bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal modification of the growth and metabolic effects of a transplantable rat insulinoma
Authors: Flatt P. R. , Bailey C. J. , Swanston-Flatt S. K.
Published: December 2008

Abstract. The growth and metabolic effects of a transplantable radiation-induced rat insulinoma were examined in intact male and female New England Deaconess Hospital (NEDH) rats, and in parathyroidectomised or adrenalectomised male NEDH rats. Subscapular transplantation of insulinoma fragments in intact male rats consistently produced a highly vascularised encapsulated tumour associated with hyperphagia, hyperinsulinaemia and hypoglycaemia which progressed to fatal neuroglycopaenic coma by 30 ± 0.8 days (mean ± sem) and 19 ± 0.5 days for slow-growing and fast-growing tumour sublines respectively (P <0.001). In intact female rats transplanted with the slow-growing subline, the onset of hyperphagia was advanced by 4 days and the severity of hyperinsulinaemia and hypoglycaemia increased (21% and 36%; P < 0.01 and P < 0.001, respectively), resulting in a 10% decrease of survival time (P < 0.05) and a 65% reduction of tumour weight (P < 0.01). Transplantation of the fast-growing subline into parathyroidectomised male rats, which exhibited a 15–24% (P < 0.05 – < 0.01) decrease of plasma calcium, did not modify either the growth or metabolic effects of the tumour. In contrast, transplantation of this subline into adrenalectomised male rats decreased survival time by 32% (P < 0.001) and reduced final tumour weight by 88% (P < 0.02) without markedly affecting the onset or magnitude of the hyperinsulinaemia. These results indicate that the growth and metabolic effects of the transplantable NEDH rat insulinoma are modified by the presence of ovarian hormones and by adrenal hormones. However, plasma calcium homeostasis after parathyroidectomy did not disrupt the growth and metabolic effects of this tumour.
Enterohepatic recirculation of oestriol: inhibition by activated charcoal
Authors: Heimer G. M. , Englund D. E.
Published: December 2008

Abstract. We have earlier reported on a prolonged effect of orally administered oestriol caused by its enterohepatic recycling after reabsorption from the intestine.

The aim of the present study was to test if oral administration of activated charcoal could inhibit the enterohepatic recirculation of orally given oestriol. Plasma concentrations of unconjugated oestriol were measured using a specific radioimmunoassay (RIA).

Twelve mg oestriol administered orally to postmenopausal women resulted in elevated plasma oestriol levels for more than 24 h. Plasma oestriol fluctuations in relation to meals were seen. When activated charcoal was given 3 h after oestriol administration, the plasma oestriol concentration declined without further fluctuations and returned to the pretreatment value within 6 h. Our data indicate that oestriol given orally undergoes enterohepatic recirculation after reabsorption from the intestine since administration of charcoal, which binds steroids, resulted in a rapidly declining oestriol level. It is concluded that the prolonged oestriol elevation, which is normally seen, is caused by enterohepatic recycling.
Long-term treatment of idiopathic hyperaldosteronim using trilostane
Authors: Nomura Kaoru , Demura Hiroshi , Horiba Nobuo , Shizume Kazuo
Published: December 2008

Abstract. Three patients with idiopathic hyperaldosteronism were continuously treated with trilostane, a competitive inhibitor of adrenal 3β-hydroxysteroid dehydrogenase (3β-HSDH) (3 to 4⅔ years). Trilostane, in conjunction with antihypertensive drugs, effectively decreased plasma aldosterone levels and improved hyperaldosteronism symptoms without undesirable side effects. Trilostane continued to be effective even when treatment was continuous. Rapid ACTH testing (iv bolus of 0.25 mg α1–24 ACTH) was done on the day without trilostane after long-term treatment, and plasma levels of aldosterone and cortisol were compared to those obtained during a pre-treatment period. Results suggest that the inhibitory effect of trilostane on steroid biosynthesis rapidly disappears following discontinuance of trilostane administration even after long-term treatment, and that continuous treatment causes no significant or irreversible change in steroid biosynthesis. These results suggest that trilostane is a safe, feasible therapeutic agent for long-term treatment of idiopathic hyperaldosteronism.
Early prenatal treatment of ewes with testosterone completely masculinises external genitalia of female offspring but has no effects on early body weight changes
Authors: Tarttelin Michael F.
Published: December 2008

Abstract. Treatment of pregnant ewes from day 20 of gestation with 100 mg implants of crystalline testosterone did not cause masculinisation of genitalia or affect growth rates of female lambs. Prenatal treatment from day 20 of gestation with testosterone propionate (1.2 g in divided doses for four weeks) or testosterone cypionate (600 mg in 3 doses over three weeks) completely masculinised the external genitalia of female lambs producing a ventral penis and scrotum with no external vaginal opening: ovaries and uteri were normal. Single male lambs were significantly heavier than female lambs during a 16 week measurement period, but masculinised female lambs were not different from controls. In the twin lamb groups, there were no differences between male and female or treated and control lambs. Body weights of castrated male lambs born as twins were not different from entire controls. It was concluded that testosterone treatment of developing lambs from 20 to 65 days of gestation produces complete masculinisation of external genitalia of female lambs but does not affect body weight during the first 16 weeks of age.
Osmolar stimulation of vasopressin secretion in man: comparison of various protocols
Authors: Vallotton M. B. , Favre L. , Dolci W.
Published: December 2008

Abstract. The osmolar stimulation of vasopressin (AVP) release has been studied in 5 healthy subjects using two comparative protocols (infusion of 5% NaCl over 2 h vs 2.5% NaCl over 3 h). As AVP may be secreted by episodic bursts, AVP plasma concentrations were determined both in discrete plasma samples and in integrated samples drawn continuously by a pump over periods of 30 min. There was an earlier rise of plasma osmolality and AVP during the 5% NaCl infusion, but the final maximal value of plasma AVP did not differ in the two protocols. Plasma AVP rose from 1.3 ± 0.7 to 3.8 ± 1.5 during the 2.5% NaCl infusion and from 1.1 ± 0.1 to 3.9 ± 0.6 pg/ml during the 5% NaCl infusion. In both protocols a significant correlation obtained between the discrete and the integrated values of plasma AVP (r = 0.77 and r = 0.84 respectively, P < 0.05). These results demonstrate that the two protocols of osmolar stimulation are equipotent in releasing AVP and do not induce episodic secretion.
Effects of thyrotropin-releasing hormone and cyclo-histidine-proline on the homeothermic development of neontal rats
Authors: Sato Tamotsu , Kato Taizo , Miyamori Chiaki , Kajiwara Sohei , Murata Akisato , Imura Eiichi , Sakura Naoki , Hashimoto Tadashi
Published: December 2008

Abstract. The effects of thyrotropin-releasing hormone (TRH) and its putative metabolite, cyclo-histidine-proline (cHP), on the homeothermic development of neonatal rats were studied. The daily intrathecal administration of 10−11–10−9 moles of TRH during the second week of age produced a significant rise in body temperature by 3 weeks of age and was followed by a transient period of hypothermia. This effect, which could not be produced by an intraperitoneal injection of 10−7 moles of TRH, was abolished by the simultaneous administration of 6-hydroxydopamine (6OHD). In contrast, intrathecally administered cHP decreased thermogenesis. During TRH treatment, brain norepinephrine (NE) and dopamine (DA) release was accelerated 2- to 4-fold. Two weeks after either TRH or cHP treatment, brain NE and DA were significantly reduced; adrenal NE in cHP-treated rats increased. The weight of the interscapular brown adipose tissue (BAT) was decreased by both cHP and 6OHD. At 3 weeks of age, [3H]guanosine diphosphate binding capacity in BAT mitochondria was reduced by 60% in TRH-treated rats and was associated with reduced mitochondrial levels of α-glycerophosphate dehydrogenase and liver cytochrome C reductase. These results indicate that 1) TRH stimulates central NE release thereby enhancing thermogenesis, 2) cHP decreases heat production, and 3) TRH-induced hyperthermia is associated with changes in mitochondrial exothermic processes. The central TRH-cHP system may modulate the maturation of homeothermic mechanism in neonatal rats.
Multiple endocrine neoplasia with Cushing's syndrome due to paraganglioma producing corticotropin-releasing factor and adrenocorticotropin
Authors: Hashimoto Kozo , Suemaru Shuso , Hattori Teruhiko , Sugawara Masanori , Ota Zensuke , Takata Shinji , Hamaya Kazuo , Doi Kenji , Chrétien Michel
Published: December 2008

Abstract. A male patient with corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH)-producing syndrome is described. Soon after being referred to us the patient developed pneumonia, anaemia, oedema and respiratory distress, and died on the 24th day after admission. Autopsy and histology revealed that he had a rare type of multiple endocrine neoplasia (type 1 + paraganglioma) with a mediastinal paraganglioma, parathyroidal hyperplasia, pancreatic islet cell adenoma, duodenal multiple carcinoid tumours and adrenocortical nodular hyperplasia. It was not possible to examine the pituitary. The paraganglioma contained a large amount of immunoreactive (IR)-CRF (606 ng/g wet weight), IR-ACTH (59.4 ng/g wet weight), IR-human proopiomelanocortin n-terminal (1–76) peptide (hNT, 156.8 ng/g wet weight) and IR-β-lipotropin (β-LPH, 146.9 ng/g wet weight). The major IR-ACTH, β-LPH and IR-hNT were eluted at ACTH-(1–39), β-LPH and hNT marker positions, respectively. Big ACTH was not detected. IR-CRF eluted at the human CRF marker position on Sephadex G-75 chromatography and high performance liquid chromatography (HPLC). The IR-CRF fraction from the HPLC showed CRF bioactivity which paralleled that of synthetic human CRF in monolayer cultured rat anterior pituitary cells. Our results suggest that not only ACTH but CRF produced by the paraganglioma was responsible for the patient's Cushing's syndrome.
Studies of sex-steroid-binding plasma protein (SBP) in Graves' disease before and under antithyroid drug therapy
Authors: Aoki Norihiko , Maruyama Yoshiyuki , Imamura Minoru , Ohno Yasuhiro , Saika Toyohiko , Yamamoto Toshio , Suzuki Yasuyuki , Sinohara Hyogo
Published: December 2008

Abstract. The serum concentration of sex-steroidbinding plasma protein (SBP) was measured with radioimmunoassay for 92 patients with Graves' disease, 36 males and 56 females, as well as 92 age- and sexmatched controls. In 24 male patients with hyperthyroidism, the mean SBP concentration was 6.4 ± 0.2 (mean ± sd) μg/ml, whereas it was 2.3 ± 0.2 μg/ml for the controls. The mean SBP concentration in 28 female patients with hyperthyroidism was 7.4 ± 0.6 μg/ml, whereas it was 3.2 ± 0.6 μg/ml for the controls. In Graves patients who were euthyroid following treatment, SBP levels were decreased near normal in both sexes. There was a significant correlation between T4 and SBP concentrations as well as between T3 and SBP concentrations in patients with Graves' disease in both sexes, with a better correlation in females. Increased SBP in untreated Graves' disease initiated to decline within a month following administration of antithyroid drugs, taking over 3 months to decline to the normal range.
Diminished hepatic triiodothyronine production in Gunn rats
Authors: Saltzman J. R. , Clark D. W. , Utiger R. D.
Published: December 2008

Abstract. The liver is a major site of conversion of thyroxine (T4) to the more active thyroid hormone 3,5,3'-triiodothyronine (T3). Hepatic T4 to T3 conversion is altered by a variety of pathological processes and pharmacological agents. We studied T4 to T3 conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10 000 × g supernatant of liver homogenate was used, and T3 production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 μm, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T3 production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T3 production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100 000 μ g, T4-5'-deiodinase activity was found primarily in the 100 000 × g sediment fraction. Homogygous rat liver 100 000 × g sediment T3 production was 55% of that of the heterozygous rat liver 100 000 × g sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T4-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T3 production in livers from both homozygous and heterozygous rats. Thus the diminished capacity for hepatic conversion of T4 to T3 in homozygous Gunn rats may be due to inhibition of T4-5'-deiodinase activity by high endogenous levels of unconjugated bilirubin.
Failure of GnRH analogue to inhibit serum concentrations of testosterone and 17α-hydroxyprogesterone in hCG-substituted hypogonadotropic hypogonadism
Authors: Vicari Enzo , Mongioi Alessandro , Recupero Domenico , Coniglione Francesca , Macchi Maria , Sipione Costantiono , Calogero Aldo , D'Agata Rosario
Published: December 2008

Abstract. Gonadotropin-releasing hormone analogues (GnRH-A) induce inhibition of testicular function and reduction of serum testosterone (T) in man, but the mechanism involved is still debatable. To elucidate it we studied six patients with hypogonadotropic hypogonadism (HH) in chronic substitution with hCG for correction of androgen deficiency symptoms, and evaluated the effect of addition of GnRH-A to the hCG therapy on plasma levels of T and 17α-hydroxyprogesterone (17 OHP). All patients were treated with 1000 U of hCG im every 3rd day for 24 weeks. After 8 weeks of this regimen, GnRH-A, Buserelin (D-Ser-TBU-EA-LHRH), 200 μg per day sc, was added and given for 8 weeks. After cessation of analogue administration patients were followed for 8 further weeks. The levels of the two steroids did not differ markedly in the pre- and post-GnRH-A period. GnRH-A given for two months did not lower T or 17 OHP levels as in eugonadal men after similar treatment. The median T concentrations during GnRH-A tended to be increased, with plasma values higher (P < 0.025) than the peak values observed during hCG alone. Since administration of Buserelin did not inhibit hCG-sustained steroid levels in these HH patients, it is conceivable that GnRH-A may have lacked a direct inhibitory gonadal effect in such experimental conditions.
HLA-DR3 and DRw6: prognostic factors for the incidence of hypothyroidism in Graves' disease after radioiodine treatment
Authors: Althaus B. , Staub J.J. , Neri T. M. , Hauenstein M. , Müller-Brand J. , Berger W. , Farid N. R.
Published: December 2008

Abstract. Several studies demonstrated a relationship between HLA-B8 and -DR3 and the early course of thyroid function after treatment of thyrotoxicosis. However, the association between certain DR antigens and the outcome of thyroid function years after radioiodine treatment for Graves' disease remains unclear. We therefore determined the HLA pattern in 2 groups of female patients with different severity of hypothyroidism. From a total of 45 patients, 27 had developed pre-clinical hypothyroidism (normal serum levels of T4, FT4 and T3, normal or elevated basal TSH levels, but an exaggerated TSH response to TRH, Group A). Mean follow-up was 111 months (range 36–360 months) for this group. Eighteen patients had become overtly hypothyroid (T4 and FT4 levels in the hypothyroid range and an elevated basal TSH concentration, group B) after a mean interval of 51 months (range: 4–132 months) following treatment. Eighty-seven healthy blood donors served a controls. Positive plasma antibody titres (tanned red cell haemagglutination technique) were observed in 67% of all patients with a preponderance in group B (83% versus 56% in group A, n.s.). The whole group of Graves' disease patients showed the antigens B8, DR3 and Drw6 in 37.8%, 33.3% and 35.6%, respectively (P < 0.02, < 0.05, and < 0.04 vs controls). In patients with pre-clinical hypothyroidism there was a significantly increased prevalence of antigen B8 (P < 0.01) and DR3 (P < 0.05) compared to the control group. In contrast, the overt hypothyroid group showed an augmented frequency of HLA-DRw6 (P < 0.04). Antibody positivity was related to the antigens B8 and DR3 (P < 0.005, < 0.03, respectively). Thus, the presence of B8/DR3 represents a genetic pattern possibly protecting against the development of overt hypothyroidism, at least over several years after 131I-treatment. The presence of DRw6 and the absence of DR3 were associated with an increased risk for overt post-irradiation hypothyroidism.
Effect of vitamin D3 loading and thyroid hormone replacement therapy on the decreased serum 25-hydroxyvitamin D level in patients with hypothyroidism
Authors: Bársony Julia , Lakatos P. , Földes J. , Fehér T.
Published: December 2008

Abstract. Twelve hypothyroid subjects, 13 healthy and 12 healthy women with a slight deficiency of vitamin D were studied to distinguish seasonal changes from the thyroxine-dependent ones. Serum 25-hydroxyvitamin D levels of hypothyroid patients were lower than those of healthy individuals when the sera were obtained in the autumn. In hypothyroid patients a single oral dose of 100 000 IU vitamin D3 resulted in a smaller increase in 25-hydroxyvitamin D concentration than in controls having subclinical exogenous vitamin D deficiency. Substitution therapy with thyroid hormone, started in our study always in autumn, increased the 25-hydroxyvitamin D concentration in hypothyroid patients, which was opposite to the autumn-to-spring variation of this hormone observed in healthy controls. The increase of 25-hydroxyvitamin D, dehydroepiandrosterone and its sulphate values following substitution therapy in the hypothyroid patients may indicate that thyroid hormone(s) is (are) involved in the regulation of steroid hormone synthesis.
Stimulation of thyroid adenylate cyclase activity by sera from patients with non-thyroidal illness
Authors: Kakezono Fumiko , Yamashita Shunichi , Yokoyama Naokata , Morita Shigeki , Kubo Ichiro , Ohtakara Shigeru , Okamoto Sumiaki , Morimoto Isao , Ikari Nobuhiko , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

Abstract. We have previously shown that sera from many hypothyroid patients stimulated adenylate cyclase activity as measured by serum bioactive TSH concentrations produced by FRTL-5 cell line. This TSH-stimulating activity did not correlate with serum immunoreactive TSH. IgG fractions of these sera did not stimulate FRTL-5 cells. The present study was, therefore, undertaken to investigate the thyroid stimulating activity of sera from patients with non-thyroidal illness. Studies were performed in 36 patients with various non-thyroidal illness. In these patients, serum concentrations of T4, free thyroxine, T3, and TSH were determined. In addition, sera were incubated with FRTL-5 cells or porcine thyroid cells in primary culture in the presence of 0.4 mm MIBX, and medium cAMP concentrations were determined by radioimmunoassay. Sera obtained from some patients with various non-thyroidal illness increased cAMP concentrations in culture media of FRTL-5 cells as well as that of porcine thyroid cells. The thyroid stimulating effects of sera were not disease specific and significantly correlated inversely with serum T3 and T4 concentrations. Serum TSH concentrations in these patients were within the normal range even by the newly developed ultrasensitive assay. Although the nature of substance(s) present in sera of patients with low T3 syndrome which stimulates thyroid adenylate cyclase is not entirely known, it is conceivable that there exist mechanisms independent of TSH to compensate the decreased serum T3 levels in low T3 syndrome.
Calcium-channel inhibition in pheochromocytoma
Authors: Favre Laurent , Forster Alain , Fathi Marc , Vallotton Michel B.
Published: December 2008

Abstract. Nifedipine, a calcium-antagonist and potent vasodilator, was tested in three patients with pheochromocytoma. In two patients who were normotensive, nifedipine prevented a rise in blood pressure but not in plasma epinephrine and norepinephrine following the iv injection of the dopamine-antagonist metoclopramide. In another patient who was hypertensive, nifedipine was as effective in lowering blood pressure as labetalol or phenoxybenzamine, and did not modify the elevated plasma and urinary catecholamines. Nifedipine appears to control hypertension in pheochromocytoma, without altering catecholamine levels, suggesting that calcium-channel blockade interferes with catecholamine vascular action but not with tumoural catecholamine release. Calcium-antagonists may be helpful in preventing the pressor complications of provocative tests used in the screening of pheochromocytoma.
Distribution of epidermal growth factor binding sites in the adult rat adrenal gland by light microscope autoradiography
Authors: Chabot J.-G. , Walker P. , Pelletier G.
Published: December 2008

Abstract. The distribution of epidermal growth factor (EGF) receptors was studied in the adrenal gland using light microscope autoradiography which was carried out 2 min after intravenous (iv) injection of [125I]EGF into adult rat. At the light microscope level, the labelling was found over the cells of the capsule and adrenal medullary chromaffin cells. No specific labelling of the steroid-secreting cells was observed. Control experiments indicated that the autoradiography reaction was due to specific interaction of [125I]EGF with its receptor. These results clearly indicate that EGF receptors are present in the majority of the adrenal medulla cells. They suggest that EGF may exert a physiological role in the regulation of rat adrenal medulla.
Interaction of PGF2α with prolactin on the release of cyclic AMP and progesterone from the isolated perfused ovary of the pregnant mare serum gonadotropin-treated rat
Authors: Sogn Jan , Abrahamsson Gun , Janson Per O.
Published: December 2008

Abstract. A newly developed model for perfusion of the isolated rat ovary was employed to study the interactions of Prl with PGF2α in respect to the effects of LH on cAMP formation and progesterone production in the 5 day old corpus luteum of the PMSG-treated rat. An inhibitory effect of PGF2α on both basal and LH stimulated progesterone secretion was found. This block also involved inhibition of the ovarian cAMP release which was not associated with a reduction of the flow of the medium to the ovary. When Prl was present in the medium the PGF2α block of LH-induced cAMP release was reversed. However, Prl failed to restore block of LH stimulation of progesterone secretion in 4 out of 9 experiments, indicating an additional site of action of PGF2α distal to the cAMP in these experiments.
Effect of human chorionic gonadotropin on luteinizing hormone and prolactin binding by testes of bilaterally cryptorchid rats
Authors: Grizard Geneviève , Ladjouze Mériem , André Max , Boucher Daniel
Published: December 2008

Abstract. This study investigates the ability of the testis in the cryptorchid state to bind luteinizing hormone (LH) and prolactin (Prl). For this purpose, rats were made bilaterally cryptorchid at 21 days of age; sham-operated rats were used as controls. At 56 days, the animals were injected with saline or with increasing doses of human chorionic gonadotropin (hCG: 1, 10 or 100 IU) and killed 8 or 24 h after injection. Cryptorchidism and injection of hCG did not alter plasma Prl levels. In cryptorchid rats, both LH and Prl binding expressed in pmol/testis were lower than in shamoperated controls (about 75% and 65%, respectively), but unchanged (LH binding) or increased (Prl binding) when expressed in pmol/g testis. In controls, 100 IU hCG induced a significant decrease in LH binding at 24 h. Prl binding was also significantly lower in controls injected with 100 IU hCG than in those injected with 1 or 10 IU hCG, at 8 h. In cryptorchid rats injected with 100 IU hCG, the LH binding fell 8 h and 24 h after injection; at 24 h, hCG reduced Prl binding. In conclusion, there was a considerable decrease in LH and Prl receptors in the abdominal testes. The negative regulation of these receptors in response to hCG was maintained, but at times and for doses which differed from those observed in scrotal testes.
Testicular regulation and sub-cellular distribution of zinc in the epididymis and vas deferens of rhesus monkey (Macaca mulatta)
Authors: Srivastava Archana , Chowdhury A. R. , Setty B. S.
Published: December 2008

Abstract. The zinc concentration in the epididymis (caput, corpus and cauda regions), vas deferens and caudal lobe of prostate of adult rhesus monkeys was determined by atomic absorption spectrophotometry. Zinc content (μg/g wet weight) was found to be maximum in the prostate (709 μg followed by epididymis and vas deferens. The three segments of the epididymis did not differ from one another in their zinc content (165–177 μg). On a protein basis maximum concentration of zinc was present in the nuclear fraction followed by microsomal, cytosolic and mitochondrial fractions in that order. Ligation of testicular efferent ducts or castration 90 days prior to autopsy caused a marked reduction in zinc concentration in different sub-cellular fractions of the organs examined; castration was relatively more effective in this regard. The importance of androgen and other testicular products in controlling zinc content and the possible physiological role of zinc in the male genital tract are discussed.
Circadian rhythms of 6-sulphatoxy melatonin, cortisol and electrolyte excretion at the summer and winter solstices in normal men and women
Authors: Kennaway D.J. , Royles P.
Published: December 2008

Abstract. Urinary excretion of 6-suphatoxy melatonin, cortisol, potassium and sodium was monitored at four hourly intervals for 24 h in 30 normal subjects at the summer and winter solstices. The 24 h profiles were fitted to sine curves and mean 24-h excretion, time of maximum excretion and amplitude of the curves compared. The excretion of 6-sulphatoxy melatonin was remarkably stable at the two times of the year (24-h excretion 108 ± 6.3 nmol in summer and 105 ± 6.3 nmol in winter, mean ± sem). The time of maximum excretion was significantly delayed in winter by 1 h and 40 min. Urinary cortisol excretion was significantly higher in winter, however, the amplitude was unaltered. The time of maximum excretion of cortisol was significantly delayed by 1 h and 34 min. Potassium and sodium excretion were both unaffected by seasonal influences. These results contrast with results in some animal species in which the duration of the melatonin signal is thought to be the key determinant in subsequent melatonin action. In humans it is likely that the phasing of the melatonin rhythm is of prime importance.
Thyroid function in a cassava-eating population affected by epidemic spastic paraparesis
Authors: Cliff Julie , Lundquist Per , Rosling Hans , Sörbo Bo , Wide Leif
Published: December 2008

Abstract. Thyroid function was studied in a rural population in Mozambique that had been affected by an epidemic of spastic paraparesis attributed to dietary cyanide exposure from cassava. Laboratory investigation on a sample of this population demonstrated very high levels of serum and urinary thiocyanate, indicating a heavy exposure to cyanide. The urinary excretion of iodine was within normal limits, indicating an adequate intake of iodine. The serum levels of FT4I were somewhat decreased and serum FT3I, T3/T4 ratio and TSH were somewhat raised. This hormone pattern suggests an adaptation to the antithyroid effect of thiocyanate, but not overt hypothyroidism. A follow-up study on school children was performed, and it also demonstrated high thiocyanate exposure, adequate intake of iodine, and absence of endemic goitre. The results show that if iodine supply is adequate, the thyroid gland is capable of adaptation to a heavy body burden of thiocyanate without development of overt hypothyroidism or goitre.
Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [33H] glucose studies in healthy subjects
Authors: Schmitz O. , Arnfred J. , Nielsen O. Hother , Beck-Nielsen H. , Ørskov H.
Published: December 2008

Abstract. To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45 mU/kg · min or in identical amounts in pulses of 1½ to 2¼ min followed by intervals of 10½ to 9¾ min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270–294 min: 8.7 ± 0.7 vs 6.8 ± 0.9 ml/kg · min, P < 0.01, and 330–354 min: 8.9 ± 0.5 vs 7.4 ± 0.9 ml/kg · min, P <0.05). The superior efficacy of pulsatile insulin delivery on glucose uptake was not consistently found until after 210 min of insulin administration. In both infusion protocols, endogenous glucose production as estimated by the [3-3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion.
Testosterone and epitestosterone metabolism of single hairs in 5 patients with 5α-reductase-deficiency
Authors: Schmidt J. André , Schweikert Hans-Udo
Published: December 2008

Abstract. 5α-reductase activity was investigated in scalp hair roots in 5 patients with 5α-reductase deficiency and in 10 normal volunteers (5 men and 5 women) who served as controls. Metabolism of [3H]testosterone and [3H]epitestosterone was measured under standardized conditions in 1–4 growing (anagen) hair roots. When the mean values of the 5α-reduced metabolites from testosterone (androstanedione and dihydrotestosterone) or from epitestosterone (epidihydrotestosterone) were compared in both groups, similar values were observed. However, since most of the hair roots were incubated singly, it could be demonstrated that in two patients 20 respectively 24% of the hair roots showed neither dihydrotestosterone nor epidihydrotestestosterone formation. This did not influence the mean values determined for the whole group perceptibly. Our results support the concept that 5α-reductase deficiency is a genetically heterogenous disorder by demonstrating that the enzyme defect is variously expressed in hair roots of affected individuals.
Co-purification of bone resorbing activity and adenylate cyclase stimulating activity from human tumours associated with the humoral hypercalcaemia of malignancy
Authors: Shigeno Chohei , Yamamoto Itsuo , Dokoh Shegiharu , Hino Megumu , Aoki Jun , Morita Rikushi , Torizuka Kanji
Published: December 2008

Abstract. We have partially purified a tumour factor capable of stimulating both bone resorption in vitro and cAMP accumulation in osteoblastic ROS 17/2 cells from three human tumours associated with humoral hypercalcaemia of malignancy. Purification of tumour factor by sequential acid urea extraction, gel filtration and cation-exchange chromatography, reverse-phase high performance liquid chromatography followed by analytical isoelectric focussing provided a basic protein (pI > 9.3) with a molecular weight of approximately 13 000 as a major component of the final preparation which retained both the two bioactivities. Bone resorbing activity and cAMP-increasing activity in purified factor correlated with each other. cAMP-increasing activity of the factor was heat- and acid-stable, but sensitive to alkaline ambient pH. Treatment with trypsin destroyed cAMP-increasing activity of the factor. Synthetic parathyroid hormone (PTH) antagonist, human PTH-(3– 34) completely inhibited the cAMP-increasing activity of the factor.

The results suggest that this protein factor, having its effects on both osteoclastic and osteoblastic functions, may be involved in development of enhanced bone resorption in some patients with humoral hypercalcaemia of malignancy.
Serum concentrations of thyrotropin, thyroxine, triiodothyronine and thyroxine binding globulin in female endurance runners and joggers
Authors: Hohtari H. , Pakarinen A. , Kauppila A.
Published: December 2008

Abstract. The effects of endurance training and season on the function of the anterior pituitary-thyroid axis were studied in 18 female runners and their 12 controls, and in 13 joggers and their 11 controls in Northern Finland, with a large seasonal difference in environmental factors. The serum concentrations of thyrotropin (TSH), thyroxine (T4), free thyroxine (fT4), triiodothyronine (T3), thyroxine binding globulin (TBG) and oestradiol (E2) were measured during one menstrual cycle in the light training season (autumn) and in the hard training season (spring). The responses of TSH to intravenous TRH stimulation were also measured in the luteal phase of the cycle during the hard training season. Endurance running did not affect the basal or TRH-stimulated serum TSH concentrations, while those of T4 and fT4 in runners were lowered in both seasons and that of T3 in the light training season in relation to control subjects. The serum concentrations of TBG were also significantly lower in runners than their controls in the luteal phase in both seasons. The effect of jogging on thyroid hormones was less pronounced. Serum concentrations of TSH, T4, fT4, T3 and TBG were generally slightly higher in spring than in autumn. Strenuous endurance training seems to have minor changes on the function of the thyroid gland. Depressed T4 levels in runners may rather be due to lowered TBG levels than due to direct effect of training. In spring the function of anterior pituitary-thyroid axis is more active than in autumn.
The effect of 1,25-dihydroxy-cholecalciferol on the TRH induced TSH release in rats
Authors: Törnquist Kid , Lamberg-Allardt Christel
Published: December 2008

Abstract. The effect of 1,25-dihydroxy-vitamin D3 (1,25-(OH)2-D3) on the TRH induced TSH release was investigated. Wistar rats were injected with 1,25-(OH)2-D3 (0.05 μg/kg/day) for three days, and TRH was injected iv on the third day. Blood was drawn every 10 min during the following 40 min, and TSH was determined. The TSH release was significantly higher in rats treated with 1,25-(OH)2-D3 than in controls. The rats treated with 1,25-(OH)2-D3 were hypercalcaemic and thus, in order to find out if the effect was mediated through hypercalcaemia rats treated as above, were infused with EDTA (30 mg/kg/100 min) starting 60 min before the TRH test. This treatment made the rats normocalcaemic, and the significant increase in the TSH release was still seen in the 1,25-(OH)2-D3 treated rats as compared to controls. The results thus indicate that 1,25-(OH)2-D3 enhances the TRH induced TSH release and that the effect is not mediated through an increase in the serum calcium concentration at the time of the TRH test. In order to find out if the effect could be mediated by changes in intracellular calcium the rats were treated with the calcium antagonist verapamil (25 mg/kg/day) and the adrenergic blocker propranolol (5 mg/kg/day) alone or together with 1,25-(OH)2-D3. In rats treated with verapamil or propranolol alone or 1,25-(OH)2-D3 + propranolol, no effect was observed on the TRH induced TSH release. Verapamil + 1,25-(OH)2-D3 significantly increased the TSH release as compared to both controls and rats treated with 1,25-(OH)2-D3 alone. The rats treated in this way was, however, hypercalcaemic and remained so also during EDTA infusion. The results in this latter case (verapamil + 1,25-(OH)2-D3) is surprising but could be mediated by an inhibition of dopamine with a release of TSH as a consequence. In this study, however, the mode of action of 1,25-(OH)2-D3 remained unsolved.
Interrelated calcium ion and cyclic AMP inhibition of placental lactogen secretion by cultured human term trophoblast
Authors: Hochberg Z. , Perlman R. , Bick T.
Published: December 2008

Abstract. Calcium ion has been shown to have a negative regulatory effect on the secretion of human placental lactogen (hPL). We report an inhibitory effect of cyclic AMP on hPL secretion in a model system of cultured human term trophoblast. Similar results were obtained by modulation of cyclic AMP-phosphodiesterase. The effects of ionophore A23187 and cyclic AMP were non-additive. In searching for the sequence of the common pathway, we found that the ionophore A23187 reduced cyclic AMP concentration and that the inhibitory effect of cyclic AMP was abolished by verapamil, a calcium channel blocker, and by trifluoperazine, a calcium-calmodulin inhibitor. Cyclic AMP seems to mobilize intracellular calcium, and the latter, by way of a calcium-calmodulin complex, modulates the secretion of hPL.
Comparison of the pharmacological properties of pituitary and biosynthetic human growth hormone
Authors: Jørgensen Karin Damm
Published: December 2008

Abstract. Biosynthetic human growth hormone was compared with pituitary human growth hormone and pituitary 22 K in the weight gain and the tibia test. The three preparations were found to be equipotent. Furthermore, the growth hormones were compared in various pharmacological test systems. All three preparations were found to have a marked antidiuretic and antinatriuretic effect in the rat and to cause a significant shortening of the hexobarbital sleeping time in mice. Biosynthetic and pituitary preparations had the same diabetogenic activity in obese mice, and the growth hormones did not differ with respect to pharmacological profiles in the test systems applied.
Direct immunostaining of TSH receptor related autoantibodies in Graves' disease
Authors: Sellschopp Ch. , Derwahl M. , Schaube H. , Seifert J. , Hamelmann H.
Published: December 2008

Abstract. Ten thyroid specimens from patients with Graves' disease were investigated immunohistologically with respect to the localisation of thyrotropin (TSH) receptor related autoantibodies. After conventional preparation of formalin-fixed and paraffin-embedded thyroid slices for immunostaining, 3–5 μm tissue sections were incubated with a porcine thyrotropin receptor containing membrane preparation (pTSH-R). The TSH receptor containing membrane fragments bound to the thyroid tissue were revealed with a slightly modified unlabelled PAP technique according to Sternberger, using an antiserum to pTSH-R obtained from immunized rabbits. This technique resulted in a staining of a considerable portion of plasma cells within the lymphoplasmacellular infiltrates of all the Graves thyroids. No staining occurred if for negative control either pTSH-R or its antiserum from rabbit was omitted. In addition, the staining reaction was markedly reduced by pretreatment of pTSH-R with serum from patients with Graves' disease in order to occupy its binding sites for autoantibodies prior to the staining procedure.

It is concluded that the staining of the intrathyroidal plasma cells is due to their synthesis of autoantibodies directed against TSH receptor related structures of thyroid epithelia. The results are in keeping with the concept that the thyroid as the target organ itself is the site of autoantibody synthesis in Graves' disease.
Studies of the luteinization process in the rat: follicular and luteal adenylate cyclase responsiveness to catecholamines
Authors: Selstam Gunnar , Norjavaara Ensio , Rosberg Sten , Nordenström Knut , Damber Jan-Erik , Cajander Stefan
Published: December 2008

Abstract. The subject of the study was the development of follicular and luteal catecholamine responsiveness during the periovulatory period. Follicles and corpora lutea and granulosa cells were obtained from the PMSG ovulatory model and adenylate cyclase activity measured in membrane fractions. In the earlier part of the follicular phase (48 h and 26 h before ovulation) no response to noradrenalin on follicular and granulosa cell adenylate cyclase activity was seen. A small but significant response to noradrenalin was observed from 18 h before until 3 h after ovulation. The response to noradrenalin on luteal adenylate cyclase activity increased markedly with time and reached a maximum 39–57 h after ovulation. After this time the luteal response to noradrenalin decreased with luteal age. The effect of LH was less than that of noradrenalin during the early luteal phase, and in contrast to noradrenalin, increased with luteal age. The combined effects of LH and noradrenalin were not additive. In order to test whether gonadotropins could induce a noradrenalin response, injections of LH and FSH were given to the animals two days before ovulation. LH, but not FSH, induced a small but significant response to noradrenalin 16 h later. The present investigation has shown that ovarian responsiveness to catecholamines appears in preovulatory follicles followed by a marked increase in luteal catecholamine responsiveness. This development could at least partly occur under the influence of LH.
The effect of submaxillariectomy on the uterine peroxidase activity and [14C] phenylalanine incorporation into uterine protein in rats
Authors: Banerjee Prithindra N. , Bhattacharyya Jharna , Datta Anima , Datta Asoke G.
Published: December 2008

Abstract. Surgical removal of submaxillary glands in immature female rats caused an increase in size and about 3-fold increase in dry and wet weight of the uterus compared to that of the sham operated animals of the same age group. Histological examination reveal a significant increase in the diameter of the uterus with considerable elongation of the luminal epithelium from cubical to columnar in the experimental group. Biochemical studies showed that the uterine peroxidase, a marker enzyme for oestrogen action, increased (P < 0.01) on submaxilariectomy. Incorporation of [14C] phenylalanine into the nuclear fraction of uterus was also enhanced significantly on removal of submaxillary glands. The elevation of peroxidase activity as well as of [14C]phenylalanine incorporation into the nuclear fraction due to removal of submaxillary glands were abolished in ovariectomized rats suggesting the involvement of ovarian hormones. The results show that oestrogen was responsible for all the above mentioned changes, whereas progesterone had little effect. Results further suggest the existence of a factor in the submaxillary glands through which they exert an effect on the uterus and ovary.
Plasma arginine vasopressin during neck suction in upright sitting man
Authors: Norsk P. , Bonde-Petersen F. , Warberg J.
Published: December 2008

Abstract. In order to examine the influence of carotid baroreceptor stimulation on arginine vasopressin secretion, 8 normal healthy males were subjected to static neck suction of −3.3 kPa for 20 min in the upright sitting position after overnight food and fluid restriction. The plasma concentration of arginine vasopressin did not change significantly during neck suction. However, in 3 subjects the termination of neck suction induced large increases in plasma arginine vasopressin from 1.8 to 63.7 ng/l, from 0.7 to 34.3 ng/l and from 2.1 to 19.0 ng/l, respectively. Two subjects experienced symptoms such as nausea and paleness during neck suction. Systolic arterial pressure increased slightly but significantly during neck suction from 15.3 ± 0.3 to 15.7 ± 0.4 kPa (N = 7, P < 0.05), whereas mean arterial pressure, diastolic arterial pressure, central venous pressure, heart rate, plasma osmolality, plasma sodium and potassium were unchanged. Haemoglobin concentration in blood and haematocrit increased significantly during and after neck suction, whereas plasma volume decreased. We conclude that neck suction with a negative pressure of 3.3 kPa in upright sitting man does not significantly affect plasma arginine vasopressin. However, termination of the stimulation induces large increases in some subjects. This may be explained by a direct effect on the vagus nerve or by a selective deloading of carotid baroreceptors.
The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat
Authors: Shah Jayendra H. , Hurks Charles , Udomphonkul Nikom , Hargis Gary , Williams Gerald A.
Published: December 2008

Abstract. The effect of vincristine on immunoreactive parathyroid hormone (iPTH) release and parathyroid cell microtubular structures was evaluated in intact, unanaesthetized, and unrestrained rats with indwelling catheters. In overnight fasted rats, blood samples were collected before and at 30, 60 and 120 min after iv vincristine administration in low dosage (0.15 mg/kg) or in higher dosage (0.5 mg/kg) or vehicle (controls) for serum iPTH and calcium determinations. Mean baseline serum iPTH and calcium concentrations were similar in the vincristine-treated and the control rat. Following the low dose vincristine treatment, serum iPTH slightly but significantly declined to 89 ± 5% at 30 min and remained at this low level at 60 and 120 min as compared to those observed in control rat. Similarly, iPTH concentrations after higher doses of vincristine were also significantly decreased to 87 ± 4% at 30 min and to 83 ± 4% at 60 min, and 86 ± 7% at 120 min as compared to those observed in the control rat. Serum calcium concentrations were similar in the vincristine-treated and control rats. In the next study, each of the rats received vincristine and vehicle in a random order, 10 days apart. In this study also, mean serum iPTH significantly declined to 85 ± 7% at 60 and 120 min during vincristine treatment as compared with those observed during the vehicle treatment in the same rats. Parathyroid glands were removed from rats between 60 and 120 min after vincristine or vehicle treatments for electron microscopy. Morphometric analysis revealed that the number of microtubules and mean microtubular length of the parathyroid cells were similar in the vincristine-treated rats to those observed in the control rats. Therefore, 1) in the intact rat, even low dosage of vincristine cause significant inhibition of iPTH release and 2) this inhibition occurs in the absence of any morphological alteration in the parathyroid cell microtubular structures.
Oestrogen and thyroxine-binding globulin levels in early normal pregnancy
Authors: Sparre Lottie Skjöldebrand , Brundin Jan , Carlström Kjell , Carlström Anders
Published: December 2008

Abstract. Peripheral serum levels of thyroxine-binding globulin (TBG), unconjugated and total oestrone, and unconjugated oestradiol-17β were measured twice in 60 cases of early normal pregnancy (gestational weeks 6–19). Although highly significant correlations between TBG and oestrogen levels were obtained in the total material, the correlations within two-week intervals of pregnancy were rather poor and mostly insignificant. Furthermore, there were no associations at all between the increase rates of TBG and those of the oestrogens, either within two-week intervals or in the total material. The findings do not support the common concept of continuously rising oestrogen stimulation as the main factor affecting the TBG synthesis during pregnancy.