++ (P < 0.001) (females P < 0.001 and males P < 0.001), in umbilical artery blood levels at 30 days. Our data show more CT coming from the placenta to the foetus than vice versa, more evident in the females, suggesting an extrathyroidal source of CT, which may be the human placenta. The increase of CT at 2 days, opposing the release of calcium from bone, may contribute in part to the decrease in Ca++ levels observed at that time.
Subcellular distribution of zinc in the benign and malignant human prostate: evidence for a direct zinc androgen interaction
Authors: Leake Alan , Chrisholm Geoffrey D. , Busuttil Anthony , Habib Fouad K.
Published: December 2008

Abstract. The subcellular distribution of zinc and its interaction with androgens has been examined in the benign and malignant human prostate. Endogenously, most of the zinc was associated with the nuclear fraction but significant concentrations were also found in the cytosol. Furthermore, the epithelium contained more zinc than that found in either the stroma or the intact gland. Zinc concentrations were lower in the subcellular fractions of the cancerous tissue when compared to hyperplastic specimens.

In vitro uptake of zinc into prostatic homogenates was rapid and at equilibrium the binding was stable for both the 4°C and the 37°C incubations. At low zinc concentrations (≤ 5 mm) the uptake was higher in the nucleus, whereas at higher concentrations, the cancerous tissue exhibited a greater capacity for the metal which was predominantly retained by the cytosol. Our data suggest the presence of a saturable zinc retention mechanism in the nucleus. The zinc uptake was found to be independent of any added androgen. In contrast, the total androgen uptake by the prostate was significantly enhanced by the addition of zinc. This effect was not due to increases in the nuclear and cytosolic receptor binding since zinc inhibited the binding of the androgen to these receptors.
Two cases of hereditary diabetes insipidus, with an autopsy finding in one
Authors: Nagai Isamu , Li Ching Huai , Hsieh Shao Ming , Kizaki Tomohiko , Urano Yoshinori
Published: December 2008

Abstract. Two cases of hereditary diabetes insipidus (DI) are described, with an autopsy finding in one. The patients were brothers and 7 other relatives had symptoms of DI. The transmission of the disease in this family seemed to be an autosomal dominant trait with incomplete penetration. Both patients had the incomplete type of DI, which is diagnosed by the response of plasma AVP and the change in Uosm/Posm to 14 h water deprivation. The post-mortem examination in Case 1 showed that there was no atrophy of the supraoptic nucleus and paraventricular nucleus, but immunohistochemical studies revealed, that the paraventricular nucleus scarcely had any vasopressin positive cells in contrast to an autopsy control.

This finding suggests that there may be a congenital defect in AVP synthesis in some cases of hereditary DI.
Thyroid antibodies in blood donors: prevalence and clinical significance
Authors: Bjøro T. , Gaarder P. I. , Smeland E. B. , Kornstad L.
Published: December 2008

Abstract. In sera from 1643 randomly selected blood donors examined in 1979 thyroglobulin antibodies (TGA) were found in 3.4% and thyroid microsomal antibodies (TMA) in 7.0%. TMA, but not TGA, showed significant sex and age relationships. Eighty-two donors with TMA titres ≥ 1600 and/or TGA titres ≥ 128 were available for a follow-up study in 1982. In 69 of these with TMA there was a significantly increased incidence of pathological thyroid function-test values (T4, T3 and TSH) as compared to age- and sexmatched donors without thyroid antibodies. In this group 9 individuals had overt and three latent hypothyroidism, two individuals were found with symptomless autoimmune thyroiditis and one with a non-toxic nodular goitre. Only 2 of these had been diagnosed before 1982, and none recognized before 1979. In addition, the group contained 9 individuals who had been treated because of hyperthyroidism, all except one before 1979. The likelihood of detecting a previously unrecognized hypothyroidism increased with increasing TMA titre. In contrast, the 24 donors with TGA did not show an increased frequency of pathological thyroid function-test- values in 1982.
Anti-TSH receptor antibodies in Graves' disease modulate the kinetic behaviour of autologous thyroid TSH receptors. Evidence of the IgG-induced cross-linkage of autologous TSH receptors
Authors: de Bruin Tjerk W. A. , van der Heide Daan , Krol Maria C.
Published: December 2008

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors.

Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.
Pancreatic islet volume distribution: direct measurement in preparations stained by perfusion in situ
Authors: Bonnevie-Nielsen Vagn , Skovgaard Lene Theil
Published: December 2008

Abstract. The islets of Langerhans in normal mice were analyzed and quantitated morphologically after selective in situ perfusion staining with dithizone of the isolated pancreas. Total islet area and number of islets were determined in a texture-analyzing system on projected images of each islet. Islets varied considerably in size and in shape and did not conform with ideal spheroids or ellipsoids. In order to derive methods for estimation of the total number and total volume of islets, a distributional study of the areas was carried out. The size distribution of the islets of Langerhans was not of a known simple type, and was fitted best with a (power)generalized inverse Gaussian distribution.
Glibenclamide is exceptional among hypoglycaemic sulphonylureas in accumulating progressively in β-cell-rich pancreatic islets
Authors: Hellman Bo , Sehlin Janove , Täljedal Inge-Bert
Published: December 2008

Abstract. Six hypoglycaemic sulphonylurea compounds were compared with regard to their ability to bind to β-cell-rich pancreatic islets microdissected from ob/ob mice. Glibenclamide differed from carbutamide, tolbutamide, chlorpropamide, glibornuride and glipizide in not being rapidly bound to an equilibrium, but accumulating progressively in amounts far exceeding the water space. An inhibitor of the anion channels in the β-cell membrane, 4-acetamido-4'-isothiocyanate-stilbene-2,2'-disulphonic acid (SITS), suppressed the islet uptake of glibenclamide and to some extent also that of carbutamide and glibornuride. The unusual uptake characteristics of glibenclamide had their counterpart in a retardation of its maximal action in promoting the entry of Ca2+ into the β-cells.
The nuclear 3,5,3'-triiodothyronine receptor in human leukaemic cell lines
Authors: Bernal Juan , Andersson Leif C.
Published: December 2008

Abstract. The 3,5,3'-triiodothyronine (T3) receptor has been studied in a series of continuously growing human leukaemic cell lines. High concentrations of receptor were found in the erythroblastoid cell line K-562. T3 was bound to the nuclei of these cells with an association constant of 3.4 × 109 m−1, and capacity 104 fmol/100 μg DNA, or 8700 molecules/nucleus. This capacity is comparable to that of rat liver or growth hormone producing cells (GH cells) in culture, and suggests that the K-562 cell line could be a useful model for the study of T3 action on erythroid differentiation.
The value of β-lipotrophin measurement during the short metyrapone test in patients with pituitary diseases and in Cushing's syndrome
Authors: Abou-Samra A. B. , Fevre-Montange M. , Pugeat M. , Dechaud H. , Chalendar D. , Estour B. , Tourniaire J.
Published: December 2008

Abstract. Serum 11-deoxycortisol (S) determination has been used to evaluate the pituitary adrenal response to the short metyrapone (MTP) test. The validity of this indirect evaluation of corticotrophin ACTH reserve has been questioned since the MTP-induced S elevation may reflect a passive accumulation rather than an ACTH activated adrenal response. The purpose of this study was to evaluate the usefulness of serum β-lipotrophin (β-LPH) measurement during the short midnight MTP test (30 mg/kg body weight) in patients with pituitary diseases (n = 36) and in patients with Cushing's syndrome (n = 8). In 28/36 patients with pituitary diseases both S and β-LPH concentrations were increased normally by MTP. In 8/36 patients the β-LPH response was lacking, while their serum S concentrations increased significantly. The absence of β-LPH response to MTP in these 8 patients was in good agreement with the diagnosis of ACTH insufficiency because in 7 of them the cortisol response to insulin induced hypoglycaemia was also insufficient.

In the 8 patients with Cushing's syndrome serum S concentration increased following MTP administration in all the cases. In 2 with adrenal adenoma the increase of S level was an ACTH-independent phenomenon, since β-LPH level was undetectable both before and after MTP administration. In 2 patients with ectopic ACTH secretion, the basal β-LPH concentrations were high and remained unmodified by MTP administration. In the 4 patients with Cushing's disease, MTP administration resulted in a dramatic increase of β-LPH concentration. We conclude that β-LPH measurement improves the utility of the short MTP test for investigation of pituitary adrenal function.
Prolonged combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate causes long-lasting suppression of the autonomous and the LRH-stimulated secretion of luteinizing hormone and follicle stimulating hormone. An in vitro study
Authors: Schuiling G. A. , Moes H. , Koiter T. R.
Published: December 2008

Abstract. The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and oestradiol benzoate (EB) on the autonomous and the 'supra-maximally' LRH-stimulated in vitro release of LH and FSH by pituitary glands of 2 weeks ovariectomized (OVX) rats was studied using a perifusion system. The concentration of LRH in the perifusion medium was 1 μg/ml.

Pre-treatment with LRH during 6 days was effected by means of sc implanted Alzet® osmotic minipumps (MP). Control rats received a piece of silastic with the dimesions of a minipump ('sham-pump'; Sh-P). EB, 3 μg/injection or solvent (arachis oil) was sc injected on days –3 and –1 (day of perifusion: day 0).

Of the pituitary glands of EB-injected, Sh-P-implanted rats both the autonomous and the LRH-stimulated secretion of LH and the LRH-stimulated secretion of FSH were significantly higher than those of the oil-injected, Sh-P-implanted rats without EB administration. Pretreatment with LRH for 6 days had a suppressing effect on the autonomous and the LRH-induced depletion of the pituitary LH and FSH stores. In combination with EB, the suppressing effect of LRH pre-treatment on the LRH-stimulated secretion of LH and FSH was still greater: the pituitary gland appeared to be fixed in a relatively unresponsive state with very low autonomous LH and FSH secretion.

It is discussed that increase of pituitary LRH-responsiveness due to EB demands withdrawal of the pituitary gland from the influence of LRH, an effect which is in vivo achieved by the negative feedback of oestrogen on the hypothalamus.
Precocity of the endothelial proliferation during a course of rapid goitrogenesis
Authors: Many M.-C. , Denef J.-F. , Haumont S.
Published: December 2008

Abstract. Thyroid hyperplasia was induced in C3H mice by a low iodine diet feeding supplemented with propylthiouracil. The morphological modifications associated to the development of hyperplasia were analyzed at light microscopical level and the cellular proliferation was studied by autoradiography after a pulse labelling with [3H]thymidine.

The initial modification during the course of hyperplasia is the development of the vascularization. It includes the dilatation of the capillaries, which occurs before any extended modification of the follicular cells and any change of the thyroid weight, and the proliferation of endothelial cells which starts earlier than that of follicular cells.
The presence of autoantibodies directed to thyroid plasma membrane antigens in sera of patients with thyroid disorders, estimated by the reaction with labelled protein A
Authors: Gardas Andrzej , Czarnocka Barbara , Nauman Janusz
Published: December 2008

Abstract. The presence of antithyroid plasma membrane antibodies (ATMA) has been detected in 97% of patients with untreated hyperthyroid Graves' disease, 85% of methimazole treated hyperthyroid Graves' disease, 25% of Hashimoto's thyroiditis and 6.9% of patients with toxic nodular goitre. The ATMA index was negative in all healthy blood donors, in patients with non-toxic nodular goitre, with the thyrocardiac syndrome and with simple obesity. Studies of patients with non-thyroid autoimmune diseases revealed that ATMA is positive in 11% of patients with scleroderma, 17.6% of systemic lupus erythematosus and 16% of rheumatoid arthritis. The amount of immunoglobulin bound to thyroid plasma membranes after pre-incubation with serum from patients with Graves' disease varied from 4.2 to 25.2 pmoles per mg of membrane protein; these values are several times higher than the maximal binding capacity for thyrotrophin which is 1.28 pmole/mg protein. In the majority of the cases studied TSH did not significantly inhibit IgG bound from thyroid plasma membranes. Significant amounts of IgG were displaced by an excess of TSH only in three cases with untreated hyperthyroid Graves' disease.
Phosphate flush and glucose metabolism in pancreatic islets of young and old diabetic mice (C57BL/KsJ-db/db)
Authors: Berglund Ove , Sehlin Janove , Täljedal Inge-Bert
Published: December 2008

Abstract. Pancreatic islets from normal C57BL/KsJ–+/+–mice and diabetic C57BL/KsJ-db/db-mice were collagenase-isolated and incubated with 33P-labelled inorganic phosphate. No significant difference was observed in phosphate uptake between normal and diabetic mouse islets whether the animals were young (6–8 weeks) or old (27 ± 9 weeks). When 33P-labelled islets were perifused with non-radioactive medium, all types of islets exhibited a brisk and transient peak of phosphate release in response to a change of glucose concentration from 2.8 to 16.7 mmol/l. Expressed in absolute terms, both the basal and peak efflux of phosphate appeared to be diminished in the diabetic mice. In relative terms (peak over basal), the glucose-stimulated phosphate efflux was not lower in diabetic than in normal mice. At both a low (3 mmol/l) and a high (20 mmol/l) glucose concentration, the production of 3H2O from d-[5-3H]glucose was reduced in old but not in young diabetic mouse islets. The percentage increase in glucose metabolism in response to a rise in glucose concentration from 3 to 20 mmol/l was about the same in all types of islets. The results add to previous observations of disturbed ionic fluxes in the pancreatic islets of diabetic KsJ-db/db-mice. These effects are probably not due to gross alterations in glycolytic metabolism but more probably reflect alterations in the function of the β-cell plasma membrane.
Evidence of altered dopaminergic modulation of Prl, LH, FSH, GH and TSH secretion during chronic partial dopamine receptor blockade in normal women
Authors: Hagen Claus , Andersen Anders Nyboe , Djursing Henning
Published: December 2008

Abstract. In order to study the influence of chronic, partial dopaminergic blockade on pituitary secretion of Prl, TSH, GH, LH and FSH, 8 normally menstruating women were given metochlopramide (MTC, Primperan®) 7.5 mg daily for 4 weeks. Based on weekly measurements of progesterone, all cycles were ovulatory. Prior to and after 4 weeks of drug administration serial measurements of basal hormone levels as well as the acute alterations after 10 mg of MTC iv were assessed during the early follicular phase. Chronic MTC administration significantly increased serum Prl (P < 0.02), reduced basal levels of LH (P < 0.02), whereas basal serum concentrations of TSH, GH and FSH were not changed. Before chronic administration iv MTC evoked significant increments in serum Prl (P < 0.001), TSH (P < 0.001) and GH (P < 0.005). The acute TSH increments were significantly (P < 0.02) diminished after 4 weeks of treatment.

The influence of chronic MTC administration on serum LH and TSH levels may be the result of a competitive effect of a stimulatory influence of the dopamine receptor blocker and an opposing inhibitory influence of an increased hypothalamic dopamine activity, evoked by the MTC induced hyperprolactinaemia. Our data favour that the latter mechanism is dominating in normal women, during chronic administration of a low dose of MTC.
Cyclic and diurnal alterations in the response of luteinizing hormone and prolactin to prostaglandin E2 during the rat oestrous cycle
Authors: Wogensen Lise , Warberg Jørgen
Published: December 2008

Abstract. Two μg of prostaglandin E2 (PGE2) was infused into a lateral ventricle of the brain of female rats at 09.00 or 13.00 h on the different days of the oestrous cycle and the effect on luteinizing hormone (LH) and prolactin (Prl) release was determined. At 09.00 h PGE2 caused a pronounced release of LH in pro-oestrous, oestrous and metoestrous rats whereas the LH response in dioestrous rats was moderate. The secretion of Prl was only stimulated in rats from the pro-oestrous phase. When infused at 13.00 h PGE2 had a marked stimulatory effect on the release of LH in all groups of rats. The response was almost the same in oestrous, metoestrous and dioestrous rats but pro-oestrous rats a 2-fold higher LH response was observed. On each day of the oestrous cycle it was found that the LH-releasing activity of PGE2 was greater at 13.00 h than at 09.00 h. Thus, the overall greatest responsiveness of LH to PGE2 was noted at 13.00 h on pro-oestrus i.e. at a time which was prior to the onset of the spontaneous LH surge. At 13.00 h – as at 09.00 h – PGE2 was only capable of stimulating Prl release in pro-oestrous rats. Resembling the LH response it was found that PGE2-induced Prl release was greater at 13.00 h than at 09.00 h. In adult male rats the stimulatory effect of PGE2 on LH and Prl release was independent of the time of administration. It is concluded that the neuroendocrine elements of the hypothalamo-pituitary unit in mature female rats exhibit cyclic as well as diurnal alterations in the responsiveness to PGE2.
TSH-containing pituitary adenoma associated with primary hypothyroidism manifested by amenorrhoea and galactorrhoea
Authors: Wajchenberg Bernardo Léo , Tsanaclis Ana Maria C. , Marino Raul
Published: December 2008

Abstract. A 30 year old woman with primary hypothyroidism due to an ectopic (sublingual) thyroid, with a pituitary tumour invasive to the sphenoidal sinus presented with hyperprolactinaemia, amenorrhoea and galactorrhoea not corrected by long-term thyroid replacement. High basal TSH and TRH hyperresponsiveness were suppressed by thyroid therapy. After transsphenoidal removal of the tumour the Prl returned to normal. Light microscopy including differential staining and immunocytochemistry demonstrated that the tumour was composed of TSH cells. Ultrastructurally the adenoma cell contained small granules (90–150 nm) as described in TSH cells. This case provides evidence that a TSH cell adenoma probably arising from protracted overstimulation secondary to thyroid deficiency can induce hyperprolactinaemia. This did not appear to be produced directly by the adenoma nor was there any evidence of compression of the pituitary stalk.
Transitory subclinical and permanent hypothyroidism in the course of subacute thyroiditis (de Quervain)
Authors: Lio Serafino , Pontecorvi Alfredo , Caruso Michela , Monaco Fabrizio , D'Armiento Massimo
Published: December 2008

Abstract. Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1–40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies (MsAb), in order to study the natural course of the disease and to characterize its intermediate phase.

In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism.

TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism.

Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.
In vitro thyrotrophin release with thyrotrophin-releasing hormone and an analogue, DN-1417
Authors: Shiota Kunio , Yoshida Keiji , Noguchi Chieko , Nakayama Ryo
Published: December 2008

Abstract. Using dispersed and primarily cultured cells of rat pituitary glands, thyrotrophin (TSH) release by TSH-releasing hormone (TRH) and an analogue, γ - butyrolactone - γ-carbonyl - l - histidyl - l - prolinamide (DN-1417) which is more potent than TRH on central nervous system behavioural paradigms, was examined under conditions of static incubation and superfusion. Static incubations of the cells with different concentrations of DN-1417 (10−7–10−4 m) and TRH (10−10–10−6 m) resulted in a dose-related increase of TSH release and the response to both peptides, in logarithmic doses, was in parallel. The potency of DN-1417 related to TSH release was 0.14–0.26% that of TRH. Maximal TSH release induced by DN-1417 (10−5 m) was slightly but significantly greater than that by TRH (10−7 m) In the presence of 3-isobutyl-1-methylxanthine, the TSH response to either of the peptides was augmented, and the difference in the maximal TSH release by either peptide became insignificant, suggesting that TRH as well as DN-1417 act through the same mechanism of mediation by the cyclic nucleotides. In the superfusion study, a biphasic profile of TSH release was observed during a continuous exposure (100 min) to maximal doses of either the analogue or TRH. The biphasic release of TSH was thought to be specific to TRH action because high K+ produced a different profile of the release. These results indicate that the potency of DN-1417 in TSH release is considerably lower than that of TRH, and also suggest that the direct action of DN-1417 on TSH release is qualitatively similar to that of TRH.
The effects of hormone implants on serum lipoproteins and steroid hormones in bilaterally oophorectomised women
Authors: Farish E. , Fletcher C. D. , Hart D. M. , Azzawi F. Al. , Abdalla H. I. , Gray C. E.
Published: December 2008

Abstract. Serum lipoproteins were measured over a period of 6 months in 14 oophorectomised women treated with oestrogen implants (50 mg oestradiol-17β) and 17 oophorectomised women treated with oestrogen/testosterone implants (50 mg oestradiol-17β, 100 mg testosterone). Both types of implant caused only minimal changes in lipoprotein metabolism. Low density lipoprotein (LDL) cholesterol decreased with both types of implant and high density lipoprotein (HDL) cholesterol rose with the oestrogen implants. HDL subfractions were also measured. The oestrogen implants caused a transient rise in HDL2 cholesterol levels at 2 months and a slower rise in HDL3 cholesterol. The oestrogen/testosterone implants had no effect on HDL fractions. The results indicate that hormone implants do not cause the profound changes in lipoproteins associated with oral hormone therapy.