bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of subcutaneous infusion versus subcutaneous injections of a somatostatin analogue (SMS 201-995) on the diurnal GH profile in acromegaly
Authors: Timsit José , Chanson Philippe , Larger Etienne , Duet Michèle , Mosse Arlette , Guillausseau Pierre Jean , Harris Alan G. , Moulonguet Michel , Warnet André , Lubetzki Jean
Published: December 2008

Abstract. Multiple sc injections of a long-acting somatostatin analogue (SMS 201-995) are currently used in the treatment of acromegaly. However, plasma GH concentration often reaches a pathological level (> 5 μg/l) between two injections. In seven patients with active acromegaly we compared, in a short-term trial, the effect of SMS 201-995 administered by continuous sc infusion (50 μg and 100 μg a day) and by three scinjections (100 μg each). In six patients, plasma GH levels were significantly reduced regardless of the mode and dose of treatment (P < 0.05). However, comparing diurnal profiles, 100 μg continuous sc infusion was more effective than discontinuous administration in reducing the number of GH levels above 5 μg/l (P < 0.01). In two patients, continuous infusion was the only way to decrease all plasma GH values below 5 μg/l during the diurnal profile determination. Moreover, even when, in a long-term study, the dose of multiple injections was progressively increased to 500 μg three times a day, GH levels remained consistently elevated in one of these patients. Thus, in some acromegalic patients continuous sc injection seems currently the most efficient way of treatment with SMS 201-995.
Urinary melatonin, LH, oestradiol, progesterone excretion during the menstrual cycle or in women taking oral contraceptives
Authors: Brun Jocelyne , Claustrat Bruno , David Michel
Published: December 2008

Abstract. Nocturnal urinary excretion of melatonin, LH, progesterone and oestradiol was measured by radioimmunoassay in nine normal women during a complete cycle. In addition, these hormonal excretions were studied in two women taking an oral contraceptive. A high within-subject coefficient of variation was observed for melatonin excretion in the two groups. In the nine normal cycling women, melatonin excretion was not decreased at the time of ovulation, but was significantly increased during the luteal phase compared with that of the follicular phase (P < 0.01). These data are consistent with a positive relationship between melatonin and progesterone during the luteal phase. In the two women under an oral contraceptive, melatonin excretion was found within the same range as for the other nine. The results are discussed in terms of pineal investigation in human.
Vasoactive intestinal polypeptide and dopamine in the hypothalamus and pituitary of ageing rats with prolactinomas
Authors: Prysor-Jones R. A. , Silverlight J. J. , Jenkins J. S. , Merry B. J.
Published: December 2008

Abstract. Vasoactive intestinal peptide (VIP), an dopamine have been measured in the hypothalamus and anterior pituitaries of female rats at three different ages. Rats aged 19 months had a high incidence (35%) of prolactin-secreting tumours of the pituitary and these animals had increased hypothalamic and pituitary VIP compared with three-month-old rats or rats without tumours. VIP in old animals without tumours was similar to that in young animals. The third group, with an even more advanced age of 22–28 months, had a lower incidence of PRL-secreting tumours, and pituitary and hypothalamic VIP concentrations similar to those in young animals. Dopamine was significantly increased in the pituitaries of 22–28-month-old nontumorous rats and slightly raised in 19-month-old rats. We conclude that the increased pituitary and hypothalamic VIP content of 19-month-old rats could be a factor in the development of tumours seen at this age, and the differences seen in the two groups of old rats may be related to changes in the steroid environment.
Adrenal androgens and illness
Authors: Semple C. G. , Gray C. E. , Beastall G. H.
Published: December 2008

Abstract. We have studied the adrenal androgen status of medically ill patients, patients before and after cholecystectomy and during recovery from burns injury. In patients ill for less than 2 weeks, serum androstenedione concentrations (mean ± sem) were raised (7.94 ± 0.98 nmol/l) as compared with a control group (4.83 ± 0.38 nmol/l, P < 0.005) or with patients ill for more than 2 weeks (5.21 ± 0.46 nmol/l, P < 0.02); serum dehydroepiandrosterone sulphate (DHAS) levels were lower in patients ill for more than 2 weeks (1.21 ± 0.42 μmol/l) than in either the acutely ill group (5.98 ± 1.06 μmol/l, P < 0.001) or the control ill group (5.56 ± 0.59 μmol/l, P < 0.001). In post-operative patients serum DHAS levels fell to below pre-operative levels reaching a nadir at day 8 (0.54 ± 0.19 vs 1.66 ± 0.56 μmol/l, P < 0.02). In burned patients serum cortisol levels were increased on admission (661 ± 91 vs 359 ± 30 nmol/l, P < 0.005) and remained high over the study period. Serum androstenedione concentrations were also high on admission (7.5 ± 1.0 vs 3.9 ± 0.3 nmol/l, P < 0.02). Serum DHAS concentrations were similar to control values on admission (6.8 ± 1.2 vs 5.2 ± 0.7 μmol/l), fell to low levels thereafter reaching a nadir during week 3 (1.6 ± 0.6 μmol/l, P < 0.001). Steroid synthesis in times of chronic illness may be diverted from adrenal androgen to corticosteroid pathways ensuring maintained secretion of cortisol, which is essential to the health of ill patients.
Sex difference in growth hormone response to growth hormone-releasing hormone between pubertal tall girls and boys
Authors: Smals A. E. M. , Pieters G. F. F. M. , Smals A. G. H. , Beenraad Th.J. , Kloppenborg P. W. C.
Published: December 2008

Abstract. In adult rats and also in young adults, a sex difference in GH responsiveness to GHRH has been reported with the higher responses in males. In young rats, however, the reverse has been found, i.e. a higher GH response in females than in males. This discrepancy promted us to compare GH responsiveness to GHRH in midpubertal tall girls (N = 10) and boys (N = 8). An iv bolus administration of 100 μg of GHRH to these adolescents disclosed a sex difference in GH responsiveness. At all time intervals up to 30 min after the bolus, the GH responses to GHRH in the girls were significantly higher than in the boys (P <0.025 – P < 0.05), whereas the peak GH increments (34 ± 4 vs 19 ± 3 μg/l; P < 0.02) were about twice as high in the former as in the latter. The data suggest that like in rats, also in humans, sex-related changes in pituitary GH sensitivity to GHRH may be an important factor in the pubertal growth and develo ment at least in tall girls and boys.
Effect of prolactin on the diurnal changes in immune parameters and plasma corticosterone in white leghorn chickens
Authors: Skwarlo-Sonta Krystyna , Sotowska-Brochocka Jolanta , Rosolowska-Huszcz Danuta , Pawlowska-Wojewódka Ewa , Gajewska Alina , Stepień Diana , Kochman Kazimierz
Published: December 2008

Abstract. The effect of PRL on the diurnal changes in peripheral lymphocyte and granulocyte number, antisheep red blood cells, and natural anti-rabbit red blood cells serum agglutinins titre as well as plasma corticosterone concentration was examined in White Leghorn cockerels, immunized twice with sheep red blood cells. PRL was administered for six consecutive days at 4 or 8 h after light onset. Control birds were treated at the same times with hormone solvent alone. Immunized non-treated birds served as an additional control group. PRL injections influenced markedly the diurnal changes in all parameters examined. The effect of PRL administration on the diurnal changes in lymphocyte and granulocyte number and natural anti-rabbit red blood cells serum agglutinins consisted in elimination of the influence of solvent injections. In those cases where the solvent injections did not alter the pattern of the diurnal changes, i.e. in anti-sheep red blood cells serum agglutinins and in plasma corticosterone concentration, the pattern was modified by PRL injections. PRL administration affected also the correlations between the diurnal changes in plasma corticosterone concentration and those in lymphocyte number and anti-sheep red blood cells agglutinin titre. This suggests that the role of PRL in the regulation of the diurnal variations of immunity in chickens may be realized either directly, via its receptors in immune system or by its influence on plasma corticosterone concentration.
Interaction of ovine somatomedin-C/IGF-I and IGF-I with specific IGF-I receptors on cultured muscle-derived fibroblasts
Authors: Dodson M. V. , Mathison B. A. , Hossner K. L.
Published: December 2008

Abstract. Binding of 125I-insulin-like growth factor-I and 125I-ovine somatomedin-C/IGF-I to monolayer cultures of muscle-derived ovine fibroblasts is described. Preliminary competitive binding experiments indicate that ovine fibroblasts possess independent cell surface receptors for IGF-I. Affinity of rIGF-II for IGF-I binding sites is minimal; rIGF-II binds to Type I IGF receptors at 1/1000 the strength of IGF-I. Insulin binds to the Type I IGF receptor at 1/100 the strength of IGF-I, whereas ovine somatomedin-C/IGF-I displays equivalent IGF-I binding as evidenced by overlapping competition of ovine somatomedin-C/IGF-I for 125IIGF-I binding sites. Results from disuccinimidyl suberate cross-linking of 125I-IGF-I to muscle-derived ovine fibroblasts in the presence of related polypeptides verified the competitive binding data. Under reducing conditions, 125I-IGF-I: receptor complexes migrated to a relative molecular weight of approximately 135 000 daltons. Specific 125I-IGF-I binding was completely inhibited by 10−8 mol/l IGF-I, 7.2 × 10−8 mol/l ovine somatomedin-C/IGF-I, and 10−6 mol/l insulin and partially inhibited by 7.2 × 10−9 mol/l ovine somatomedinC/IGF-I and 6.5 × 10−8 mol/l rIGF-II. 125I-ovine somatomedin-C/IGF-I: receptor complexes also migrated at a relative molecular weight of 135 000 daltons. No migratory band was observed at 250 000 to 260 000 daltons with either 125I-IGF-I or 125I-ovine somatomedin-C/IGF-I indicating that little labelled moiety bound to the Type II IGF receptor. Based on these preliminary competitive binding studies and cross-linking data, we conclude that ovine somatomedin-C/IGF-I is primarily interacting with the Type I IGF membrane receptor on ovine skeletal muscle fibroblasts.
Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats
Authors: Varma Santosh K. , Bloch Eric
Published: December 2008

Abstract. The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P < 0.01). Foetal body weights (P < 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P < 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. The results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus. The diminished activity of adult testes indicates a permanent effect of in utero mestranol exposure on testes function.
Calcium-binding proteins and insulin release
Authors: Krausz Yodphat , Eylon Ludmilla , Cerasi Erol
Published: December 2008

Abstract. Calcium and cAMP are interdependent regulators of glucose-induced insulin release. In the present study we investigated the importance of cAMP and calcium-binding proteins for biphasic insulin secretion by assessing the effects of two phenothiazines known to block such proteins, trifluoroperazine (TFP) and promethazine (PMZ). In isolated rat islets, during 60-min incubations with 16.7 mmol/l glucose both agents inhibited the insulin response with ID50 values of 15 μmol/l for TFP and 5 μmol/l for PMZ. Both agents decreased the maximal insulin response without gross changes in the islet sensitivity to glucose. TFP (15 μmol/l), whereas inducing 50% inhibition of second-phase insulin release, totally suppressed the cAMP response to glucose and the accompanying first-phase insulin secretion (5-min incubations); these effects of TFP could be partially reversed by isobutyl methylxanthine (IBMX). In contrast, 5 μmol/l PMZ, which produced 60% inhibition of second-phase insulin release, had no effect on first-phase insulin and cAMP responses to glucose. Furthermore, IBMX did not modify the inhibitory effect of PMZ on second-phase insulin secretion. The following is concluded: 1. TFP acts preferentially on first-phase insulin release and inhibits cAMP formation; this suggests that calmodulin plays a major role in mediating the initial glucose effect on secretion via stimulation of cAMP. 2. The islet probably contains calcium-sensitive proteins other than calmodulin, since the low concentrations of PMZ shown to inhibit second-phase insulin release lack effects on calmodulin. Synexin could be such a protein. 3. PMZ had no effect on cAMP generation and first-phase insulin release; it is speculated that synexin-like proteins may mediate the glucose effect on second-phase release by increasing the responsiveness of the islet to calcium/cAMP.
Macroprolactinomas and functionless pituitary tumours
Authors: Gasser R. W. , Mueller-Holzner E. , Skrabal F. , Finkenstedt G. , Mayr U. , Tabarelli M. , Spoendlin H. , Grunert V. , Twerdy K.
Published: December 2008

Abstract. In 32 patients with macroprolactinomas or functionless pituitary macroadenomas biochemical and clinical data were correlated with PRL immunocytochemistry. Serum PRL levels revealed a positive correlation with tumour PRL content. Hyperprolactinaemia of 3000 mU/l or more was found only in patients with PRL-positive tumours. In 15 patients with borderline hyperprolactinaemia (below 3000 mU/l), 7 PRL-positive and 8 PRL-negative macroadenomas were found, and in 9 normoprolactinaemic patients 4 PRL-positive and 5 PRL-negative macroadenomas. Patients with PRL-immunostainable tumours had significantly higher median basal serum PRL (P ≤ 0.05) than patients with PRL-negative tumours. PRL stimulation after TRH, basal and GnRH-stimulated FSH and LH did not show significant differences between the two groups. A discriminant analysis using 6 biochemical variables was attempted to differentiate between PRL-negative and -positive tumours, which would be helpful in patients with borderline hyperprolactinaemia. Dopamine agonist therapy led to suppression of serum PRL with few exceptions in patients with PRL-positive and -negative tumours, whereas shrinkage was only observed in PRL-immunostainable tumours with high serum PRL levels (over 18 000 mU/l). All patients with PRL-negative tumours showed no change or even growth of the tumour despite dopamine agonist therapy. Our observations indicate that a pituitary macroadenoma associated with serum PRL of more than 3000 mU/l is most probably a prolactinoma (tumour immunostainable for PRL). Dopamine agonist therapy is effective in PRL suppression and tumour shrinkage in most of these patients. Macroadenomas without hormone hypersecretion or with borderline hyperprolactinaemia below 3000 mU/l may or may not contain PRL-immunostainable cells. Dopamine agonist therapy is effective in suppression of serum PRL also in most of these patients, but definite tumour shrinkage was not observed even in patients with PRL-immunostainable tumours of this group.
Effects of oestrogen and human growth hormone on pregnancy-associated plasma proteins in the rat
Authors: Carlsson-Bostedt L. , Frölander N. , Edén S. , Stigbrand T. , von Schoultz B.
Published: December 2008

Abstract. The serum concentrations of pregnancy-associated murine protein-1 (PAMP-1), acute phase α2macroglobulin, albumin, transferrin, and complement factor 3(C3) were followed in male rats during continuous infusions of oestradiol-17β and human growth hormone. Three different patterns of protein response could be distinguished. A distinct acute phase response without any additive influence of the given hormones was recorded for α2-macroglobulin, whereas the levels of albumin, transferrin and C3 were virtually unaffected throughout the experiment. Growth hormone gave a rapid and pronounced increase of PAMP-1 levels, whereas the response to oestradiol of this 'steroid-sensitive' protein was significantly weaker and delayed. It is suggested that the apparent oestrogenic influence on certain pregnancy-associated plasma proteins is mediated via growth hormone.
Insulin resistance following nocturnal hypoglycaemia in insulin-dependent diabetes mellitus
Authors: Kollind M. , Adamson U. , Lins P. E.
Published: December 2008

Abstract. Glucose metabolism was studied by a somatostatin-insulin-glucose infusion test (SIGIT) for 8 h in 7 male patients with insulin-dependent diabetes mellitus. They were investigated on two occasions in random order, with and without preceding hypoglycaemia induced between 3.00 and 4.00 h. SIGIT was started at 7.00 h when blood glucose was restored to normal and the counterregulatory hormones had returned to basal values. As expected, hypoglycaemia evoked an enhancement of the plasma levels of GH (43.7 ± 10.1 vs 4.4 ± 1.8 μg/l), cortisol (690 ± 59 vs 140 ± 32 nmol/l), glucagon (225 ± 35 vs 143 ± 25 ng/l), and epinephrine (3.80 ± 1.00 vs 0.10 ± 0.03 nmol/l). During the SIGIT, the levels of circulating free insulin and counterregulatory hormones were similar in the two tests notwithstanding that excessive hyperglycaemia appeared when SIGIT was preceded by hypoglycaemia. The present study thus demonstrates that nocturnal hypoglycaemia induces insulin resistance in insulin-dependent diabetic patients not deprived of insulin.
Roles of catecholamine at the preoptic region in the regulation of cyclic ovulation and gonadotropin
Authors: Hashimoto Ryuhei , Kimura Fukuko
Published: December 2008

Abstract. Experiments were designed to see how a transplantation of newborn norepinephrine (NE) neurons from A-6 groups or dopamine (DA) neurons from A-10 groups in the third ventricle at the level of the preoptic region affected the vaginal oestrous cycle and gonadotropin secretion in the female rat. Sixty-two rats that had tissues in contact with the preoptic region were evaluated as having surviving transplants by histological examination after sacrifice. The rats that had surviving NE-neuron transplants frequently showed prolongation of oestrus during the 70-day study period, indicating that ovulation was severely impaired in these rats. However, after ovariectomy, they showed a pulsatile secretion of LH with a remarkably large amplitude. The DA-neuron transplants sustained the oestrous cycle unchanged, but increased blood levels of FSH prior to the ovulatory secretion of gonadotropin. Pulsatile LH secretion was not affected. Sham and cerebellum control rats did not show any significant changes in the oestrous cycle. The results suggest that the NEneuron transplants at the preoptic region somehow inhibit gonadotropin secretion in intact rats, whereas they facilitate it in ovariectomized rats. The DA-neuron transplants appear to exert facilitatory effects on FSH secretion in intact rats.
Neuroendocrine regulation of anterior pituitary function in patients during and after molar pregnancy
Authors: Forsbach G. , Contreras J. , de Hoyos R. , Martinez-Campos A.
Published: December 2008

Abstract. Only partial studies evaluating the endocrine profile in molar pregnancy have been performed. In order to characterize the neuro-endocrine pattern during and after molar pregnancy, we studied the basal hormonal levels of hCG, human placental lactogen (hPL), FSH, GH, TSH, free thyroxine index (FTI), oestradiol-17β (E2), and progesterone (PG), as well as the anterior pituitary response to TRH, GnRH, and hypoglycaemia induced by insulin in 7 patients during molar pregnancy and one week after molar abortion. hCG showed significantly higher serum levels during rather than after molar pregnancy and hPL was detectable in only 4 patients during, but in none after molar pregnancy. FSH values were in the follicular phase range before and after molar abortion (12.7 ± 0.8 and 12.7 ± 3.5 IU/l). PRL had elevated basal levels before and after molar abortion; 103.0 ± 16.5 and 43 ± 10.6 μg/l, respectively (P < 0.05). GH levels were distinctly elevated in 3 patients during molar pregnancy; after molar abortion, the basal GH values were normal in all patients < 10 μg/l. Basal cortisol and TSH levels were in the normal range before and after molar abortion. The FTI was above the normal range in 3 patients during molar pregnancy, whereas after molar abortion the values were normalized. E2 levels were elevated before and after molar abortion, 1881 ± 477 and 96.5 ± 39.2 ng/l, respectively (P < 0.01). PG levels before and after molar abortion were 30.9 ± 5.4 and 10 ± 6.7 μg/l, respectively (P < 0.05). Comparison of women with molar pregnancy vs women with normal pregnancy showed a significant difference only as to β hCG (P < 0.05), whereas comparison of women in molar puerperium vs women in normal puerperium after term pregnancy showed a significant difference in β hCG (P < 0.01), PRL (P < 0.01), and PG (P < 0.01). Six of the 7 patients had a PRL increase of over 100% of the basal level in the first 15 min after TRH administration; one week after molar abortion, all patients had a normal PRL response to TRH. During molar pregnancy, only 3 patients showed a normal TSH response to TRH, 4 patients did not respond; 3 of them had an FTI above normal range. During the second challenge one week after molar abortion, 5 patients showed a normal TSH response to TRH. The hypoglycaemia stimulus induced a normal cortisol and GH response in 6 and in 5 patients, respectively, during molar pregnancy; after molar abortion, all patients had a normal cortisol and GH response to hypoglycaemia. FSH had no response to GnRH during or after molar pregnancy. These results establish the neuro-endocrine pattern in patients with molar pregnancy showing a clear disturbance in the neuro-endocrine regulation of the thyroid axis as well as in the GH release.
Glucoregulatory hormone response to insulin-induced hypoglycaemia following long-term calcium antagonism with felodipine in patients with essential hypertension
Authors: Katzman Per L. , Hulthén U. Lennart , Hökfelt Bernt
Published: December 2008

Abstract. The effect of 8 weeks' treatment with the dihydropyridine calcium antagonist felodipine on glucoregulatory hormone response following insulin-induced hypoglycaemia was evaluated in 7 patients with essential hypertension, WHO grade I–II. After an iv insulin injection (0.1 IU/kg), blood glucose decrement and nadir were similar before and during felodipine treatment. Basal glucagon, noradrenaline, adrenaline, GH and cortisol levels were unchanged, and the response to insulin-induced hypoglycaemia was similar before and during felodipine treatment. Basal plasma dopamine levels were similar and did not change during insulin-induced hypoglycaemia before and during felodipine treatment. Basal serum levels of TSH, T3 and T4 were unaltered following felodipine. In conclusion, long-term treatment with felodipine did not alter the hypoglycaemic effect of exogenous insulin, or the recovery from hypoglycaemia or the glucoregulatory hormone response to insulin-induced hypoglycaemia in patients with essential hypertension.
A disproportionate accumulation of fibrous tissue is not a causal factor in human goitre growth
Authors: Ramelli Fabio , Bürgi Ulrich , Siebenhüner Lotte , Kohler Heinz , Studer Hugo
Published: December 2008

Abstract. Histological preparations from human nodular goitres reveal the presence of variable and sometimes considerable amounts of acellular material separating the individual follicles. Part of this interstitial tissue consists histologically of fibrous strands. However, quantitative data on the fibrous tissue content of goitres are scarce. In the present study the proportion of fibrous tissue in normal human thyroids and human goitres was determined biochemically by measuring their content of collagen, the predominant component of fibrous tissue. Total collagen content increased in parallel to thyroid weight. The relative collagen content, however, decreased slightly but significantly with increasing thyroid weight. The collagen/DNA ratio (= fibrous tissue/cell number ratio) was not higher in goitres than in normal human thyroids. These results indicate that in goitre growth, there is no disproportionate accumulation of fibrous tissue accompanying the multiplication of thyroid follicular cells. They are in line with the earlier findings that despite histological heterogeneity, the main component of nodular goitres is newly generated follicles.
Hypertrophy and hyperplasia during goitre growth and involution in rats separate bioeffects of TSH and iodine
Authors: Stübner D. , Gärtner R. , Greil W. , Gropper K. , Brabant G. , Permanetter W. , Horn K. , Pickardt C. R.
Published: December 2008

Abstract. Goitre growth was investigated in rats receiving a low iodine diet (< 0.1 μg iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/l T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 μg T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 μg KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was a highly significant correlation between goitre weight and TSH serum level (r = 0.93, P < 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 μg KI/day (95 ± 18 μg DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 ± 21 μg DNA/gland) and under 0.5 μg KI/day (161 ± 19 μg DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.
Erythropoietin binding sites in human foetal tissues
Authors: Pekonen F. , Rosenlöf K. , Rutanen E.-M. , Fyhrquist F.
Published: December 2008

Abstract. Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has an equilibrium association constant of 4.1–6.2 × 109 1/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4–16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37°C in 1 h and at 4°C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively.
Prevalence of thyroid dysfunction in elderly subjects
Authors: Brochmann Henrik , Bjøoro Trine , Gaarder Per Ivar , Hanson Fredrik , Frey Harald M.
Published: December 2008

Abstract. The prevalence of thyroid dysfunction was investigated in a small, rural community located at the coast in Middle Norway. Two hundred persons (114 women and 86 men) of the total 802 persons over 70 years of age in the community were examined regarding thyroid dysfunction. Blood samples were drawn from 197 (113 women and 84 men). In women previously diagnosed hypothyroidism was found in 3.5% and previously diagnosed hyperthyroidism in 0.9%. In men no previously diagnosed thyroid disease was found. Undiagnosed primary hypothyroidism (TT4 < 70 nmol/l and TSH > 6 mU/l) was found in 1.8% and 1.2% of women and men, respectively. Latent hypothyroidism (TT4 70–150 nmol/l and TSH > 6 mU/l) was found in 3.5% and 2.4%, and borderline hypothyroidism (TSH 4.5–6.0 mU/l) in 3.5% and 2.4%, respectively. Undiagnosed hyperthyroidism was not found in women but in 1.2% of men. Antibody to the thyroid microsomal antigen (TMA) ≥ 400 was detected in 17.5% of women and 9.6% of men. Clearly elevated serum thyrotropin (TSH) concentrations or previously diagnosed thyroid disease were found in 21.7% and 37.5% of the TMA positive women and men, respectively.
A short water deprivation test incorporating urinary arginine vasopressin estimations for the investigation of posterior pituitary function in children
Authors: Dunger D. B. , Seckl J. R. , Grant D. B. , Yeoman L. , Lightman S. L.
Published: December 2008

Abstract. The value of a 7-h water deprivation test incorporating urinary osmolality and urinary arginine vasopressin (AVP) measurements was investigated in 20 children with suspected anterior or posterior pituitary dysfunction (group A) and 11 presenting with polyuria and polydipsia (group B). A control group of 16 healthy children was also studied. Urinary osmolalities in the control subjects after 7 h of water deprivation were 827–1136 mosmol/kg and urinary AVP 114–320 pmol/l. Of the group A patients, 5 had symptomatic diabetes insipidus with urinary osmolalities < 300 mosmol/kg, and urinary AVP concentrations of < 10 pmol/l, and 5 had normal urinary concentrating ability. The other 10 patients had varying degrees of partial diabetes insipidus (urinary AVP 6–53 pmol/l) although in 3 urinary concentrating ability was well maintained (osmolality 650–747 mosmol/kg). In group B, a diagnosis of compulsive water drinking was made in 9 patients, 1 had nephrogenic diabetes insipidus (urinary osmolality 68 mosmol/kg, AVP 782 pmol/l), and the final patient had transient diabetes insipidus. The test described was easy to perform and well tolerated even in young children. Using this test alone, it was possible to identify patients with partial defects of posterior pituitary function even when urinary concentrating ability was maintained, as well as those with complete cranial diabetes insipidus, nephrogenic diabetes insipidus, and compulsive water drinking.
Dopamine acts on acetylation of proopiomelanocortin-derived products in dog pituitary
Authors: Facchinetti F. , Perez-Fernandez R. , Toma M. O. , Gaudiero G.J. , Lechuga M.J. , Devesa J. , Genazzani A. R.
Published: December 2008

Abstract. The effect of chronic dopaminergic receptor blockade using domperidone (DOM) on the immature dog pituitary content of POMC-related peptides was evaluated. Six immature dogs were treated with DOM for 15 days, 3 times/day, po (3 mg/kg) together with DOM sc (0.6 mg/kg) at 21.00 h. Placebo was administered to six control animals with the same protocol. On the 16th day, the animals were killed, the whole pituitary removed, homogenized, and submitted to reverse-phase HPLC purification prior to radioimmunoassay (RIA) evaluation of β-endorphin, ACTH and α-MSH immunoreactivities (ir). DOM-treated dogs showed a pituitary concentration of β-EP and ACTH similar to the placebo-treated dogs. The total α-MSH ir was similar in both groups and distributed on two main peaks: one corresponding to α-MSH and another coeluting with des-acetyl-α-MSH [1-13(ACTH)NH2]. However, the percentage of α-MSH on total ir in DOMtreated dogs (15.4 ± 2.6%) was lower than in controls (37.5 ± 4.5%, P < 0.01); the corresponding percentage of 1-13(ACTH)NH2 content was 63.0 ± 3.8% vs 44.7 ± 3.7%, (P < 0.01). The α-MSH/1-13(ACTH)NH2 ratio was considerably decreased by the treatment (0.25 ± 0.06 vs 0.89 + 0.15, P < 0.01). < 0.01). Acetyl β-EP-like ir was also lower in treated (38.4 + 5.4 fmol/mg) vs control (86.6 + 19.2 fmol/mg, P < 0.05) animals. These data indicate that the dopaminergic system plays an important role in the control of acetylation processes of POMC-related peptides in the pituitary. This may be crucial as far as the biological activity of the peptides is concerned.
Inappropriate vasopressin secretion in two dogs
Authors: Rijnberk A. , Biewenga W. J. , Mol J. A.
Published: December 2008

Abstract. Two dogs with hyponatremia due to inappropriate arginine vasopressin (AVP) secretion are described. Threshold and sensitivity of AVP secretion were investigated by increasing plasma osmolality with hypertonic saline infusion. In one dog, osmoregulation of AVP secretion occurred at normal sensitivity but at a low threshold. The other dog had a relatively high plasma AVP concentration under (resting) hypotonic conditions with an otherwise normal response to increasing plasma tonicity. In the absence of evidence for associated disease, it is suggested that both dogs have an idiopathic form of the syndrome of inappropriate AVP secretion.
Growth hormone restores normal growth in selenium-treated rats without increase in circulating somatomedin C
Authors: Thorlacius-Ussing O. , Flyvbjerg A. , Jørgensen K. Damm , Ørskov H.
Published: December 2008

Abstract. Selenium intake (5.0 ppm) induces growth retardation, accumulation of selenium in somatotrophs, lack of growth hormone response to GHRH and an 80 per cent reduction in serum somatomedin C in infant rats. In addition, it induces a slight reduction in serum albumin and occasionally slight central liver necrosis. In order to determine the role of insufficient growth hormone production, the influence of exogenous growth hormone was studied during selenium intake in groups of rats during 25 to 46 days of age (post-weaning). A dosage of human growth hormone (100 μg twice daily) was chosen, this being sufficient to restore normal growth rate and normal serum somatomedin C in hypophysectomized rats of similar age. The weight gain in selenium-treated (3.3 ppm) rats was 46.0 ± 11.7 g (sd)/21 days, whereas in selenium rats given growth hormone it was 66.6 ± 8.9 g (P = 0.01), which was similar to the gain in control rats 72.3 ± 6.9 g. The latter two were less than the weight gain in control rats given growth hormone: 91.5 ± 11.5 g (P = 0.01 and P < 0.01). Serum somatomedin C in untreated rats was 151 ±66 (sd) μg/l (25 days) increasing to 532 ± 91 μg/l (34 days) and 482 ± 64 μg/l (46 days). It did not increase above these levels in control rats given growth hormone. In selenium-treated rats, no increase occurred during growth hormone administration 138 ± 148 μg/l (34 days) and 185 ± 84 μg/l (46 days) (P < 0.001 and P < 0.001 vs untreated controls). Furthermore, there was no reduction in serum protein or albumin and no liver necrosis in these selenium-treated rats. As exogenous administration of growth hormone normalizes weight gain, the results indicate that growth retardation is at least partly due to insufficient growth hormone production. The increased growth rate in seleniumtreated and control rats given growth hormone appears to be independent or circulating somatomedin C. This may be a direct effect of growth hormone or, more likely, may be caused by GH stimulation of peripheral (paracrine) formation of growth factors, possibly somatomedin C.
Thyroid function in severely traumatized patients with or without head injury
Authors: Chioléro R. L. , Lemarchand-Béraud T. , Schutz Y. , de Tribolet N. , Bayer-Berger M. , Freeman J.
Published: December 2008

Abstract. The pattern of thyroid function changes following severe trauma was assessed prospectively in 35 patients during the first 5 days after injury. Patients were divided into 2 groups to evaluate the effect of head injury: group I, patients with severe head injury; group II, patients with multiple injuries without head injury. The results demonstrate a low T3 and low T4 syndrome throughout the study, with decreases in both total and free levels of T3 and T4, normal or increased rT3 levels, and normal TSH levels. The presence of severe head injury was associated with lower levels of TSH and free T3. Mortality was 37%. Survival was associated with higher TSH and T3 levels, but not with higher T4 levels. TSH levels exceeding 1 mU/l on the first day were only observed in survivors. These findings show that a typical low T3 and low T4 syndrome is present after severe trauma in patients with multiple injury as well as with head injury. Primary hypothyroidism can be excluded, pituitary or hypothalamic hypothyroidism is likely in these patients.
Diurnal changes of plasma and cerebrospinal fluid somatostatin and 24-h growth hormone secretory pattern in man
Authors: Barreca T. , Franceschini R. , Siani C. , Perria C. , Franca viglia N. , Cataldi A. , Rolandi E.
Published: December 2008

Abstract. Somatostatin concentration was determined in plasma and in cerebrospinal fluid during a 24-h period in 7 male patients suffering from hydrocephalus of differing aetiologies. Blood and ventricular cerebrospinal fluid samples were taken every 2 h during the day (08.00–22.00 h) and every hour during the night (24.00–07.00 h). Simultaneously, plasma growth hormone levels were also evaluated. Plasma SRIH levels showed significant circadian variations with highest values in the daytime and lowest values during the night. Cerebrospinal fluid SRIH did not show any significant time-related circadian changes. Plasma GH levels showed the well-known circadian pattern in the majority of patients. No significant correlation was found between the plasma GH and plasma or cerebrospinal fluid SRIH values recorded during the 24-h period. Results suggest that peripheral SRIH does not play any major role in the control of the 24-h GH secretory pattern in man.
Recurrent attacks of vomiting, hypertension and psychotic depression: a syndrome of periodic catecholamine and prostaglandin discharge
Authors: Sato Tamotu , Igarashi Noboru , Minami Satoshi , Okabe Takashi , Hashimoto Hiroyuki , Hasui Masaki , Kato Eiji
Published: December 2008

Abstract. A syndrome of periodic catecholamine and prostaglandin E2 discharge is described in 2 patients aged 17 and 3 years. They had recurrent attacks of vomiting, hypertension and psychotic depression for several years with a fixed periodicity. At initiation of the attack, plasma ACTH, AVP, norepinephrine and prostaglandin E2 were markedly elevated, whereas dopamine was undetectable. This resulted in hypercortisolemia, hyponatremia and oliguria, which were completely normalized when the attack subsided. Dopaminergic inhibition by metoclopramide injection induced a sustained rise in plasma bicyclo-prostaglandin E2 in the patients, a transient rise in 4 controls, and no response in 8 control children. The 4 control responders had significantly higher plasma norepinephrine levels and aldosterone responses than the non-responders (P < 0.001). There was a linear correlation between peak values of bicyclo-prostaglandin E2 and basal norepinephrine levels (r = 0.990, P < 0.001). The patients released bicyclo-prostaglandin E2 and aldosterone more easily than the control responders in terms of plasma norepinephrine and dopamine levels. Treatment of the patient with clonidine was partially effective, whereas administration of indomethacin completely suppressed recurrence of the attacks for 1 year. These results suggest the etiologic possibility that the patients have a decreased dopaminergic inhibition of prostaglandin E2-mediated norepinephrine secretion, which causes periodic discharge of norepinephrine and concomitant release of ACTH and AVP.
Administration of a gonadotropin releasing hormone analogue in oligozoospermic infertile males
Authors: Badenoch D. F. , Waxman Jonathan , Boorman L. , Sidhu B. , Moore H. D. , Holt W. V. , Blandy J. P.
Published: December 2008

Abstract. This study investigated the stimulatory potential of a superactive gonadotropin releasing hormone analogue in idiopathic oligozoospermia. In a double-blind trial, 19 men were randomized to receive buserelin (D-Ser(TBU)6-GnRH ethylamide) in one of two dosages or saline, twice weekly, for twelve weeks. Treatment did not lead to a significant increase in serum concentrations of the pituitary gonadotropins or in sperm concentrations. However, in the dosages and schedules investigated, there was no inhibitory effect of the analogue. Further assessment of this approach is suggested.
Secretion of growth hormone-releasing hormone in patients with idiopathic pituitary dwarfism and acromegaly
Authors: Yamasaki Ryuichi , Saito Haruhiko , Kameyama Kazuhito , Hosoi Eiji , Saito Shiro
Published: December 2008

Abstract. The plasma levels of immunoreactive-GHRH in patients with idiopathic pituitary dwarfism and acromegaly were studied in the basal state and during various tests by a sensitive and specific RIA. The fasting plasma GHRH level in 22 patients with idiopathic pituitary dwarfism was 6.3 ± 2.3 ng/l (mean ± sd), which was significantly lower than that in normal children (9.8 ± 2.8 ng/l, N = 21), and eight of them had undetectable concentrations (less than 4.0 ng/l). Little or no response of plasma GHRH to oral administration of L-dopa was observed in 7 of 10 pituitary dwarfs, and 3 of the 7 patients showed a response of plasma GH to iv administration of GHRH (1 μg/kg). These findings suggest that one of the causes of idiopathic pituitary dwarfism is insufficient GHRH release from the hypothalamus. The fasting plasma GHRH level in 14 patients with acromegaly and one patient with gigantism was 8.0 ± 3.9 ng/l, which was slightly lower than that in normal adults (10.4 ± 4.1 ng/l, N = 72). One acromegalic patient with multiple endocrine neoplasia type I had a high level of plasma GHRH (270 ng/l) with no change in response to L-dopa and TRH test. In 3 untreated patients with acromegaly L-dopa did not induce any response of plasma GHRH in spite of inconsistent GH release, and in 4 patients with acromegaly, TRH evoked no response of plasma GHRH in spite of a marked GH release, suggesting that the GH responses are not mediated by hypothalamic GHRH. These findings suggest that the measurement of plasma GHRH in response to L-dopa with a sensitive and specific RIA could be of use in clarifying the pathophysiological role of endogenous GHRH in patients with GH secretion disorders.
Incidentally found small pituitary adenomas may have no effect on fertility
Authors: El-Hamid M. W. Abd , Joplin G. F. , Lewis P. D.
Published: December 2008

Abstract. Histological examination of the pituitary glands from 486 unselected autopsies revealed 97 clinically unsuspected adenomas in 78 glands (16%). Prolactinomas numbered 48; no hormone was found in 30, LH in 8, ACTH in 7, growth hormone (GH) and prolactin in 3, and GH alone in 1. Eleven of 194 female subjects and 37 out of 292 males had one or more prolactinoma. Clinical case notes, available for 57 of 78 subjects with adenomas, were reviewed to obtain data on fertility. Of the 25 women with case notes, 6 of the 11 with prolactinomas and 11 of the 14 with adenomas of other types had conceived. For the 32 males, 10 of the 23 with prolactinomas and 5 of the 9 with other types had procreated. These findings show that pituitary tumours not identified in life may have no major anti-fertility effect, and suggest that treatment of small intrasellar lesions discovered clinically by chance may not be necessary.
Sex difference in the relation between sellar volume and basal and GH-releasing hormone stimulated GH in acromegaly
Authors: Smals A. E. M. , Pieters G. F. F. M. , Smals A. G. H. , Kloppenborg P. W. C.
Published: December 2008

Abstract. Sellar volume and both basal (r = +0.54, P < 0.02) and GHRH-stimulated (r = +0.41, P < 0.05) GH levels were directly correlated in a group of 28 patients with acromegaly as were the latter indices (r = +0.82, P < 0.001). By subdividing the patients according to sex, a close relation between sellar size and both basal (r = +0.77, P < 0.02) and stimulated GH (r = +0.71, P < 0.02) was found only in the men, not in the women (r = +0.12 and r = +0.02, respectively, P > 0.10). The presence of a tight relation between sellar volume and basal and GHRH stimulated GH levels in male patients with acromegaly and its complete absence in women are equally intriguing and await further elucidation. A modulating role of gonadal steroids in the genesis of this sex differences remain to be assessed.
The 24-hour growth hormone secretion in a boy with giantism
Authors: Hindmarsh P.C. , Pringle P.J. , Brook C. G. D.
Published: December 2008

Abstract. The endocrinological and radiological findings in a 7.5-year-old boy with giantism are reported and compared with an age and sex matched normal tall boy. A 24-h GH profile demonstrated a persistently elevated GH concentration (mean GH concentration: giant 19.3 mU/l; tall boy 5.4 mU/l) with loss of the dominant GH periodicity of 3 h seen in the boy with tall stature and substitution with one of 8 h. These data support the view that giantism and acromegaly are similar diseases occurring prior to and following epiphyseal fusion, respectively.