bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of a luteinizing hormone-releasing hormone antagonist on experimental endometriosis in the rat
Authors: Jones Robert C.
Published: December 2008

Abstract. The effect of a Salk LRH analogue (Antagonist I) on growth of endometrial explants in the intact female rat was studied. Subcutaneous injection of the analogue was begun 3 weeks after transplantation of a section of endometrium to the peritoneal wall. The animals were laparotomized and the volume of the explant (length × width × height) in mm was measured with calipers on day 1 of treatment. The animals were injected daily for 3 weeks with 50, 250 or 500 μg of Antagonist I at which time the animals were again laporatomized and the volume of the explant measured. Eight weeks after cessation of treatment the animals were sacrificed and the volume of the explant measured. The degree of inhibition of explant growth was directly correlated with the amount of Antagonist I administered; a significant inhibition was obtained with doses of 250 or 500 μg. Eight weeks after cessation of treatment all explants demonstrated renewed growth, although explants in rats which had been treated with 250 or 500 μg had returned to only 51 and 61% of their initial volume, respectively. The results of this study demonstrate the LRH antagonists may be useful in the treatment of endometriosis although at doses considerably higher than those of the super agonists.
Effects of systemic and local administration of etomidate on adrenocortical steroidogenesis in male rats
Authors: Jarry H. , Dietrich M. , Düker E. , Wuttke W.
Published: December 2008

Abstract. A method for focal dialysis of the adrenal cortex is introduced allowing determination of adrenal steroid local release rates in conscious, freely moving rats. Etomidate, an anaesthetic drug known to interfere with adrenal steroid synthesis, blocks not only corticosterone but also aldosterone and, to a lesser degree, progesterone release. Intra-adrenal application of the drug via the dialysis system for a defined time resulted in low release rates of corticosterone without inducing sedation of the animals or even anaesthesia. Remaining low steroid concentrations during the next 5 h after cessation of the dialysis with drug-containing medium indicate that the inhibition of steroid synthesis lasted for several hours. It is concluded that the inhibitory effect of etomidate on steroid biosynthesis can be explained on the basis of an interaction of the drug with adrenocortical enzymes without the involvement of hypothalamic or hypophyseal mechanisms.
Further observations on the autoregulation of the prolactin receptor in rat ventral prostate explants
Authors: Rui H. , Brekke I. , Torjesen P. A. , Purvis K.
Published: December 2008

Abstract. In confirmation and extension of an earlier preliminary communication, ovine prolactin was found to elevate prolactin binding by approximately 100% in rat ventral prostate explants incubated for 20 h in vitro. A stimulation was observed with low doses of ovine hormone (150 μg/l) which, from available data on the relative biological potencies, could be considered equivalent to the upper limit of the physiological range of endogenous rat prolactin. The response was associated with a lag period of 3–6 h. The effect could be obtained with other lactogenic hormones, including human and rat prolactin and human growth hormone, but not with non-lactogenic hormones such as insulin, hCG, corticosterone, testosterone or oestradiol. The prostaglandin synthesis inhibitor, indomethacin, and the Ca2+-antagonist, verapamil, could not counteract the increase in prolactin binding induced by prolactin treatment, nor could dibutyryl cyclic AMP alone mimic the response. These data suggest that prostaglandins, Ca2+ or cAMP do not mediate the alteration in receptor binding. Furthermore, inhibition of lysosome activity by chloroquine could not alone increase the prolactin binding in the control tissues, suggesting that up-regulation does not simply reflect a protective action of prolactin on receptor degradation.
Preproenkephalin B-derived opioid peptides in human phaeochromocytomas
Authors: Yanase Toshihiko , Nawata Hajime , Kato Ken-ichi , Ibayashi Hiroshi
Published: December 2008

Abstract. We demonstrated the presence and the secretion in vivo and in vitro of immunoreactive preproenkephalin B-derived opioid peptides (α-neoendorphin, dynorphin and leumorphin) in human phaeochromocytomas. In senventeen human phaeochromocytomas and two human adrenal medullas, the tissue contents of immunoreactive preproenkephalin B-derived opioid peptides (α-neoendorphin, dynorphin and leumorphin) and leu-enkephalin were studied by specific RIAs. Compared with a remarkable wide distribution in amounts of immunoreactive leu-enkephalin (1063 ± 437 pg/mg, mean ± se), small amounts of immunnoreactive α-neoendorphin (22.6 ± 6.4 pg/mg) and dynorphin (8.5 ± 1.2 pg/mg) were detected in all seventeen human phaeochromocytomas and the two human adrenal medullas. Leumorphin-like immunoreactivity was detected in only four tumours. Gel chromatographic studies revealed the presence of preproenkephalin B-derived peptides and their high molecular forms. A significant positive correlation between the tumour tissue contents of immunoreactive α-neoendorphin and of dynorphin was observed. Nicotine (10−5, 10−4 mol/l) significantly stimulated the secretion of immunoreactive α-neoendorphin and dynorphin as well as leuenkephalin and catecholamines from cultured human phaeochromocytoma cells. Administration of 1 mg of glucagon to a patient with medullary phaeochromocytoma induced a rapid increase in the plasma concentration of immunoreactive α-neoendorphin with a concomitant increase in plasma catecholamines. These results indicate the presence of preproenkephalin B-derived opioid peptides in human phaeochromocytomas and human adrenal medullas and their secretion in human phaeochromocytomas.
Glucocorticoid modulation of growth hormone secretion in vitro. Evidence for a biphasic effect on GH-releasing hormone mediated release
Authors: Ceda Gian Paolo , Davis Robert G. , Hoffman Andrew R.
Published: December 2008

Abstract. Glucocorticoids have been shown to have both stimulatory and suppressive effects on GH secretion in vitro and in vivo. In order to study the kinetics of glucocorticoid action on the somatotrope, cultured rat pituitary cells were exposed to dexamethasone for varying periods of time. During short-term incubations (≤ 4 h), dexamethasone inhibited GHRH and forskolin-elicited GH secretion, but during longer incubation periods, the glucocorticoid enhanced both basal and GHRH-stimulated GH release. The inhibitory effect of brief dexamethasone exposure was also seen in cells which previously had been exposed to dexamethasone. In addition, growth hormone secretion from cultured rat and human somatotropinoma cells was inhibited by a brief exposure to dexamethasone. Thus, the nature of glucocorticoid action on the isolated cultured somatotrope is biphasic, with brief exposure inhibiting, and more prolonged exposure stimulating GH secretion.
Statural development parallels IGFI levels in subjects of constitutionally variant stature
Authors: Binoux Michel , Gourmelen Micheline
Published: December 2008

Abstract. Using a protein-binding assay which measures mainly IGF I, serum levels of insulin-like growth factor (IGF) were determined in 263 children and adolescents of constitutionally variant stature but with normal GH secretion following provocative stimuli. A positive correlation was found between height age and the logarithm of IGF levels (r = 0.67, P < 0.001). Furthermore, a correlation was found in the tall and short subjects as a group between the ratio of IGF/normal IGF for age and between the ratio of growth rate/normal growth rate for age (r = 0.53, P < 0.001). Subjects were compared at the same stage of development. At a given bone age or stage of puberty, tall subjects had significantly higher IGF levels than short subjects (P < 0.005). After the completion of growth, IGF levels in both short and tall subjects stabilized within the normal range. Nevertheless, their mean levels remained significantly different (P < 0.001). Our results suggest that in normal children and adolescents, differences in IGF I secretion may be at least partially responsible for the individual differences in growth.
Release of glucagon-like peptide 1 immunoreactivity from the perfused rat pancreas
Authors: Shima Kenji , Hirota Meisei , Ohboshi Chizuko , Sato Mitsuyo , Nishino Tomoyoshi
Published: December 2008

Abstract. A reliable radioimmunoassay for glucagon-like peptide 1 (GLP-1) was developed with a detection limit of 12 pmol/l, which enabled us to detect the subtle change in concentrations of this peptide in the perfusate from the perfused rat pancreas. With this RIA, GLP-1 immunoreactivity (GLP-1 IR) was found to be secreted synchronously with glucagon immunoreactivity upon arginine stimulation from the perfused rat pancreas. Gel chromatographic analysis showed the presence of GLP-1 IR in the pancreatic extract which is eluted at the same position as synthetic GLP-1 (1-37). Moreover HPLC analysis confirmed the presence of GLP-1 IR, which eluted at exactly the same position as synthetic GLP-1, in the perfusate from pancreas perfusion upon stimulation of arginine. These results suggest that the pancreas stores and secretes GLP-1 IR concomitantly with glucagon as one of the cleavage products of their common precursor.
Serum free thyroid hormones in different degrees of hypothyroidism and in euthyroid autoimmune thyroiditis
Authors: Ferrari C. , Paracchi A. , Parisio E. , Codecasa F. , Mucci M. , Boghen M. , Gerevini G. , Rampini P.
Published: December 2008

Abstract. Serum total and free T4 and T3, thyroxinebinding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 μg, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism. Nevertheless, the finding that both FT4 and FT3 are in the normal range in some patients with mild and in most with subclinical hypothyroidism indicates that increased TSH secretion remains the most sensitive index of thyroid failure.
Glucokinase in pancreatic B-cells and its inhibition by alloxan
Authors: Lenzen Sigurd , Tiedge Markus , Panten Uwe
Published: December 2008

Abstract. Characterization of glucokinase in pancreatic B-cells from ob/ob mice and from rat liver revealed identical characteristics. A narrow substrate specificity; high Km values for the two substrates, D-glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody. These characteristics distinguish glucokinase in soluble cytoplasmic fractions of pancreatic B-cells and liver from low Km hexokinases. Alloxan is a pancreatic B-cell cytotoxic agent, which has been widely used as a tool for the elucidation of the mechanisms of insulin secretion, because its inhibitory action on insulin secretion has been presumed to be intimately related to the mechanism of glucose-induced insulin secretion. Alloxan inhibited glucokinase but not hexokinase activity in cytoplasmic fractions of pancreatic B-cells and liver. The half maximal inhibitory concentration of alloxan was 5 μmol/l. Glucokinase activity was protected from alloxan toxicity only by D-glucose and D-mannose; the α anomer of D-glucose provided significantly greater protection than the β anomer. The non-metabolizable sugar 3-0-methyl-D-glucose did not provide protection of glucokinase activity against inhibition by alloxan. Thus, inhibition of pancreatic B-cell glucokinase may contribute to the inhibition of glucose-induced insulin secretion by alloxan. These results support the contention that glucokinase regulates the metabolic flux rate through the glycolytic chain in the pancreatic B-cell and thereby generates the signal for glucose-induced insulin secretion.
Effect of transport stress on luteinizing hormone released by GnRH in dairy cows
Authors: Dobson Hilary
Published: December 2008

Abstract. Stress is thought to reduce gonadotrophin secretion in ruminants. So far, only prolonged administration of ACTH or cortisol have been shown experimentally to reduce LH release. The present experiment studied the effects of an acutely stressful situation. Fifteen min after the start of a 30 min truck journey for dairy cows plasma cortisol values exceeded 55 nmol/l, as measured by RIA. Values began to decline 15–45 min after return to the barn and reached baseline (2.5 to 20 nmol/l) 1–2 h later. Responses to 20 or 40 μg GnRH administered on day 10 of the cycle, or 48 h after prostaglandin analogue, were significantly reduced on a within-animal basis when given during the truck journey. Hence acute endogenous stimulation of pituitary-adrenal activity can interfere with pituitary LH release.
Elevated anti-α-galactosyl antibody titres. A marker of progression in autoimmune thyroid disorders and in endocrine ophthalmopathy?
Authors: Etienne-Decerf J. , Malaise M. , Mahieu P. , Winand R.
Published: December 2008

Abstract. The titres of anti-α-galactosyl antibodies were measured by passive haemagglutination in 50 control subjects and in 128 patients presenting with various thyroid disorders. Titres of control subjects ranged from 1/10 to 1/80, regardless of age and blood group. Elevated titres (> 1/80) were constantly noted in 6/6 patients with progressive exophthalmos, in 5/5 patients with untreated Graves' disease, and in 11/12 patients with progressive nontoxic goitre. By contrast, the titres were within the normal range in primary myxoedema (17 patients) and in residual exophthalmos (11 patients), whereas they were only erratically increased in 1/31 patients with treated or cured Graves' disease and in 5/36 patients with nonprogressive nontoxic goitre. Finally, elevated titres were also found in 3/7 patients presenting with autoimmune thyroiditis. No correlations could be established between elevated titres and the thyrotropin binding inhibiting immunoglobulin activity, the antithyroglobulin antibody titres or the antimicrosomal antibody titres. As in the control subjects, the anti-α-galactosyl antibodies mainly belonged to the IgG class. Affinity purified anti-α-galactosyl antibodies were capable of binding to trypsinized human and porcine thyroid cells in culture, as shown by indirect immunofluorescence. On the other hand, they were not able to react with untreated thyroid cells. The data show that the measurement of anti-α-galactosyl antibody titres could represent an easy and useful tool to determine whether an autoimmune thyroid disorder is in progression. Besides, they suggest that some of the antigenic determinants implicated in the enhanced production of anti-α-galactosyl antibodies are present, but normally hidden, within the cell surface of thyroid cells.
Effect of sham-feeding on glucose tolerance and insulin secretion
Authors: Lorentzen M. , Madsbad S. , Kehlet H. , Tronier B.
Published: December 2008

Abstract. Glucose, 25 g, was infused iv with or without sham-feeding in seven normal males. Sham-feeding improved glucose tolerance, incremental area of blood glucose being 63% (P < 0.05) of that during iv glucose without sham-feeding. The actual insulin secretion evaluated from the total area under the C-peptide and insulin curves did not differ during iv glucose with or without sham-feeding. These results suggest that the cephalic-vagal reflex improves glucose tolerance during iv glucose, independent of changes in β-cell function.
Erythrocyte metabolism in hyperthyroidism:
Authors: Monti M. , Hedner P. , Ikomi-Kumm J. , Valdemarsson S.
Published: December 2008

Abstract. Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 ± 2 mW/l erythrocytes which was higher than the post-treatment value of 99 ± 2 (P < 0.001) as well as the value for 14 euthyroid subjects, 108 ± 2 mW/l (P < 0.001). The NaF inhibitable rate was 73 ± ± before and 63 ± 1 mW/l after therapy (P < 0.01). These values correspond to 61 ± 1 and 64 ± 1% (n.s.) of the total heat production rate, and were similar to that of 61 ± 2% for the controls. Heat production rates in the presence of NaF were 47 ± 1 before and 36 ± 1 mW/l after therapy (P < 0.001), representing 39 ± 1 and 36 ± 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.
Glucose, β adrenergic effects, and pancreatic endocrine function in the isolated perfused duck pancreas
Authors: Gross R. , Mialhe P.
Published: December 2008

Abstract. Duck isolated perfused pancreas was used to assess glucose, adrenergic mediated effects and pancreatic function interrelationships. A moderate physiological 50% increase in glucose level, corresponding closely to the difference observed between 24-h-fasted and fed animals, induced a significant decrease of pancreatic glucagon not due to a rise in somatostatin secretion. The great responsiveness of the A cell was still found after glucagon stimulation by catecholamines or β adrenergic agonism. Insulin was irresponsive to the glucose load we used, suggesting that glucose-induced glucagon suppression was also insulin independent. As far as the D cell was concerned, glucose had no effect on pancreatic somatostatin output; however, an interesting finding was that β adrenergic agonism has a permissive effect on D cell responsiveness to the nutriment.
Renal handling of thyroxine, 3,5,3'- and 3,3',5'-triiodothyronine, 3,3'- and 3',5'-diiodothyronine in man
Authors: Faber Jens , Siersbæk-Nielsen Kaj , Kirkegaard Carsten
Published: December 2008

Abstract. The 24-h urinary excretion and renal clearance of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 3',5'-diiodothyronine (3',5'-T2) were measured in 17 healthy subjects. The median urinary excretion was (pmol/24h) T4: 1242, T3: 828, rT3: 12.9, 3,3'-T2: 331, and 3',5'-T2: 5.8. The corresponding renal clearances were in median (ml/min) T4: 31, T3: 133, rT3: 15, 3,3'-T2: 683, and 3',5'-T2: 4.5. The clearances differed mutually (P < 0.01) as well as from the creatinine clearance (P < 0.01) which was in median 87 ml/min. Thus, all iodothyronines studied were subject to tubular transport mechanisms besides glomerular filtration. The 3 iodothyronines with 2 iodine atoms in the phenolic ring of the thyronine molecule, T4, rT3 and 3',5'-T2, were mainly tubularly reabsorbed, whereas those with only one iodine atom in the phenolic ring, T3 and 3,3'-T2, were mainly tubularly secreted. It might be hypothesized that the number of iodine atoms in the phenolic ring determines the direction of the tubular transport (presence of 2 iodine atoms is associated with tubular reabsorption, and of one iodine atom with secretion), whereas the rate of tubular transport decreases with decreasing number of iodine atoms in the tyrosylic ring.
Primary role of glucagon release in the effect of β-endorphin on glucose homeostasis in normal man
Authors: Paolisso Giuseppe , Giugliano Dario , Scheen André J. , Franchimont Paul , D'Onofrio Felice , Lefèbvre Pierre J.
Published: December 2008

Abstract. The present study aimed at evaluating the effect of human β-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h β-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 ± 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 ± 13 ng/1). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of β-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, β-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between β-endorphin and control studies. We conclude that the naturally occurring opioid peptide β-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of β-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism.
Substance P stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro with involvement of oestrogen
Authors: Ohtsuka Shirou , Miyake Akira , Nishizaki Takamichi , Tasaka Keiichi , Aono Toshihiro , Tanizawa Osamu
Published: December 2008

Abstract. The effects of substance P on the release of LH and GnRH were examined in a sequential double-chamber perifusion system by perifusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in dioestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats were perifused in series with substance P (10−6 mol/l), the concentration of LH in the efflux was significantly (P < 0.05) increased by 70– 120% compared with that before the injection, but substance P had no effect on LH release from the pituitary perifused alone. This LH release by substance P increased in a dose-dependent manner and was blocked by substance P antagonist. Administration of 10−6 mol/l substance P induced a significant release (40–80% increase, P < 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10−6 mol/l substance P induced significant release (50–100% increase, P < 0.05) of LH and GnRH in ovariectomized rats with an implanted oestradiol capsule, but caused no significant increase in LH release in ovariectomized rats without an oestradiol capsule. Progesterone injection to both ovariectomized rats and ovariectomized rats with an implanted oestradiol capsule had no significant effect on the response of LH to substance P. These findings suggest that substance P induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that oestrogen may be involved in these processes.
Cerebrospinal fluid dynorphin 1-17 and β-endorphin in late pregnancy and six months after delivery
Authors: Lyrenäs Sven , Nyberg Fred , Lutsch Helen , Lindberg Bo , Terenius Lars
Published: December 2008

Abstract. Cerebrospinal fluid (CSF) levels of dynorphin A and β-endorphin were measured by radioimmunoassay in 62 primiparae in term pregnancy before onset of labour. In 50 of these women acupuncture (AP) treatment was given in an antenatal preparation procedure. In 15 of the AP-treated women, CSF samples were further obtained six months after delivery. Median values for dynorphin A were 7.5 pmol/l in AP-treated women and 6.4 pmol/l in non-treated controls. The puerperal median value for dynorphin A was 7.6 pmol/l. Median values for β-endorphin were 7.1 pmol/l in AP-treated women and 5.7 pmol/l in non-treated controls. The median β-endorphin value after delivery was 7.3 pmol/l. There was no significant difference in CSF dynorphin A or β-endorphin levels between the AP-treated women and non-treated controls in late pregnancy. Consequently, the present study does not support the theory of a positive influence on either the dynorphin or the β-endorphin system by manual AP. Within subject comparisons of dynorphin-A and β-endorphin failed to indicate any significant trend in samples obtained in late pregnancy and 6 months after delivery, and there was no increased activity in either the dynorphin or the β-endorphin system in late pregnancy, as reflected by CSF levels.
Effects of high-dose ketoconazole and dexamethasone on ACTH-stimulated adrenal steroidogenesis in orchiectomized prostatic cancer patients
Authors: De Coster R. , Mahler C. , Denis L. , Coene M. C. , Caers I. , Amery W. , Haelterman C. , Beerens D.
Published: December 2008

Abstract. The effects of high-dose ketoconazole (i.e. 400 mg every 8 h) therapy on adrenal steroidogenesis were investigated in 7 patients with advanced prostatic cancer who no longer responded to orchiectomy. An ACTH challenge was performed before and on days 14 and 28 of high-dose ketoconazole treatment. During the last 14 days, dexamethasone (0.5 mg twice daily) was administered together with ketoconazole. High-dose ketoconazole alone lowered the basal levels of the androgens by 49–66%. It almost completely inhibited their stimulation by ACTH, whereas plasma progesterone was doubled. Basal cortisol was only slightly lowered, but the response to ACTH stimulation was markedly blunted. Basal and stimulated plasma aldosterone remained unaffected. Both basal and stimulated 11-deoxycortisol, 11-deoxycorticosterone, and, to a lesser extent, corticosterone rose more markedly after ketoconazole than after placebo. The basal and stimulated plasma adrenal androgen levels were further reduced after combined ketoconazole-dexamethasone treatment, whereas plasma corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone were lowered in the same way as cortisol. Aldosterone and progesterone profiles were similar to those observed under high-dose ketoconazole, but plasma 17α-hydroxyprogesterone increased more markedly than after high-dose ketoconazole alone. These results demonstrate that high-dose ketoconazole lowers plasma androgen levels in orchi-ectomized patients and partly inhibits the gluco- and mineralocorticoid syntheses, especially after ACTH-stimulation. The addition of dexamethasone does not only correct the possible consequence of the impairment of the cortisol production by high-dose ketoconazole, but it further reduces the androgen levels and lowers the plasma concentrations of most precursors, for instance 11-deoxycorticosterone, which has some physiological mineralocorticoid activity. Therefore, a systematic combined therapy may be recommended, when high-dose ketoconazole treatment is given to patients with metastatic prostate cancer.
Effects of the three neuropeptides, vasoactive intestinal peptide, substance P, and calcitonin gene related peptide on basal and stimulated calcitonin release in the rat
Authors: Månsson B. , Ahrén B. , Nobin A.
Published: December 2008

Abstract. Calcitonin is secreted from the thyroidal C-cells. Except that calcitonin secretion is stimulated by calcium, little is known of its regulation. Vasoactive intestinal peptide (VIP), substance P, and calcitonin gene related peptide (CGRP) have recently been detected within intrathyroidal neurons, and CGRP also within the C-cells, and may therefore affect calcitonin secretion. In this study, we investigated whether VIP, substance P or CGRP could influence calcitonin secretion in the rat. Each of these peptides was administered as a single injection (1.5 nmol/animal) or as a 30-min infusion (1.5 nmol/animal per 30 min) during which calcium chloride, 456 μmol/animal, was injected iv. We found that the peptides had no effect on basal calcitonin secretion, but that VIP potentiated the calcium-induced calcitonin release. Thus, the peak plasma calcitonin level following calcium chloride injection was doubled by the infusion of VIP (P < 0.001). In contrast, neither substance P nor CGRP significantly influenced the calcium-induced calcitonin release. We conclude that VIP, a neuropeptide within intrathyroidal nerves, has the capacity to augment calcium-induced calcitonin secretion in the rat and we therefore suggest that VIP is a regulator of calcitonin secretion.
Long-term effect of 90Y pituitary implantation in acromegaly
Authors: Jadresic A. , Jimenez L. E. , Joplin G. F.
Published: December 2008

Abstract. This report examines the long-term trends in GH levels and pituitary function in a group of 38 acromegalic patients who were selected insofar as we were able to follow them up for more than 10 years after a single dose of 90Y interstitial pituitary irradiation as the sole treatment. Mean serum GH had fallen from 106 to 24 mIU/l within 3–6 months and then slowly declined to 4 mIU/l after 10 years. GH levels of ≤ 5 mIU/l during a 50 g oral glucose tolerance test were obtained in 8% of patients at 3–6 months and in 18% at 1 year, the cumulative percentage increasing to 53% at 10, and 76% at 14 years. The percentage of patients requiring hormone replacement therapy rose from nil pre-implant to 16% by 3–6 months, and then slowly increased to 39% by 14 years. Serial coned radiographs of the pituitary fossa were available for 32 patients. By 10 years, 16 showed thickening of the dorsum sellae and/or reduction of at least one diameter by 3 mm. Concerning symptoms, all 29 patients whose GH level fell to ≤ 5 mIU/l showed improvements, 22 becoming asymptomatic. Seven patients with lesser falls in GH levels (from a mean of 193 to a mean of 15 mIU/l) all improved, one becoming asymptomatic. Two showed no variation. These results show that 90Y pituitary implants have a cumulative effect over the years in inducing remission and hypopituitarism in acromegalic patients, the early decline in GH levels being swifter than from other forms of irradiation.
Central diabetes insipidus in children.
Authors: Fjellestad-Paulsen Anne , Tubiana-Rufi Nadia , Harris Alan , Czernichow Paul
Published: December 2008

Abstract. The antidiuretic effect and pharmacokinetics of 10 to 20 μg of intranasal (IN) and 200 to 400 μg of oral (po) 1-deamino-8-D-arginine vasopressin (DDAVP) were studied in 10 paediatric diabetes insipidus patients. A significant increase in urine osmolality was obtained with all doses, maximum within 2 h and still present at 8 h. At 12 h after administration, the ratio urine osmolality/plasma osmolality was above 1 only after 20 μg intranasally and 400 μg perorally. The free water clearance decreased rapidly with all doses and was similar in magnitude and duration for both the intranasal and peroral routes of administration and remained negative for more than 8 h. The maximum plasma concentrations of DDAVP, measured with a specific and sensitive RIA method, was dose-dependent and there was not significant difference in time until maximum concentration was obtained or in plasma half-life between the two routes of administration. The ratio established, 1:20, by calculating the area under the curve showed a bio-equivalence between 10 μg IN and 200 μg po and between 20 μg IN and 400 μg po of DDAVP. This work further emphasized the effectiveness of the oral route and the rapidity of absorption. By continuous monitoring of DDAVP plasma values we have demonstrated that peak values were reached within one hour after administration. This study demonstrates that the doses needed to treat diabetes insipidus patients by the oral route will be approximately 20 times greater than by the nasal route.
Continuous insulin infusion therapy and retinopathy in patients with type I diabetes
Authors: Helve Eero , Laatikainen Leila , Merenmies Lauri , Koivisto Veikko A.
Published: December 2008

Abstract. The effect of continuous subcutaneous insulin infusion (CSII) and conventional injection therapy (CIT) on retinopathy was evaluated in a 1-year crossover study (6 + 6 months) with 54 type I diabetic patients. The glycaemic control improved significantly but did not reach euglycaemic levels during CSII (P < 0.01–0.001), whereas no change was observed during CIT. At baseline, 50% of the patients had no retinopathy, 20% had only minimal changes, 26% had moderate background retinopathy, and 2 patients had proliferative changes. During CSII, the retinopathy grade impaired in 7 patients, whereas no deterioration occurred during CIT. Improvement of retinopathy grading was observed in 2 patients during CSII and in 5 during CIT, respectively. Individual retinal lesions also progressed more and improved less during CSII (12:3) as compared with CIT (10:9). The net impairment in both retinopathy grading and individual lesions was significant during CSII as compared with CIT (P < 0.05). There was no difference in the baseline characteristics (severity of retinopathy, age, sex, duration of diabetes, insulin dose, blood pressure, serum creatinine), in the fall of glycosylated haemoglobin or number of hypoglycaemic episodes between the patients with and without worsening of retinopathy during CSII. The present study suggests that even a moderate improvement in metabolic control induced by CSII may be associated with a risk of progression of retinopathy during the first months of therapy.
Naloxone administration does not affect gonadotropin secretion in patients with Klinefelter's syndrome
Authors: Forti G. , De Feo M. L. , Maggi M. , Genazzani A. D. , Fazzi V. , Delitala G.
Published: December 2008

Abstract. Plasma LH and FSH were measured every 20 min in a group of patients with Klinefelter's syndrome before and after placebo or naloxone administration (8 mg iv as a bolus followed by an infusion of 4 mg/h for 4 h) both in baseline conditions (N = 6) and during treatment with testosterone enanthate (200 mg im every two weeks; N = 4). The mean LH areas measured during saline infusion in baseline conditions (7888 ± 758 IU/l per min mean ± sem) and during testosterone treatment (5042 ± 2039 IU/l per min) were not significantly different from those measured during naloxone infusion (baseline 8317 ± 818 IU/l per min; during testosterone treatment 5395 ± 2007 IU/l per min). Similar results were obtained for FSH. These data suggest that in patients with Klinefelter's syndrome, the opioidergic inhibition of gonadotropin release is lacking and is not restored by testosterone replacement therapy.
Changes in collagen and elastin of the rat aorta induced by experimental diabetes and food restriction
Authors: Andreassen Troels T. , Oxlund Hans
Published: December 2008

Abstract. The biochemical and biomechanical properties of aortas from diabetic rats were investigated after a period of three months. Diabetes caused increased non-enzymatic glycosylation of lysine and hydroxylysine residues of collagen, whereas no changes were found in the reducible collagen cross-links. Although diabetes caused a reduction in the thickness of the aortic wall and a decrease in the dry weight and amount of collagen and elastin per mm2, no changes were found in the mechanical strength and stiffness of the wall. When the mechanical parameters were corrected for the decrease in dry weight, the tensile strength of the aortic wall was found to be increased compared with the control group. This increase in the stability of aortic collagen can be explained by formation of reactive carbonyl compounds from the glycosyl-lysines, resulting in stabile cross-links between the collagen molecules.
Endocrine investigations in two cases of feminizing Leydig cell tumour
Authors: Valensi P. , Coussieu C. , Kemeny J. L. , Attali J. R. , Amouroux J. , Sebaoun J.
Published: December 2008

Abstract. Two patients, aged 32 and 35 years, presented with gynaecomastia and a unilateral testicular tumour which proved to be a Leydig cell tumour. Pre-operative samples taken at 08.00 h on different days showed marked elevation of plasma oestradiol in the first patient, and very slight irregular oestradiol elevation in the second, plasma oestrone within the normal range in both patients, reduced plasma testosterone in the first patient and reduced or normal testosterone in the second, and low or low-normal serum LH and FSH in both patients. One of the patients received an oral dose of 100 mg of clomiphene citrate for 3 consecutive days which induced a rise in LH and FSH and a decrease in the 17-hydroxyprogesterone/androstenedione ratio. These data suggest the inhibiting effect of endogenous hyperoestrogenism on testicular steroidogenesis owing to both the reduction of gonadotropin secretion and a direct local negative effect on C 17,20-lyase. After human chorionic gonadotropin stimulation, oestradiol response was increased and abnormally prolonged, a finding which may be helpful when diagnosing a feminizing Leydig cell tumour; testosterone reached normal values. After removal of the tumoural testis, gynaecomastia regressed within a few days, gonadotropins increased, oestrogens dropped, testosterone and 5α-dihydrotestosterone normalized in one patient but remained low in the other at day 30. The Leydig cells outside the tumour appeared morphologically normal, but the count gave evidence of juxtatumoural Leydig cell hyperplasia in areas where the tumour was well encapsulated while showing a significant reduction at a distance from the tumour and in the contralateral testis by comparison with control testes. An incubation procedure with [3H]testosterone was performed in one patient and showed an aromatase activity 21 times greater in the tumour than in normal peritumoural tissue, whereas the Leydig cell number per field and the percentage of the volume occupied by Leydig cells were 11 and 35 times higher, respectively. This shows that the aromatase activity of a single tumour cell is very similar to that of a normal Leydig cell.
Are Leydig cells of neural origin? Substance P-like immunoreactivity in human testicular tissue
Authors: Schulze Wolfgang , Davidoff Michail S. , Holstein Adolf-Friedrich
Published: December 2008

Abstract. Using the immunocytochemical peroxidase-antiperoxidase method we observed strong and selective staining of Leydig cells after incubation of human testicular tissue with an antiserum against substance P and a slightly weaker immunoreactivity against methionine-enkephalin. These results indicate that the embryologic origin of Leydig cells may require reconsideration and also offer a new perspective for research upon the local control mechanisms of spermatogenesis.
Effect of vitamin D2 and vitamin D3 on the serum concentrations of 1,25(OH)2D2, and 1,25(OH)2D3 in normal subjects
Authors: Hartwell Dorthe , Hassager Christian , Christiansen Claus
Published: December 2008

Abstract. Serum concentrations of vitamin D2 and vitamin D3 metabolites were measured in 19 normal subjects before and during treatment with either vitamin D2 or vitamin D3, 4000 IU per day for 8 weeks. Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. During treatment with vitamin D3, the serum concentration of 1,25(OH)2D metabolites was unchanged. We conclude that the production of 1,25(OH)2D is tightly regulated and that 1α-hydroxylase does not discriminate between D2 and D3 metabolites in normal subjects.
Differential effect of desglycinamide9-(Arg8)-vasopressin on cognitive functions of diabetes insipidus and alcoholic patients
Authors: Laczi Ferenc , László Ferenc A. , Kovács Gábor L. , Telegdy Gyula , Szász Anna , Szilárd János , van Ree Jan M. , de Wied David
Published: December 2008

Abstract. Intranasal treatment with desglycinamide9-(Arg8)-vasopressin (DGAVP) improved certain aspects of cognitive functions of patients with acquired and congenital diabetes insipidus and of alcoholic patients with mild cognitive impairments. Patients with Korsakoff's syndrome, presenting with severe cognitive impairments, were resistent to DGVP treatment. DGAVP treatment did not affect blood pressure and water metabolism. The action of DGAVP on cognitive functions is probably mediated by centrally located target sites and may be expressed only in patients in whom these target sites are unimpaired.
Testicular growth and hormonal parameters in the male Snell dwarf mouse
Authors: Hochereau-de Reviers M. T. , de Reviers M. M. , Monet-Kuntz C. , Perreau C. , Fontaine I. , Viguier-Martinez M. C.
Published: December 2008

Abstract. Dwarf mice show delayed testicular growth and their adult testis weights are half the normal value. The aims of the present work were firstly, to compare the developmental profiles of plasma gonadotropins and of testicular cell multiplication and differentiation in dwarf vs normal mice and secondly, to determine the effect of hMG supplementation on dwarf mice. In the dwarf mice no pubertal rise in plasma FSH was observed, and the adult values remained very low when compared with those of normal mice; plasma LH decreased after 40 days of age and remained equal to half the normal values. In adults, testicular testosterone content was greatly increased in dwarf mice compared with normal mice, whereas plasma testosterone and accessory gland weights were reduced. At 24 days of age, the total numbers per testis of Leydig and Sertoli cells were reduced in dwarf vs normal mice, whereas in adult mice their differentiation, but not their total numbers, was reduced. This resulted in lower daily production of leptotene primary spermatocytes and of round spermatids in dwarf than in normal mice. hMG supplementation promoted Leydig and Sertoli cell multiplication, but did not produce full differentiation, resulting in increased daily production of round spermatids. In conclusion, in adult dwarf mice a deficiency in plasma gonadotropins prevents full differentiation of Leydig and Sertoli cells without affecting the number of these cells.
Sleep-electroencephalography and the secretion of cortisol and growth hormone in normal controls
Authors: Steiger A. , Herth T. , Holsboer F.
Published: December 2008

Abstract. Sleep-electroencephalography, and the nocturnal secretion of cortisol and GH were investigated simultaneously in a sample of 25 male normal controls (27.1 ± 1.3 years) in order further to examine interaction between sleep structure and concurrent endocrine activity. Slow wave sleep activity was increased during the first part of the night, whereas cortisol concentration was low and GH output reached maximal levels. The second half of the night was characterized by a relative preponderance of REM-sleep, low GH-concentration, and an increase in cortisol. However, no distinct reciprocal interaction between cortisol and GH concentration was noted. In all subjects, a pronounced GH surge between 22.00 and 02.00 h was recorded which occurred independently of the presence of slow wave sleep. Six out of the 25 subjects showed nocturnal GH increases even before sleep onset. These data indicate that somatotropic cell activity during night is less dependent upon the sleeping state or specific conventially defined sleep stages than originally reported.
Atrial natriuretic polypeptide during exercise in healthy man
Authors: Saito Yoshihiko , Nakao Kazuwa , Sugawara Akira , Nishimura Kazunobu , Sakamoto Makoto , Morii Narito , Yamada Takayuki , Itoh Hiroshi , Shiono Shozo , Kuriyama Takanobu , Hirai Masashi , Ohi Motoharu , Ban Toshihiko , Imura Hiroo
Published: December 2008

Abstract. The plasma concentration of atrial natriuretic polypeptide was measured in eight healthy men during two grades of exercise performed in the supine position on a bicycle ergometer. The plasma concentration of atrial natriuretic polypeptide slightly increased during the first exercise test with 20% of the maximal oxygen uptake and it approximately doubled during the second exercise with 40% of the maximal oxygen uptake (from 15.5 ± 5.5 (mean ± sd) pmol/l to 31.8 ± 10.7 pmol/l). The increase in the plasma level of atrial natriuretic polypeptide in the second exercise was significantly greater than that in the first one. The plasma norepinephrine level and plasma renin activity showed significant increases during the second exercise test. Heart rate and systolic blood pressure also increased in response to the graded exercise. The increase in the plasma concentration of atrial natriuretic polypeptide during exercise was significantly correlated with the increase in heart rate, systolic blood pressure, and the plasma norepinephrine concentration (r = 0.75, r = 0.71 and r = 0.51, respectively). These results indicate that the plasma concentration of atrial natriuretic polypeptide increases in response to the intensity of a workload, and suggest that exercise is a useful test to evaluate the releasing function of atrial natriuretic polypeptide in the heart.
Reversibility of deficient sleep entrained growth hormone secretion in a boy with achondroplasia and obstructive sleep apnea
Authors: Goldstein Steven J. , Wu Richard H. K. , Thorpy Michael J. , Shprintzen Robert J. , Marion Robert E. , Saenger Paul
Published: December 2008

Abstract. Obstructive sleep apnea may lead to disordered sleep architecture and impair the physiologic slow wave sleep related growth hormone release. Obstructive sleep apnea occurs with craniofacial syndromes and in children with airway narrowing, pharyngeal hypoplasia, tonsillar adenoidal hypertrophy, micrognathia and achondroplasia. To examine the relationship between disordered sleep and growth hormone release we studied a 9 year old male with achondroplasia, growth failure (3 cm/year) and obstructive sleep apnea. Polysomnography data and a 20 min sampling for sleep entrained growth hormone showed before therapeutic tracheostomy numerous apneic episodes, absent slow wave sleep and abnormal low growth hormone secretion during sleep. Normalized slow wave sleep entrained growth hormone secretion after tracheostomy led to a sustained increase in growth rate. Normal growth rate (> 5 cm/year) continues 2 years after tracheostomy. We conclude that obstructive sleep apnea may impair sleep related growth hormone release. Obstructive sleep apnea may be a useful model for other diseases in which growth failure and sleep disturbances are linked.