bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of an oral water load and intravenous administration of isotonic glucose, hypertonic saline, mannitol and furosemide on the release of atrial natriuretic peptide in men
Authors: Yamasaki Yasuhiro , Nishiuchi Takeshi , Kojima Akihiro , Saito Haruhiko , Saito Shiro
Published: December 2008

Abstract. The effects of an oral water load and iv administration of isotonic glucose, hypertonic saline, mannitol and furosemide on release of human atrial natriuretic peptide (hANP) were examined in normal subjects to determine the main factors causing its release. In addition, the influence of age on hANP secretion was investigated. The mean plasma hANP level in normal subjects, 0–89 years old, was 20.6 ± 1.1 ng/l (mean ± sem) and showed age-related change. The plasma hANP level did not change significantly after a water load or infusion of isotonic glucose, but rose significantly from 11.4 ± 1.4 to 15.6 ± 3.2 ng/l after infusion of hypertonic saline and from 10.9 ± 1.6 to 17.8 ± 4.1 ng/l after infusion of 20% mannitol in parallel with the increase in plasma volume. The plasma hANP level decreased from 17.3 ± 2.5 to 9.0 ± 2.5 ng/l after injection of 40 mg of furosemide. A positive correlation was found between change in the plasma hANP level and percent change in the plasma volume (P < 0.001) on these treatments. The response of plasma hANP to hypertonic saline infusion was greater in older than in young men. These results indicate that 1) the secretion of hANP shows an age-related change and 2) increase in the circulating plasma volume is an important factor regulating hANP secretion.
Angiotensin II/III and substance P in human follicular fluid obtained during IVF: relation of the peptide content with follicular size
Authors: Jarry Hubertus , Meyer Bettina , Holzapfel Gerhard , Hinney Bernd , Kuhn Walter , Wuttke Wolfgang
Published: December 2008

Abstract. Ovarian follicular fluid (FF) of a number of species contain regulatory peptides secreted by granulosa cells or by autonomic nerve terminals. In this report we demonstrate the presence of authentic (HPLC-verification) angiotensin II and III as well as of substance P (SP) in human FF obtained from hMG stimulated infertile patients undergoing in vitro fertilization. Angiotensin II/III (AII/III), estradiol (E2) and progesterone concentrations increase with the size of the follicles. SP concentrations did not vary significantly in FF of various sizes. These peptide concentrations in FF are about 10-fold higher than those measured in the serum of the same patients. Attempts to correlate SP, AII/III, E2 and progesterone concentrations in the individual FF with the ability of an oocyte to be fertilized, failed. Neither AII/III, SP, E2 nor progesterone concentrations were different in these subclasses of FF. Follicles of patients punctured under general anesthesia contained significantly more SP than follicles of patients which had lumbar analgesia. AII/III concentrations were the same in FF of both treatment groups. The presence of angiotensin II and III in FF in increasing concentrations depending on the maturity of the follicle and the inability of general anesthesia to affect the AII/III concentrations suggests that this peptide is produced within the ovary.
Hormonal control of thyrotropin and growth hormone secretion in a human thyrotrope pituitary adenoma studied in vitro
Authors: Simard Marie , Mirell Carol J. , Pekary A. Eugene , Drexler Jerry , Kovacs Kalman , Hershman Jerome M.
Published: December 2008

Abstract. Pituitary thyrotrope tumours are a rare cause of hyperthyroidism. Prior in vitro studies of these tumours have revealed various patterns of differentiation and secretory activity. We have characterized the histological, biochemical, molecular and physiological features of a thyrotrope adenoma in order to define its origin and autonomy. Histochemical and electron micrograph findings confirmed the diagnosis of a thyrotrope cell adenoma. Immunostaining was positive for TSH and GH in the cytoplasm of the adenoma cells. Tissue extracts contained TSH-IR which co-eluted with authentic hTSH when analysed by gel filtration. Tumour fragments studied in a tissue culture system secreted TSH, α-subunit and GH. TRH (30 nmol/l) stimulated TSH and GH secretion. T3 (1.5 nmol/l) inhibited GH release and had no effect on TSH secretion. GnRH (50 nmol/l), dexamethasone (10−4 mol/l), SRIH (1 μmol/l) and TRH-glycine, a tetrapeptide precursor of TRH, stimulated TSH release. Dexamethasone inhibited GH and α-subunit secretion. Stable transcripts for α- and β-subunits of TSH and GH messenger RNAs were detected by molecular hybridization in cytosolic fractions. Immunohistochemistry, in vitro secretory function, and mRNA analysis suggest multidirectional differentiation of the tumour cells. TRH-glycine may have a direct stimulatory effect upon pituitary thyrotropes.
A transplantable rat Leydig cell tumour.
Authors: Erichsen Aa. , Clausen O. P. F. , Torjesen P. , Dahl E. , Wetteland P. , Hansson V.
Published: December 2008

Abstract. Growth rate and morphology were studied in a transplantable rat Leydig cell tumour (H-540) grown in intact, castrated and hypophysectomized rats. The plasma levels of pituitary hormones and testosterone were measured in the same rats. The results can be summarized as follows: 1. The growth curves of tumours in intact and castrated rats were S-shaped and very similar during the observation period of three weeks. 2. In hypophysectomized rats, the onset and progression of tumour growth were delayed, compared with intact and castrated rats. 3. The thymidine labelling index as well as the size of the S and G2 phase compartments were decreased in tumours greater than 10 g compared with smaller tumours and tumours grown in hypophysectomized rats. 4. Testosterone concentrations in plasma correlate well with increasing tumour weight up to approximately 10–15 g in intact and castrated rats. 5. Plasma testosterone levels in tumour-bearing hypophysectomized rats were 7-fold higher than those of corresponding intact and castrated rats. 6. In castrated rats, suppression of LH production occurs by very small tumours (< 2 g), whereas FSH levels show a gradual decrease with increasing tumour size. PRL production was independent of castration, tumour weight, and testosterone levels. 7. In spite of no major differences in cell morphology, the morphometric analysis revealed a reduction in tumour cell size and nuclear size in hypophysectomized rats compared with intact and castrated rats. It is concluded that pituitary hormones stimulate tumour growth, but surprisingly appear to reduce the secretion of testosterone from these tumours.
Commercially available analogues of GnRH and LH secretion
Authors: Koiter T. R. , Moes H. , Schuiling G. A.
Published: December 2008

Abstract. Six agonistic derivatives of GnRH, four of which have already been evaluated in clinical trials, were compared with GnRH itself in an in vitro test system (incubation of rat pituitary glands). It was investigated 1) how the release of LH was affected when the pituitary glands were incubated in the presence of these analogues or GnRH, and 2) how the release of LH continued after removal of the analogues or GnRH from the medium. It was also investigated how an in vivo pretreatment for 6 days with several doses of 5 of these analogues or GnRH affects 3) the plasma concentration of LH, 4) the pituitary content of LH, and, in vitro, 5) the autonomous and 6) agonist-stimulated secretion of LH. Each of the analogues showed for each of the six investigated parameters a 10- to 100-fold higher potency than GnRH itself. Between the six analogues there were only minor differences. It is discussed how the six investigated parameters may be the expression of one single property of all these analogues, namely a long retention in the pituitary gland with a strong binding to the GnRH receptor.
Evidence for a sex difference in the basal growth hormone response to GABAergic stimulation in humans
Authors: Monteleone Palmiero , Maj Mario , Iovino Michele , Steardo Luca
Published: December 2008

Abstract. Evidence has been provided supporting the existence of a sex-related difference in the GH secretion following different GH-releasing stimuli. Since pharmacological activation of the endogenous gamma-aminobutyric acid (GABA) system results in increased basal GH release in humans, the present study was undertaken to investigate whether a sex difference is present in the GH response to GABAergic stimulation. Sixteen healthy subjects (8 women and 8 men) received orally 10 mg of baclofen, the direct GABAB agonist which freely crosses the blood-brain barrier. Blood samples were collected before (T = −30 and 0) and 30, 60, 90, 120 and 180 min after the drug administration for plasma GH measurements. Following baclofen administration, plasma GH rose in healthy males (F = 19.417, P < 0.0001), but not in females (F = 1.67, NS). These results suggest that GABA modulation of human GH release is sex-dependent.
Thyroid autoantibodies in thyroid cancer: Incidence and relationship with tumour outcome
Authors: Pacini Furio , Mariotti Stefano , Formica Nunzio , Elisei Rossella , Anelli Stefano , Capotorti Enrico , Pinchera Aldo
Published: December 2008

Abstract. In the present investigation we studied serum anti-thyroglobulin and anti-thyroid microsomal autoantibodies, measured by hemagglutination technique, in 600 patients with thyroid cancer seen by us from 1975 to 1985 (mean follow-up 46 months). Positive thyroglobulin antibodies and/or microsomal antibodies were found in 138 (23%) patients (23.9% with papillary, 25% with follicular, 16.1% with anaplastic, and 4.1% with medullary thyroid carcinomas). The incidence of positive tests was similar in each decade of life (ranging between 21.9% and 27.9%), whereas in a normal sex-matched population with no evidence of thyroid disease, the frequency of positive tests was very low in young people and increased to 23% in people older than 60. In 64 patients with no evidence of residual or metastasic thyroid tissue after surgery and radioiodine, initially positive antibody titres became negative in 54.6%, decreased in 32.8%, did not change in 3.1%, and increased in 9.3%. On the contrary, antibody titres of patients with persistent disease became undetectable in 8.3%, decreased in 16.6%, remained unchanged in 25%, and increased in 50%. The clinical course of differentiated thyroid cancer was unaffected by the presence of thyroid antibodies and no difference was found in the death rate between antibody-positive and antibody-negative patients (11.5% and 13.6%, respectively). In conclusion, our data indicate that: 1) autoimmune phenomena are not an infrequent finding in thyroid cancer; 2) as in non-malignant thyroid diseases, positive-antibody tests are more frequently observed in females than in males; 3) at variance with normal controls, no age-dependent increase in serum anti-thyroid antibodies was found in thyroid cancer; 4) the presence of metastatic thyroid tissue seems to be necessary to perpetuate the autoantibody synthesis, and 5) anti-thyroid autoantibodies are not a protective or worsening factor in the tumour outcome.
Natriuretic action of arginine vasopressin in the conscious unrestrained rat
Authors: Brimble M. J. , Forsling M. L. , Musabayane C. T.
Published: December 2008

Abstract. A method for studying the renal action of AVP in the saline-infused conscious unrestrained rat is described. Conscious rats infused iv with 0.077 mol/l NaCl at 150 μl/min had a plasma AVP concentration of 0.70 ± 0.15 mol/l. AVP administration at 6 and 24 μU/min resulted in plasma AVP levels of 0.97 ± 0.14 and 2.27 ± 0.30 mU/l, respectively. AVP administration at 6 μU/min increased Na+ excretion from 11.9 ± 0.80 to 14.0 ± 0.9 μmol/min and at 24 μU/min AVP raised Na+ excretion from 10.3 ± 0.7 to 14.0 ± 1.1 μmol/min. The increases were accompanied by the expected reductions in urine flow. As the changes in plasma AVP are within the range occurring in response to moderate dehydration, the observed increases in Na+ excretion provide support for the view that AVP is involved in the physiological regulation of Na+ excretion.
Plasma concentrations of adrenocorticotropin-related peptides after corticotropin-releasing hormone and vasopressin injections in sheep
Authors: Pradier P. , Dalle M. , Tournaire C. , Delost P.
Published: December 2008

Abstract. Ovine corticotropin-releasing hormone (1 μg/kg body weight) and arginine vasopressin (1 μg/kg) were injected iv in sheep, both separately and in combination. Plasma were sampled just before and 5, 15 and 30 min after the injection. Adrenocorticotropin-related peptides were isolated by Sephadex G-50 column chromatography and measured by RIA. Cortisol and aldosterone were determined on the same plasma samples. Three molecular forms of immunoreactive ACTH (IR-ACTH) were isolated: 'big' (> 20 000 mol wt), 'intermediate' (= 8000 mol wt) and 'little' (= 4500 mol wt). Following CRH injections, the three molecular forms of ACTH were enhanced, particularly the 'little' form, whereas 'intermediate' IR-ACTH was highly and specifically responsive to AVP. After a simultaneous injection of CRH and AVP, additive increases occurred for 'intermediate' and 'little' IR-ACTH. The release of different molecular forms of IR-ACTH after stimulation by CRH or AVP of corticotrope cells suggests that ACTH-related peptides could be stored in different intracellular pools or secreted by different pituitary cells.
The effects of cytokines, antithyroidal drugs and glucocorticoids on phagocytosis by thyroid cells
Authors: Matsunaga Mayumi , Eguchi Katsumi , Fukuda Takaaki , Tezuka Hiroshi , Ueki Yukitaka , Kawabe Yojiro , Shimomura Chikako , Otsubo Toshio , Ishikawa Naofumi , Ito Kunihiko , Nagataki Shigenobu
Published: December 2008

Abstract. The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-α, -β, and -γ (IFN-α, β, and γ), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37°C for 20 h and were further incubated with fluoresceinated latex beads at 37°C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-β was consistently seen, little effect was detected with IFN-α and -γ. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.
Monoclonal antibodies against rat adrenocortical cell antigens
Authors: Laird S. M. , Vinson G. P. , Whitehouse B. J.
Published: December 2008

Abstract. Cell lines secreting antibodies directed against rat adrenocortical cell antigens have been produced using hybridoma techniques. As tested by immunofluorescent staining, eleven of these antibodies were specific for rat adrenocortical cells in that they did not interact with rat adrenal medulla, liver, muscle, ovary or kidney cells. Two of these antibodies were studied in greater detail. One interacted with an antigen present only in adrenal fasciculata and reticularis cells (inner zone antibody, IZA). The expression of the antigen with which this antibody interacted was increased by in vivo treatment with ACTH. The other antibody interacted with an antigen present in all three adrenocortical cell types (adrenocortical antibody ACA). Expression of this antigen was unaffected by ACTH treatment. The effect of both antibodies on steroid biosynthesis by mitochondrial and microsomal preparations of zona glomerulosa and inner zone tissue was tested. For these experiments, the antibodies were purified from culture media by Protein-A-Sepharose affinity chromatography. ACA had no effect on steroidogenesis by any preparation. IZA specifically decreased the production of 18-hydroxydeoxycorticosterone from deoxycorticosterone by the inner zone microsomal and mitochondrial fraction. The results suggest that the IZA antigen is found predominantly in the rat adrenal inner zone and that the antibody may be useful in monitoring adrenocortical zonation. In addition, the antigen would appear to have a functional role in steroid metabolism.
Size reduction of an ACTH-secreting pituitary macroadenoma in Nelson's syndrome by sodium valproate: effect of withdrawal and re-institution of treatment
Authors: Loli Paola , Berselli Maria Elisa , Vignati Federico , De Grandi Carlo , Tagliaferri Mariantonella
Published: December 2008

Abstract. We describe herein the reduction in the size of an ACTH-secreting pituitary macroadenoma in a patient with Nelson's syndrome during chronic administration of sodium valproate, and the changes in tumour volume after withdrawal and re-institution of treatment. The patient had elevated plasma ACTH levels (1123–1255 pmol/l), which increased markedly after CRH stimulation. A first 4-month course of sodium valproate administration (600 mg/day, orally) was started. Plasma ACTH fell to 550–726 pmol/l with persistence of responsiveness to CRH; brain computed tomography showed a clearcut reduction of tumour size. One month after drug withdrawal, the tumour volume appeared unchanged and plasma ACTH values ranged between 374 and 440 pmol/l. One and a half year after drug withdrawal, a brain computed tomography showed re-expansion of the pituitary adenoma with evidence of suprasellar extension, which had never been seen previously. Plasma ACTH ranged between 113 and 199 pmol/l. A second course of sodium valproate was started; after three months, a brain computed tomography documented clearcut reduction of tumour volume from a suprasellar extension to a partially empty pituitary fossa. Plasma ACTH ranged from 396 to 542 pmol/l with persistence of responsiveness to CRH. The present report documents for the first time the reduction of tumour size in a patient with an ACTH-secreting macroadenoma by chronic administration of sodium valproate.
Evening urinary free corticoids: a screening test in Cushing's syndrome and incidentally discovered adrenal tumours
Authors: Laudat M. H. , Billaud L. , Thomopoulos P. , Vera O. , Ylliaand A. , Luton J. P.
Published: December 2008

Abstract. In this study, we investigated the usefulness of the determination of evening urinary free corticoids/creatinine in samples collected from 20.00 to 24.00 h as a screening test in Cushing's syndrome. In controls (N = 61) the ratio values ranged from 1.1 to 9.4 μmol/mol, whereas in patients with Cushing's syndrome (N = 20), they ranged from 27.5 to 855.5 μmol/mol. However, in 28% of patients with major obesity (> 50% overweight) and no hypercortisolism, the ratio values were between 9.4 to 27.8 μmol/mol. A short (10 days) hypocaloric diet induced a decrease in the values in 75% of these patients; the normal range was reached in 50% of them. In addition, the evening urinary free corticoids/creatinine was slightly abnormal in 8 out of 10 patients with incidentally discovered 'silent' adrenal adenomas, whereas it was normal in all 6 with other adrenal masses. In conclusion, evening urinary free corticoids/creatinine is easy to obtain and it reaches a higher sensitivity (100%) and specificity (97%) than the 24 h urinary free corticoids. In the case of borderline values, the presence of overweight should be taken into account.
Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans
Authors: Mallo Charles , Zaidan Radwan , Faure André , Brun Jocelyne , Chazot Guy , Claustrat Bruno
Published: December 2008

Abstract. An oral preparation of melatonin was administered daily at 22.00 h to 6 healthy volunteers during summer on 4 consecutive days (days 1–4). The daily dose was 8 mg of melatonin as a single. Three 24-h melatonin, cortisol and prolactin profiles were determined in plasma by radioimmunological methods: 1) before treatment (day 0); 2) the first day after the 4-day treatment had been stopped (day 5), 3) the third day after withdrawal of this treatment (day 7). For the melatonin rhythm, an advanced phase was observed at day 7 vs day 0, whereas the amplitude and the mesor were not modified, whatever the day. For the prolactin profile, a significant increase as compared with the control day (day 0) was detected only at day 7 between 19.00 and 21.00 h. No modification was recorded for the plasma cortisol secretion. These results suggest that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion. This effect must be investigated over several days after the treatment has ended.
Further evidence that brain histamine H2 receptors are stimulatory in the control of prolactin in the rat
Authors: Netti Carmela , Sibilia Valeria , Guidobono Francesca , Villa Isabella , Franco Paola , Pecile Antonio
Published: December 2008

Abstract. The effects of administration into the brain ventricle of H2 receptor agonists (4-methylhistamine, 0.8 μmol/rat; dimaprit, 0.4–0.8 μmol/rat), H2 antagonists (cimetidine, 0.8 μmol/rat; ranitidine, 0.4–0.8 μmol/rat; famotidine, 0.03 μmol/rat) and of the dimaprit chemical analogue SK&F 91487 (0.4 μmol/rat) on unstimulated and histamine-stimulated prolactin secretion in normal male rats were studied. The H2 agonist 4-methylhistamine caused a significant increase in unstimulated blood PRL, whereas dimaprit, SK&F 91487, and the H2 antagonists tested did not change PRL levels. 4-Methylhistamine significantly enhanced the stimulatory effects of histamine on prolactin, whereas all the H2 antagonists inhibited histamine-induced prolactin release. The inhibition of histamine-induced prolactin secretion by the H2 agonist dimaprit is nonspecific, since its chemical analogue SK&F 91487, which has no H2 agonist activity, also inhibits it. These results indicate that stimulation of the H2 receptors in the central nervous system is facilitatory for PRL secretion, suggesting that the activation of H2 receptors may contribute to the PRL-releasing effects of histamine.
Carcinoma of the prostate with Cushing's syndrome
Authors: Fjellestad-Paulsen Anne , Abrahamsson Per-Anders , Bjartell Anders , Grino Michel , Grimelius Lars , Hedeland Hans , Falkmer Sture
Published: December 2008

Abstract. A case is described of a patient with a smallcell prostatic carcinoma containing immunoreactive CRH, in conjunction with ACTH-dependent Cushing's syndrome. The serum concentrations of CRH, ACTH, β-endorphin and calcitonin were all found to be above normal. Post-mortem examination revealed a prostatic tumour with multiple metastases, and a diffuse hyperplasia of pituitary corticotropic cells and adrenal cortical cells. In sections of the primary prostatic tumour, immunoreactive cells were demonstrable with antisera raised against human CRH, TSH, calcitonin and somatostatin, but not with antisera against ACTH or β-endorphin. By radioimmunoassay the CRH-like material could also be demonstrated in extract of the prostatic tumour and the material from both plasma and tumour extract eluted at the position of human CRH on gel chromatography (Sephadex G-75). These findings provide support for the interpretation that the patient's Cushing's syndrome was due to a CRH-producing prostatic tumour. Finally, the origin and the clinical significance of the neuroendocrine cells in the prostatic carcinoma is discussed.
Effects of glycosylation inhibitors on human growth hormone receptor in cultured human lymphocytes
Authors: Asakawa Kumiko , Hedo Jose A. , Gorden Phillip , Shizume Kazuo
Published: December 2008

Abstract. IM-9 cultured human lymphocytes were treated with N-linked glycosylation inhibitors, N-linked oligosaccharide processing inhibitors, or neuraminidase to study the effect of glycosylation modification on human growth hormone binding and molecular weight of surface hGH receptor. One mg/l tunicamycin and 20 mmol/l glucosamine decreased 125I-hGH binding to the cells to 46.3 ± 2.4% (mean ± sem) and 21.9 ± 0.2% of the controls, respectively. The hGH binding was 33.0 ± 18.4% of the control value in the cells treated with monensin. The inhibition of binding was due to a decrease in the hGH receptor number without any affinity changes in these cells. Neither 1 mg/l swainsonine nor 100 mg/l castanospermine had any effect on the hGH binding. On the other hand, 125I-hGH binding to neuraminidase-treated cells was significantly enhanced with accompanying affinity changes. When 125I-hGH was cross-linked to IM-9 cells, there were no differences in the molecular weight of hGH receptor complexes (140K) between untreated cells and cells treated with tunicamycin, glucosamine, monensin, or castanospermine. However, the 128K hGH-receptor complex appeared in swainsonine-treated cells; this complex was sensitive to endoglycosidase H. These data show that the altered carbohydrate moiety changed hGH binding and the size of surface hGH receptor and suggest that glycosylation of receptor is important for the binding of hGH and for its physiological action.
Immunocytochemical and biochemical localization of insulin-like growth factor I in the kidney of rats before and after uninephrectomy
Authors: Andersson Göran L. , Skottner Anna , Jennische Eva
Published: December 2008

Abstract. The localization of insulin-like growth factor I (IGF-I, somatomedin C) was investigated in the kidney of adult rats during normal conditions and after nephrectomy, using immunocytochemical and biochemical methods. In the normal kidney, IGF-I immunoreactivity could be demonstrated mainly in cells in the medullary collecting ducts and in those parts of the thin limb of Henle's loop located in the outer medulla. During compensatory growth all parts of the collecting ducts, including those in the cortex, showed IGF-I immunoreactivity, as did cells in the entire thin limb of Henle's loop. No IGF-I immunoreactivity could be demonstrated in the proximal or distal tubules, either in the control kidney or during compensatory growth. Biochemical measurements showed a significantly higher content of IGF-I in the inner medulla than in the cortex in the normal kidney. Uninephrectomy resulted in significantly increased IGF-I content in the cortex. It is suggested that IGF-I is produced mainly in the collecting ducts and in the thin limb of Henle's loop and exerts its effect on other parts of the nephron by paracrine mechanisms.
Genetically determined differences in newborn rat islet sensitivity to interleukin-1 in vitro: no association with the diabetes prone phenotype in the BB-rat
Authors: Andersen Henrik Ullits , Mandrup-Poulsen Thomas , Egeberg Jørn , Helqvist Steffen , Nerup Jørn
Published: December 2008

Abstract. This study was designed to investigate whether the genetic predisposition to insulin-dependent diabetes mellitus (IDDM) might be caused by an inherited increased sensitivity of the pancreatic B-cells to immune effector molecules e.g. the monokine interleukin 1 (IL-1), which is selectively cytotoxic to B-cells in vitro. Islets of Langerhans isolated from newborn diabetes prone and diabetes resistant Bio-Breeding rats, as well as from the inbred non-diabetic rat strains Wistar Furth, Brown-Norway and Lewis-Scripps were exposed to 0–1000 fg/1 of recombinant human IL-1 β for 7 days. Strain-related differences in the sensitivity to IL-1 were studied by comparing the dose-responses of insulin release at 11 mmol/l glucose and islet light microscopic morphology to varying concentrations of IL-1. Statistical analyses showed a significant impact of strain on B-cell sensitivity to IL-1, Brown-Norway islets being relatively resistant to the action of IL-1. However, the the diabetes prone islets were not more sensitive to the cytotoxic effect of IL-1 than the non-diabetic control strain islets. We conclude that genetic differences in the response to IL-1 exist in vitro, but that this phenomenon is unrelated to the propensity to develop IDDM.
Effects of repetitive administration of growth hormone-releasing hormone on growth hormone secretion, insulin-like growth factor I, and bone metabolism in postmenopausal women
Authors: Franchimont Paul , Urbain-Choffray Didier , Lambelin Pierre , Fontaine Marie-Anne , Frangin Gerard , Reginster Jean-Yves
Published: December 2008

Abstract. This study sought to determine whether GH response to synthetic GHRH was impaired in 13 postmenopausal (55-71 years) as compared with that in 8 eugonadal women and whether IGF-I and bone metabolism were consequently depressed. Thereafter, the effects of daily iv injections of 80 μg GHRH-44 for 8 days were studied in the same postmenopausal group. In addition to significantly higher basal IGF-I and osteocalcin levels (P< 0.005) in eugonadal as compared with the postmenopausal women, the administration of one GHRH-44 injection resulted in significantly higher 120-min postinjection GH maximum peak and cumulative responses in the former group as well (P< 0.005). Highly significant correlations were observed between 17β-estradiol plasma levels and either GH maximum peak or cumulative responses to GHRH-44 when both groups were pooled together, but not when considered independently. In postmenopausal women, a correlation was found between both age and duration of menopause and GH responses. Repeated GHRH-44 injections in postmenopausal women induced a significant increase in GH response (P< 0.001) as well as in IGF-I levels from day 4 to 8. No phospho-calcium parameters were modified except for a significant rise in osteocalcin from day 2 to 8. These data indicate an age-related loss of sensitivity of somatotrope cells to GHRH-44 in postmenopausal women, partly corrected by repeated daily GHRH-44 injections. As a consequence of the GHRH-induced increase in GH secretion, IGF-I was also enhanced and may be responsible for a stimulatory effect on bone formation, as shown by the osteocalcin increase, uncoupled from bone resorption.
Gonadal function and ovarian galactose metabolism in classic galactosemia
Authors: Kaufman Francine Ratner , Xu Yan Kang , Ng Won G. , Silva Paul D. , Lobo Rogerio A. , Donnell George N.
Published: December 2008

Abstract. Evaluation of ovarian steroid secretion, histologic examination of ovarian tissue, and incubation studies with radiolabelled galactose in ovarian tissue slices were performed in a 21-year-old woman with galactosemia and incipient ovarian failure. After exogenous gonadotropin administration in an attempt to achieve fertility, there was no evidence of ovulation by ultrasound; estrogen and androgen production were deficient indicating ovarian unresponsiveness. Histologic examination of the ovary revealed that the ovarian stroma had an increase in fibrous tissue and that a few hyalinized atretic follicles were present with no intermediate or evolving Graffian follicles. After incubation with galactose-l-14C, there was absence of labelled CO2 production and only labelled galactose-l-phosphate was identified as compared to controls in which several labelled intermediates could be seen. The incorporation of galactose into the TCA-insoluble fraction was drastically reduced in the patient compared to controls, suggesting that there may be a deficiency of ovarian galactose-containing glycolipids, glycoproteins and mucopolysaccharides in the galactosemic ovary. Deficiency in the production of galactose containing compounds, or galactose-phosphate accumulation or both, may lead to the development of hypergonadotropic hypogonadism seen in women with galactosemia.
Degradation of atrial natriuretic peptide in dogs
Authors: Masuda Takashi , Shichiri Masayoshi , Marumo Fumiaki
Published: December 2008

Abstract. To clarify the degradation of atrial natriuretic peptide (ANP) in dogs, plasma ANP concentrations in blood samples drawn from the coronary sinus, and in simultaneously collected blood samples of the arteries and veins of the lung, liver, kidney, spleen and cervix, and of the supramesenteric artery and the portal vein, were measured, both when infused with exogenous ANP (280 ng · kg−1 · min−1, N= 7) and when not infused (N = 6). Venous ANP concentrations in most organs showed lower values than arterial levels by 11.6 to 33.6%, suggesting degradation during circulation. Exogenous ANP infusion resulted in a 26.0 to 41.9% arterio-venous decrease in ANP levels. These findings suggest that each organ contributes to ANP degradation, and that no specific organ plays a key role. The plasma ANP concentration was not reduced when blood samples were incubated for 60 min at 37°C. The plasma from the coronary sinus and forearm vein contained essentially idential ANP molecular forms, as shown by gel permeation chromatography. Thus, the blood circulation through various organs does not cause high molecular weight ANP to be changed to other forms.
Tissue distribution and levels of gene expression of three steroid hydroxylases in ovine fetal adrenal glands
Authors: Tangalakis Kathy , Coghlan John P. , Connell John , Crawford Robert , Darling Paula , Hammond Vicki E. , Haralambidis Jim , Penschow Jenny , Wintour E. Marelyn
Published: December 2008

Abstract. Northern blotting and hybridization histochemistry were used to evaluate the ontogeny and cellular distribution of the mRNAs of the cytochrome P-450 enzymes: cholesterol side-chain cleavage (P-450scc), 17α-hydroxylase (P-45017α) and 21-hydroxylase (P-450c21) in 40 ovine fetal adrenals from 42 days of gestation until term (151 days). The genes for P-45017α and P-450scc were expressed strongly in tissue from young (40–60 days) and old fetuses (120 days to term), but to a very minor degree in 90–120 day fetuses. P-450c21 showed a steady increase throughout gestation. In the morphologically immature an unzoned adrenal of the 40-50 day fetus there was some differentiation in gene expression, all cells containing P-450scc and P-450c21 but a few lacking P-45017α. Once morphological zonation had occurred (80 days), P-45017α was confined to the fasciculata. After 120 days there was a radial maturation pattern of the fasciculata cells morphologically, adult-type cells first appearing at the medullary border. However, P-45017α and P-450scc mRNAs were equally well expressed in all sections of the fasciculata. The conclusions were: 1) the previously demonstrated triphasic cortisol biosynthetic capacity of ovine fetal adrenals was correlated with the presence, absence, and reappearance of mRNAs P-45017α and P-450scc; 2) morphological appearance of fetal adrenocortical cells and expression of three major steroidogenic enzyme genes were not correlated.
Treatment with active vitamin D (alphacalcidol) in patients with mild primary hyperparathyroidism
Authors: Lind Lars , Wengle Bo , Sørensen Ole Helmer , Wide Leif , Åkerström Göran , Ljunghall Sverker
Published: December 2008

Abstract. The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 μg alphacalcidol (1α-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no significant decrease of the PTH levels. Eighteen of the subjects thereafter entered an open study with a higher dose of alphacalcidol (2.0 μg) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D.
Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes
Authors: Hother-Nielsen Ole , Schmitz Ole , Andersen Per H. , Beck-Nielsen Henning , Pedersen Oluf
Published: December 2008

Abstract. Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 ± 1.2 vs 11.4 ± 1.2 mmol/l, P< 0.01) without enhancing mean day-time plasma insulin (43 ± 4 vs 50 ± 7 mU/l, NS) or C-peptide levels (1.26 ± 0.12 vs 1.38 ± 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 ± 0.16 vs 1.44 ± 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 ± 0.11 vs 1.38 ± 0.11 mmol/l, P< 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 ± 38 vs 313 ± 33 mg · m−2 · min−1, P< 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 ± 5.8 vs 50.6 ± 2.8 ml · n−2 · min−1,, P< 0.05), whereas basal hepatic glucose production was unchanged (81 ± 6 vs 77 ± 4 mg · m−2 · min−1, NS). Conclusions: 1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion. 2) The improved glycemic control during metformin treatment was associated with an enhanced insulin-mediated glucose utilization, presumably in skeletal muscle, whereas no effect could be demonstrated on hepatic glucose production.
Variations in the plasma concentration of atrial natriuretic factor across 24 hours
Authors: McCance David R. , Roberts Geraldine , Sheridan Brian , McKnight John A. , Leslie Hilary , Merrett J. Desmond , Atkinson A. Brew
Published: December 2008

Abstract. There is little information available concerning the presence or absence of a normal variation in the circulating concentration of atrial natriuretic homone throughout a 24 h period. We have examined this in 8 normal subjects (aged 23–35 years) on a fixed 120 mmol Na+ diet. Circulating levels of ANH, plasma renin activity, serum aldosterone and serum cortisol were determined two-hourly during 24 h in a supine position. There was a significant change in the concentration of each of these four hormones during the study period (P< 0.05). ANH: peak 8.5 (22.00 h), nadir 4.0 (12.00 h) (pmol/l); PRA: peak 1.7 (04.00 h), nadir 0.8 (22.00 h) (μg · l−1 · h−1); aldosterone: peak 350 (14.00 h), nadir 143 (22.00 h) (pmol/l); cortisol: peak 346 (08.00 h), nadir 51 (22.00 h) (nmol/l). Peak plasma ANH occurred at 22.00 h and with the exception of times 20.00 h and 10.00 h this value was significantly higher than all the other time means (P< 0.05). The only other significant differences were between plasma ANH at 20.00 h and 06.00 h, 08.00 h, 12.00 h and 14.00 h, respectively (P< 0.05). From midnight until 18.00 h, there was no significant difference between any of the time means. There was a peak in PRA at 04.00 h, while peak serum aldosterone and serum cortisol occurred at 14.00 h and 08.00 h, respectively. This study suggests that ANH may display a diurnal rhythm. Our findings provide further physiological evidence that plasma ANH and PRA may have a reciprocal relationship.
Changes in the bioactivity to immunoreactivity ratio of circulating luteinizing hormone in impotent men treated with testosterone undecanoate
Authors: Carani C. , Celani M. F. , Zini D. , Baldini A. , Casa L. Della , Marrama P.
Published: December 2008

Abstract. Testosterone undecanoate was administered orally (80 mg twice daily) for 30 days to 10 impotent men with mild Leydig cell failure, age 28 to 42 years. Placebo was administered for 30 days both before and at the end of testosterone undecanoate therapy. Serum levels of bioactive LH, immunoreactive LH and testosterone were determined in basal conditions (day zero), 30 days after the first placebo administration, at the 15th and 30th day of testosterone undecanoate therapy, and at the end of the second treatment with placebo (90th day). Bioactive LH was measured by a sensitive and specific in vitro bioassay based on testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH and testosterone were determined by a doubleantibody RIA technique. The results were compared with those obtained in 30 untreated normal young men. In the basal state, serum concentrations of immunoreactive LH were significantly higher in the patients (P< 0.02) than in control subjects, whereas testosterone levels were significantly lower (P< 0.001) in the impotent men. In contrast, bioactive LH levels and the bioactive LH to immunoreactive LH ratios were similar in the two groups. In the patients, at the 15th day of treatment with testosterone undecanoate, serum levels of testosterone and bioactive LH were significantly higher (P< 0.01) than basal values, whereas immunoreactive LH concentrations showed no significant changes. Consequently, the bioactive LH to immunoreactive LH ratios rose significantly (P< 0.01). At the 30th day of treatment with testosterone undecanoate, the mean value of bioactive LH and the mean bioactive LH to immunoreactive LH ratio were significantly higher (P< 0.01) in the patients than in control men, whereas the mean levels of testosterone and immunoreactive LH were similar in the two groups. Neither the first nor the second treatment with placebo changed the hormone values observed in basal conditions. The results support the experimental evidence that androgens may increase the bioactivity of circulating LH.
Effect of hypophysectomy on the growth and development of the sheep adrenal gland: a morphometric study
Authors: Coulter C. L. , Young I. R. , Browne C. A. , McMillen I. C.
Published: December 2008

Abstract. We have investigated the effect of gestational age and fetal hypophysectomy on the growth and development of the adrenal gland of the fetal sheep. The area of the fetal sheep adrenal medulla increased significantly (P< 0.05) from 3.21 ± 0.42 mm2 at 90–107 days to 6.09 ± 0.26 mm2 at 120-126 days of gestation and there was a further significant increase (P< 0.05) in the newborn period to 9.48 ± 0.85 mm2. The adrenomedullary area of the hypophysectomised fetal sheep (7.47 ± 1.10 mm2) was not significantly different from that of the fetal sheep at 140–146 days of gestation or from that of the newborn lamb. The ratio of the area of the adrenal occupied by the cells which contained adrenaline (adrenaline zone) to the area of the adrenal occupied by the cells which contained noradrenaline (noradrenaline zone) was unchanged between 90 days of gestation and 12 days after birth. After hypophysectomy, the ratio of the adrenaline to noradrenaline zone was not significantly different from that in the adrenal medulla of the 140–146 days fetal sheep and the 10–12 days newborn lamb.
Influence of diet on the development of antral gastrin-like immunoreactivity in the stomach of rats
Authors: Okahata Hiroyasu , Nishi Yoshikazu , Muraki Kotaro , Arai Masaru , Kubo Norio , Sumii Koji , Miyachi Yukitaka , Ueda Kazuhiro
Published: December 2008

Abstract. The effects of individual food constituents on antral gastrin-like immunoreactivity concentrations were studied in young rats. Rats aged 7 to 20 days were given only rat breast milk and then weaned by various nutrients (regular laboratory chow, protein (ovalbumin)-, fat- or carbohydrate (starch)-rich food). Rats receiving rat breast milk only until 27 days of age were also studied. In rats on regular laboratory chow, antral gastrin-like immunoreactivity increased and reached adult levels on day 25. In rats on ovalbumin, fat-rich food or starch, it increased on day 23 but dropped thereafter. The increment by laboratory chow was higher than that by the individual nutrients. No increase was observed during milk feeding alone. Gel filtration of antral gastrin-like immunoreactivity from 25-day-old rats on laboratory chow or three essential nutrients showed the same results.
Reduction of serum gonadotropin concentrations after parathyroidectomy
Authors: Kristoffersson Anders , Grankvist Kjell , Järhult Johannes
Published: December 2008

Abstract. Calcium, parathyroid hormone, folliclestimulating hormone, luteinizing hormone, and estradiol were measured in 15 postmenopausal women with primary hyperparathyroidism before and 1 year after parathyroidectomy. Normalization of serum calcium concentrations (from 2.87 to 2.29 mmol/l) was followed by a highly significant fall in serum LH and FSH concentrations. No significant alteration occurred in plasma estradiol concentration.
The corticotropin-releasing hormone test in normal short children: comparison of plasma adrenocorticotropin and cortisol responses to human corticotropin-releasing hormone and insulin-induced hypoglycemia
Authors: Goji Katsumi
Published: December 2008

Abstract. The human corticotropin-releasing hormone (hCRH) tests were performed in twelve normal short children, and the responses of plasma ACTH and cortisol to iv administration of 1 μg/kg hCRH were compared with those to insulin-induced hypoglycemia. After administration of hCRH, the mean plasma ACTH level rose from a basal value of 3.3 ± 0.4 pmol/l (mean ± sem) to a peak value of 9.2 ± 0.8 pmol/l at 30 min, and the mean plasma cortisol level rose from a basal value of 231 ± 25 nmol/l to a peak value of 546 ± 30 nmol/l at 30 min. The ACTH response after insulin-induced hypoglycemia was greater than that after hCRH administration; the mean peak level (P < 0.01), the percent maximum increment (P < 0.01), and the area under the ACTH response curve (P < 0.01) were all significantly greater after insulin-induced hypoglycemia than those after hCRH administration. Although the mean peak cortisol level after insulin-induced hypoglycemia was about 1.3-fold higher than that after hCRH administration (P < 0.01), neither the percent maximum increment in plasma cortisol nor the area under the cortisol response curve after insulin-induced hypoglycemia was significantly different from that after hCRH administration. Consequently, the acute increases in plasma ACTH after the administration of 1 μg/kg hCRH stimulated the adrenal gland to almost the same cortisol response as that obtained with a much greater increase in plasma ACTH after insulin-induced hypoglycemia. These results suggest that a plasma ACTH peak of 9–11 pmol/l produces near maximum acute stimulation of adrenal steroidgenesis.