bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulsatile GnRH treatment of the ovariectomized rat and release of LH and FSH
Authors: Lambalk C. B. , van Rees G. P. , Schomaker J. , de Koning J. , van Dieten J. A. M. J.
Published: December 2008

Abstract. The effect of pulsatile GnRH administration on the levels of LH and FSH was investigated in rats that had been ovariectomized 2 weeks earlier. Also the asynchronous occurrence of endogenous and GnRH-induced LH and FSH pulses was analysed. A small pulse dose of GnRH (1.25 ng/100 g) was given iv at a frequency of once every 60 min or once every 120 min during 24 h. A larger dose of 5 ng/100 g was given once every 60 or 120 min during either 24 h or 96 h. Blood was sampled arterially every 5 min around the two first and last GnRH injections and LH and FSH were measured. Only the treatment with the larger GnRH pulse dose resulted in a change of LH and FSH plasma levels. LH levels declined under all circumstances, whereas FSH was found to be increased temporarily after 24 h of treatment. The pituitary LH response to pulses of GnRH (5 ng/100 g) decreased irrespective of the frequency or duration with which GnRH was administered. There was a marked asynchronicity between LH and FSH pulses and almost every injection of GnRH (5 ng/100 g) resulted in clear LH pulses but not in FSH pulses.
Effect of insulin on basal pancreaticoduodenal output of somatostatin in normal and diabetic dogs
Authors: Ribes G. , Gross R. , Chenon D. , Loubatières-Mariani M. M.
Published: December 2008

Abstract. The effect of insulin on basal pancreaticoduodenal output of SRIH was investigated in vivo and compared in normal and alloxan diabetic dogs. The experiments were performed on anesthetized dogs having a T-shaped catheter inserted into the pancreaticoduodenal vein just at the exit of the pancreas for blood sampling. In normal dogs, an insulin infusion (1 IU/kg for 20 min) or an iv insulin injection (0.2 IU/kg over 30 sec) produced, before any change in glycemia, an immediate reduction of the venous pancreaticoduodenal output of SRIH. Then pancreaticoduodenal output of SRIH rose close to starting values and decreased again when blood glucose level became very low. In alloxandiabetic dogs, insulin infusion (1 IU/kg for 20 min) also induced an immediate inhibitory effect on pancreaticoduodenal SRIH output; the effect was more transient and from 20 min, unlike in normal dogs, an increase in pancreaticoduodenal output of SRIH was observed. In conclusion, exogenous insulin induces an immediate reduction in pancreaticoduodenal SRIH secretion both in normal and diabetic dogs, independently of basal blood glucose level and before any change in glycemia. In contrast, the delayed effect is different: SRIH secretion is reduced in normal dogs, whereas it is enhanced in diabetic dogs.
Specific and weight loss-associated effects of one-week exposure to ethanol on pituitary-gonadal function of male rats
Authors: Salonen Iiris , Huhtaniemi Ilpo
Published: December 2008

Abstract. We studied the effects of one-week ethanol exposure (2.2 g/kg twice daily) on pituitary-gonadal functions of male rats. Because ethanol decreases the food-intake of the animals, diet-restricted rats were used as controls. Testicular LH and PRL receptors of ethanol-treated rats were significantly (P <0.05–0.01) reduced in comparison with weight-matched controls. In contrast, testicular GnRH receptors of the ethanol group were increased (P <0.05). Testicular FSH binding, pituitary GnRH-receptors, and serum gonadotropins and testosterone were not affected by ethanol. The present results demonstrate a specific effect of ethanol on testicular LH and PRL receptors which, unlike some other endocrine changes during ethanol expoure, is not due to a concomitant weight loss. In addition, the results suggest a concurrent change in the putative testicular GnRH receptor associated paracrine regulation, as implied by increased testicular GnRH binding upon ethanol exposure.
Nocturnal urinary growth hormone excretion in children with short stature
Authors: Hattori Naoki , Shimatsu Akira , Yamanaka Chutaro , Momoi Toru , Imura Hiroo
Published: December 2008

Abstract. Nocturnal urinary growth hormone levels in children with short and normal stature were measured by a sensitive enzyme immunoassay. Urinary GH excretion during sleep correlated positively with peak plasma GH values during pharmacological (r = 0.74, P < 0.001) and sleep (r = 0.85, P < 0.001) tests. The amounts of urinary GH excretion during sleep differed significantly from each other in the following groups: complete GH deficiency (mean ± sem: 0.1 ± 0.1 ng/m2 of body surface area; range: < 0.1–0.4), partial GH deficiency (1.6 ± 0.3 ng/m2; 0.2–3.1), and short stature without GH deficiency (3.7 ± 0.6 ng/m2; 0.7–11.5). No significant difference was found between short stature without GH deficiency and normal stature (5.0 ± 0.5 ng/m2; 2.1 – 10.5). Measurement of nocturnal urinary GH excretion is a simple method for screening of GH excretion and may be helpful in the differentiation of the various etiologies of short stature in children.
Biosynthesis and secretion of Iutropin in rat gonadotropes treated with swainsonine
Authors: Hattori Masa-aki , Ozawa Kazunori , Wakabayashi Katsumi
Published: December 2008

Abstract. Biosynthesis and secretion of LH were investigated using primary cultures of rat gonadotropes following exposure to swainsonine, an inhibitor of N-linked oligosaccharide processing. The inhibition of terminal glycosylation by swainsonine was assessed by the increase in incorporation of [3H]mannose and the decrease of incorporation of [3H]galactose into the trichloroacetic acid-insoluble and anti-ovine LHβ immunoprecipitable fractions. This inhibitor led to an increase in cellular LH with high affinity for concanavalin A and a decrease of LH with less affinity for the lectin, although the cellular LH was not decreased. The swainsonine-treated cells accumulated highly basic LH (pI, 9.6, 10.0) in a time-dependent manner. Although the treated cells showed a decrease in the responsiveness to hormonal stimulation, there were no differenes in the rate and extent of LH secretion induced by maximal stimulation with 100 nmol/I GnRH between the control and treated cells over 24 h. The accumulation of highly basic LH molecules did not result from a decrease in their secretion, since they were secreted in the presence and absence of GnRH. It is concluded that significant changes in N-linked oligosaccharide structure of LH have no effect upon its secretion.
The role of zinc status in altered cardiac adenylate cyclase activity in diabetic rats
Authors: Mooradian Arshag D. , Morley John E. , Scarpace Philip J.
Published: December 2008

Abstract. Zinc deficiency and altered myocardial adenylate cyclase activity commonly occur in diabetes. To determine whether the zinc intake of the animal can account for the altered β-adrenergic receptor activity in the diabetic heart, we determined the β-adrenergic receptor number and isoproterenol-, NaF- and forskolin-stimulated adenylate cyclase activity in diabetic and control rats maintained on low, normal and high zinc diets for 3 weeks. Scatchard analysis of [125I]iodocyanopindolol binding to control heart membrane preparations revealed a binding capacity of 17.3 ± 1.3 fmol/mg protein with a Kd of 35 ± 1.0 pmol/l. Neither the diabetic state nor the zinc status altered these binding parameters. The isoproterenol-stimulated adenylate cyclase acticity was significantly lower in diabetic rats on low zinc diets compared with controls. The NaF- (65.1 ± 5.4 vs 60.8 ± 6.4 pmol cAMP·mg protein−1·min−1) and forskolin-stimulated adenylate cyclase activities (161 ± 9.3 vs 154 ± 21.2 pmol cAMP·mg protein−1· min−1) were not significantly altered in diabetic rats. Low dietary zinc intake compared with high zinc diet significantly increased NaF- and forskolin-stimulated adenylate cyclase activity both in diabetic rats and controls. The effect of dietary zinc content on isoproterenol-stimulated adenylate cyclase was significant in control rats only. Thus zinc intake appears to be an important determinant of cardiac adenylate cyclase activity level. Additional factors peculiar to the diabetic state are involved in the modulation of β-adrenergic responsiveness of the diabetic heart.
Effects of α-human atrial natriuretic polypeptide, sodium nitroprusside and dibutyryl cyclic GMP on aldosterone production in bovine zona glomerulosa cells
Authors: Okamoto Mitsuhiro
Published: December 2008

Abstract. When bovine adrenal zona glomerulosa cells were incubated with α-human atrial natriuretic polypeptide (α-hANP), the basal aldosterone production in the cells was hardly affected, although the angiotensin II- or K+-stimulated production was completely inhibited. α-hANP was found to cause the generation of cyclic GMP in the cells. When the cells were incubated with sodium nitroprusside, the drug inhibited the angiotensin II- or K+-stimulated aldosterone production, and also generated cyclic GMP in the cells. In contrast, dibutyryl cyclic GMP was found to be a stimulator of the aldosterone response rather than an inhibitor. The results obtained in this study cast doubt on the role of cyclic GMP as an intracellular second messenger for the action of ANP on aldosterone secretion.
Metabolic regulation of the growth hormone independent insulin-like growth factor binding protein in human plasma
Authors: Yeoh Swee Inn , Baxter Robert C.
Published: December 2008

Abstract. This study examines the regulation of circulating GH-independent insulin-like growth factor binding protein, BP-28. Commencing at 22.00 h, BP-28 in 5 normal adults rose 11-fold to peak values of 120 ± 12 μg/l, remained elevated betwen 01.00 and 08.00 h, then fell rapidly following a meal. If meals were omitted, BP-28 remained at peak levels throughout the day. The fasting BP-28 level was higher in women (141 ± 22 μg/l, N = 5) than men (59 ± 14 μg/l, N = 7), and pregnancy caused a further 2-fold elevation. Oral glucose rapidly lowered BP-28 in diabetic and nondiabetic pregnant women, non-pregnant women, and men. In a heterogeneous group of 18 subjects, insulin (0.1 U/kg iv), with or without simultaneous administratioin of GnRH and TRH, elicited a 3- to 4-fold rise in BP-28, commencing 60 min after the nadir of plasma glucose, and independent of the response in GH, PRL, TSH, LH or cortisol. We conclude that BP-28 levels in adults are metabolically regulated, and postulate a role for this protein in the maintenance of glucose homeostasis.
Effect of norfloxacin, a new quinolone, on GABA modulation of TRH-induced TSH release from perifused rat pituitaries
Authors: Roussel Jean-Paul , Tapia-Arancibia Lucia , Jourdan Jacques , Astier Hélène
Published: December 2008

Abstract. The effect of the quinolone norfloxacin, a new antibacterial agent that is thought to induce convulsions in patients by inhibiting the binding of GABA, was tested on the two kinds of GABA A modulation of fTRH-induced TSH release from perifused rat pituitaries. Norfloxacin (50 μmol/l) was found to reverse the inhibitory effect of GABA (100 nmol/l) on the TSH release induced by TRH (10 nmol/l). The ratio of induced over spontaneous release was 0.79 ± 0.05 in the presence of GABA, and 2.32 ± 0.18 when norfloxacin was added 15 min before GABA vs 2.59 ± 0.09 in the control response to TRH. Norfloxacin was also able to reverse the potentiating effect of GABA (10 nmol/l): the TSH response was 6.56 ± 0.94 in the presence of GABA alone vs 2.92 ± 0.35 with norfloxacin plus GABA. Norfloxacin was also able to reverse the potentiation induced by isoguvacine, a specific GABA A agonist (6.15 ± 1.14 in the presence of isoguvacine vs 2.99 ± 0.54 with norfloxacin plus isoguvacine). Our results suggest that norfloxacin may antagonize the effect of GABA via the two classes of GABA A receptor sites which differ in affinity and are responsible for the dual effect of GABA on the TRH-induced TSH secretion.
Triiodothyronine and 3′,5′-cyclic AMP secretion by cultured human thyroid cells in response to thyrotropin and thyroid-stimulating immunoglobulin
Authors: Kraiem Z. , Sadeh O. , Sobel E.
Published: December 2008

Abstract. We have established a relatively simple and sensitive system for measuring T3 as well as cAMP secretion using cryopreserved human thyroid cells in culture. We defined optimal culture conditions and characterized the system. T3 secretion from human thyrocytes (only 1 × 105 cells/well) could be stimulated in a time- and dose-dependent fashion by both TSH (doses as low as 10 mU/l) and thyroid-stimulating immunoglobulin to levels 5- to 10-fold above baseline. The response to the thyroid stimulating agents was preserved for at least 3 weeks. Experiments with inhibitors of iodothyronine synthesis (propylthiouracil and methimazole) indicated that the bulk of the TSH-stimulated T3 secretion measured apparently derives from de novo iodothyronine biosynthesis rather than preformed T3. We utilized the system to investigate some aspects in the regulation of human thyrocyte T3 and cAMP secretion. Maximum stimulation of the thyroid hormone was achieved at TSH doses capable of evoking a further rise in levels of cAMP. A rise in cAMP accumulation was observed as early as 15 min following exposure to TSH, whereas it took 1–4 days to detect a significant increase in T3 secretion. Within 6 h of incubation, the bulk of TSH-stimulated intracellular cAMP was found released into the medium. l-methyl-3-isobutylxanthine (MIX) caused a dose-related decrease (beyond 0.1 mmol/l MIX) in TSH-stimulated T3 secretion which contrasted with a concomitant expected increase in cAMP accumulation. Hence, as also observed in adrenal and testicular tissue, xanthines at high concentration seem to exhibit a dual action: potentiation of cAMP accumulation by inhibiting phosphodiesterase activity and a concomitant reduction of hormone formation.
Cytoendocrinological findings in the pituitary glands of patients with psoriasis
Authors: Weber G. , Heitz Ph. U.
Published: December 2008

Abstract. Twelve pituitary glands from patients suffering from psoriasis obtained at postmortem showed in all cases hyperplasia of human growth hormone-producing cells. These results support the postulated pathomechanism that psoriasis lesions may arise as a result of an increased production of human growth hormone.
17-β-estradiol treatment maintains differentiative potential of virgin mouse mammary gland in culture and its responsiveness to insulin
Authors: Komura Hiroko , Fukui Hideto , Wakimoto Hiroshi , Miyake Tetsuo , Terakawa Naoki , Tanizawa Osamu , Matsumoto Keishi , Terada Nobuyuki
Published: December 2008

Abstract. Synthesis of the milk proteins, casein and α-lactalbumin was not induced in cultured mammary explants from C3H/HeN castrated virgin mice in the presence of lactogenic hormones such as insulin, cortisol and PRL. Replacement therapy with 17-β-estradiol to the castrated mice completely restored the differentiative potentials of mammary explants, inducing synthesis of the two milk proteins. [3H] thymidine incorporation into DNA synthesized in cultured mammary explants was also decreased by castration to less than 50% (P< 0.001) of that obtained in intact mice, and 17-β-estradiol treatment to castrated animals restored DNA synthesis to 90% of the intact level. The addition of insulin to culture medium significantly (P< 0.001) enhanced [3H] thymidine incorporation into DNA in cultured mammary explants from both intact and 17-β-estradiol-treated castrated mice but not from castrated animals. Insulin binding sites (1710 ± 260 sites/cell) to mammary epithelial cells from castrated mice were significantly (P<0.05) lower than those from both intact (2870 ± 300 sites/cell) and 17-β-estradiol-treated castrated animals (2860 ± 190 sites/cell). The present findings suggest that 17-β-estradiol maintains growth and differentiative responses of mammary epithelial cells to insulin, which may be through preserving the number of insulin binding sites in the cells.
Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours
Authors: Lamberts S. W.J. , Pieters G. F. F. M. , Metselaar H.J. , Ong G. L. , Tan H. S. , Reubi J.-C.
Published: December 2008

Abstract. Two patients with metastatic endocrine pancreatic tumours initially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with an insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased initially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200–300 μg SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 μg SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initially well to SMS 201-995 treatment with 300 μg per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analogue to maximally 600 μg/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. Conclusions: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.
Identification of vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate secretion of antidiuretic hormone and an oat cell carcinoma
Authors: Smitz Simon , Legros Jean-Jacques , Franchimont Paul , Maire Marc le
Published: December 2008

Abstract. In this study we have identified and characterized several vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion and oat cell carcinoma of the lung. Immunoreactive plasma vasopressin was measured after gel filtration (Sephadex G-25) or C-18 cartridge extraction using two different region-specific antisera: AS1 and AS2. Antiserum AS1 is more specifically directed towards the antigenic site of the hexapeptidic ring of arginine-vasopressin (AVP), whereas AS2 is more specifically directed towards the C-terminal region of AVP. Unexpectedly, the Sephadex G-25 gel filtration elution profile of the immunoreactive vasopressin was very heterogeneous, indicating the presence of several molecular species. After extraction of total AVP and AVP-like peptides of this plasma, an unusual AS1/AS2 ratio of immunoreactivity was observed, suggesting the presence of vasopressin-like peptides which differ from AVP in the C-terminus.
The metabolic clearance rate, serum half-time and apparent distribution space of authentic biosynthetic human growth hormone in growth hormone-deficient patients
Authors: Jørgensen J. O. L. , Flyvbjerg A. , Christiansen J. S.
Published: December 2008

Abstract. We studied the metabolic clearance rate (MCR) serum half-time (t½) and apparent distribution space (DS) of unlabelled, authentic, biosynthetic human growth hormone (B-hGH) in 9 GH-deficient patients by means of the constant iv infusion to equilibrium technique. B-hGH was infused for 3 h at a rate of 33 ng · kg−1 · min−1 after which the disappearance from serum of GH was followed for 1 h. The mean ± sem values for MCR, t½ and DS were: 2.3 ± 0.6 ml · kg−1 · min−1, 21.1 ± 1.7 min and 67.6 ± 14.6 ml/kg, respectively. The disappearance of GH was monoexponential for the first 30 min, during which 75% of the GH had been cleared. The disappearance rate during the last 30 min of the observation period was somewhat lower, still approximately 90% of the GH had been eliminated after 60 min.
Comparison of maternal to fetal transfer of 3,5,3 ′-triiodothyronine versus thyroxine in rats, as assessed from 3,5,3′-triiodothyronine levels in fetal tissues
Authors: de Escobar Gabriella Morreale , Obregón María Jesís , de Oña Carmen Ruiz , del Rey Francisco Escobar
Published: December 2008

Abstract. Thyroxine (T4) is transferred from the mother to the hypothyroid rat fetus late in gestation, mitigating T4 and T3 deficiency in fetal tissues, the brain included. We have now compared the effects of maternal infusion with T3. Normal and thyroidectomized rats were started on methimazole (MMI) on the 14th day of gestation, given alone, or together with a constant infusion of 0.45 μg (0.69 nmol) T3 or of 1.8 μg (2.3 nmol) T4/100 g per day. Maternal and fetal samples were obtained at the 21st day of gestation. The doses of T3 and T4 were biologically equivalent for the dams, as assessed from maternal plasma and tissue T3, and plasma TSH levels. MMI blocked the fetal thyroid; T4 and T3 levels were low in all fetal tissues, and fetal plasma TSH was high. Maternal infusion with T4 mitigated both T4 and T3 deficiency in all fetal tissues, the brain included, and decreased fetal plasma TSH. In contrast, infusion of T3 normalized fetal plasma T3 and increased the T3 levels in several tissues, but not in the brain. Neither did it decrease the high fetal plasma TSH levels. The results show that when the fetus is hypothyroid, T3 crosses the rat placenta at the end of gestation, but does not affect all tissues to the same degree. In contrast to the effects of maternal T4, maternal T3 does not alleviate the T3 deficiency of the brain or, presumably, of the thyrotrope. Thus, end-points of thyroid hormone action related to TSH release should not be used to measure transfer of maternal T3 to the fetal compartment. Moreover, T4 should be given, and not T3, to protect the hypothyroid fetal brain.
Chronic administration of a gonadotropin-releasing hormone (GnRH) agonist affects testicular microvasculature
Authors: Mayerhofer A. , Dubé D.
Published: December 2008

Abstract. Three months of daily sc injections of adult male dogs with the gonadotropin-releasing hormone agonist (GnRH-A) [D-Trp6, des-Gly-NH210]GnRH ethylamide produced significant decrease in the diameter of seminiferous tubules and conspicuously altered the ultrastructure of testicular microvasculature. In contrast to capillaries and venules in untreated controls, which had typical continuous endothelial layers surrounded by a basal lamina, in testes of dogs chronically treated with GnRH-A, 14.3% of the capillaries and 21.2% of the venules showed wide (30–500 nm) endothelial gaps. In a few capillaries (1.7%) and venules (4%) endothelial fenestrations were found. A high percentage of capillaries (59.3%) and venules (32.8%), with endothelial gaps or continuous endothelium were surrounded by multiple layers of basal lamina. All arterioles, 24.7% of the capillaries and 42.6% of the venules showed the normal features as found in the controls. Superfluous basal laminae, not associated with cells were present in the testes of the chronically treated dogs, but were also found after 4 months of recovery from the GnRH-A treatment. However, within 4 months after cessation of the GnRH-A treatment, the diameters of the seminiferous tubules were comparable to those in untreated controls. Capillaries and venules with endothelial gaps or fenestrations were completely absent. All arterioles, 43.6% of the capillaries and 65.6% of the venules revealed the normal features of continuous endothelium. However, 56.4% of the capillaries and 34.4% of the venules were characterized by superfluous layers of basal lamina. Thus, impaired spermatogenesis, as reflected by significantly decreased tubular diameters, owing to chronic administration of this GnRH-A in the dog is accompanied by major alterations of the testicular microvasculature. Although the mechanism(s) of these vascular changes are unclear, we propose that testicular microvessels could be a factor involved in the inhibition of spermatogenesis by chronic GnRH-A treatment.
Thyroid function in hyperemesis gravidarum
Authors: Swaminathan R. , Chin R. K. , Lao T. T. H. , Mak Y. T. , Panesar N. S. , Cockram C. S.
Published: December 2008

Abstract. Plasma total T4 (TT4), T3 (TT3), free T4 (FT4), free T3 (FT3), thyroxine binding globulin, hCG, and erythrocyte zinc content were measured in 43 women with uncomplicated pregnancy and in 71 patients admitted with hyperemesis gravidarum. Plasma concentration of thyroid hormones in hyperemesis subjects showed wide variability and 32% of subjects had high TT4 (higher than mean +2 sd of normal pregnant subjects), 33% had high FT4, 20% had high TT3, and 20% had high FT3. Red cell zinc content, a tissue marker of thyroid status, in the hyperthyroxinemic subjects was not different from that of normothyroxinemic hyperemesis subjects or of subjects with uncomplicated pregnancy. The elevated TT4 concentration decreased spontaneously in all but two of the hyperemesis subjects to normal pregnant levels. The plasma FT4 concentration at presentation correlated with plasma hCG in hyperemesis gravidarum (partial correlation coefficient r = 0.411, P< 0.01), but not in normal pregnancy (partial correlation coefficient r = 0.043) after allowing for the effect of gestational age. We conclude that approximately one third of hyperemesis subjects show transient hyperthyroxinemia and suggest that hCG or a molecular variant of hCG may stimulate the thyroid gland.
Enzyme-immunoassay for estrogen receptors in human pituitary adenomas
Authors: Nakao Haruyoshi , Koga Masafumi , Arao Masayo , Nakao Makoto , Sato Bunzo , Kishimoto Susumi , Saitoh Yoichi , Arita Norio , Mori Shintaro
Published: December 2008

Abstract. We have performed an enzyme-immunoassay for estrogen receptor on 56 human pituitary adenomas and compared the results with a single point estradiol binding assay. There was a significant positive correlation between the two assays of cytoplasmic estrogen receptor (r = 0.960). Normal human pituitaries (N = 2) had an estrogen receptor concentration of 17 fmol/mg protein by enzyme-immunoassay. Of 14 prolactinomas, 6 (43%) contained estrogen receptor with a concentration of 33.5 ± 7.4 (mean ± sem) fmol/mg protein. Six of 11 (55%) macroprolactinomas were estrogen receptorpositive, whereas all 3 microprolactinomas were estrogen receptor-negative. Only one (13%) of 8 GH- and PRL-secreting adenomas, and 3 of 6 (50%) gonadotropin-secreting adenomas were estrogen receptor-positive; the latter had a concentration of 13.5 ± 1.6 fmol/mg protein. Estrogen receptor was not detected in 21 pure GH-secreting adenomas and 7 nonsecreting adenomas. These results demonstrate the precise frequency of estrogen receptor in various human pituitary adenomas, since enzyme-immunoassay as well as single point estradiol binding assay could detect estrogen receptor even in small specimens. Enzyme-immunoassay is suitable for evaluation of estrogen receptor status in human pituitary adenomas.
Assessing adrenocortical activity by determining levels of urinary free cortisol and urinary 6β-hydroxycortisol
Authors: Nakamura Jiro , Yakata Minoru
Published: December 2008

Abstract. A comparative study of urinary free cortisol and urinary 6β-hydroxycortisol levels as a diagnostic test for hypercortisolemic states was carried out by measuring the excretion in 24-h specimens from 289 apparently healthy subjects and 10 Cushing patients. The diurnal variations of both variables were examined in normal subjects and subjects with altered adrenal activities. Two of the 289 apparently normal subjects had high values of urinary free cortisol; one had a high, the other a normal 6β-hydroxycortisol level; they were later diagnosed as having Cushing's syndrome and infertility, respectively. Three other subjects had high values of the urinary variables, but during 5 years of follow-up did not show any clinical evidence of hypercortisolism. The two urinary variables gave no false-negative results in the Cushing patients. The diurnal variation revealed that levels of 6β-hydroxycortisol change in parallel with those of free cortisol in normal subjects and in subjects with altered adrenal activities. However, the ratio of 6β-hydroxycortisol to free cortisol during the diurnal variation varied from low values when free cortisol levels were high to high values when free cortisol levels were low. In normal subjects, 1 mg of dexamethasone taken orally at 23.00 h completely suppressed the levels of both variables on the following day. It is concluded that urinary 6β-hydroxycortisol is correlated to urinary free cortisol so that measurement of urinary 6β-hydroxycortisol levels can be used as a diagnostic test for hypercortisolism in a way comparable to the method using urinary free cortisol.
A deficient response of atrial natriuretic peptide to volume overload in Gordon's syndrome
Authors: Välimäki M. , Pelkonen R. , Tikkanen I. , Fyhrqvist F.
Published: December 2008

Abstract. Gordon's syndrome was diagnosed in a 19-year-old woman who had hypertension, hyperkalemia and hyperchloremic acidosis. In family screening, hyperkalemia and hyperchloremic acidosis were also found in the patient's mother and brother. The proband and her brother were studied and showed normal glomerular function with normal renal sodium conservation and urine acidification mechanisms. The levels of plasma aldosterone were normal in both subjects. The renin activity was low in the proband but normal in the brother. Both the basal and the volume-stimulated plasma concentration of atrial natriuretic peptide was low in the two patients. As compared with controls, the kaliuretic response to infusion of sodium chloride was not decreased in the patients. Hydrochlorothiazide promptly corrected the acidosis and the hyperkalemia as well as normalized the raised blood pressure of the proband. We suggest that a deficiency of atrial natriuretic peptide rather than an unusual avidity for sodium chloride reabsorption by the renal tubules plays a significant pathogenetic role in Gordon's syndrome.
Central effect of the enkephalin analogue FK-33824 on vasopressin secretion in conscious sheep
Authors: Wang Xiaoming , Tresham Janette J. , Congiu Mario , Scoggins Bruce A. , Coghlan John P.
Published: December 2008

Abstract. The role of opioids in the regulation of arginine vasopressin release from the posterior pituitary is a subject of controversy. In the present study, we examined the effects of central administration of met-enkephalin, leu-enkephalin, the enkephalin analogue FK-33824, and the opiate antagonist naloxone, and the effects of systemic administration of met-enkephalin and FK-33824 on AVP secretion in conscious normal sheep. Intracerebroventricular infusion of FK-33824 significantly increased the plasma concentration of immunore-active AVP in a dose-dependent manner, but met-enkephalin, leu-enkephalin and naloxone failed to change plasma concentration of AVP. Intravenous infusion of met-enkephalin and FK-33824 also failed to change plasma concentration of AVP. The opiate antagonist naloxone given both centrally and systemically attenuated the increase in plasma concentration of AVP induced by FK-33824. We conclude that basal AVP release is stimulated by central administration of FK-33824.
Calcitonin inhibition of growth hormone-releasing hormone-induced GH secretion in normal men
Authors: Ceda Gian Paolo , Denti Licia , Ceresini Graziano , Rastelli Gianni , Dotti Claudio , Cavalieri Simona , Valenti Giorgio , Hoffman Andrew R.
Published: December 2008

Abstract. Calcitonin has been shown to modulate pituitary hormone secretion in a variety of ways. In this study we examined the effects of a salmon calcitonin infusion on GHRH-induced GH secretion in 5 normal men. In addition, in vitro experiments were performed using primary cultures of rat anterior pituitary cells in order to examine whether there is a direct pituitary effect of CT. Infusion of CT significantly blunted the GH response to GHRH in all subjects without affecting basal GH secretion or plasma calcium levels. Infusion of CT was accompanied by significant increases in ACTH, β-endorphin, cortisol and free fatty acid levels, and by a significant decrease in serum insulin levels. The addition of CT to primary cultures of rat pituitary cells did not alter basal or stimulated secretion of GH or ACTH. These results indicate that: 1) CT blunts the GH response to GHRH; 2) CT infusion results in the stimulation of the hypothalamicpituitary-adrenal axis, and 3) this effect is probably exerted at the hypothalamic level, since no direct activity of CT was documented in vitro on either GH or ACTH secretion.
Influence of estrogen administration on growth hormone response to GHRH and L-Dopa in patients with Turner's syndrome
Authors: Schober E. , Frisch H , Waldhauser F. , Bieglmayr Ch.
Published: December 2008

Abstract. The modulating effect of estrogen on GH secretion was studied in 22 patients with Turner's syndrome. Estrogen administration (0.5 μg/kg ethinylestradiol) for a period of 4 weeks resulted in a significant increase in basal GH concentrations (2.6 vs 4.8 μg/l, P< 0.01). The L-Dopa-stimulated GH concentrations were also significantly increased (P< 0.01), whereas no effect of estrogen substitution on GH responses to GHRH (1–44) and Sm-C levels was seen. Our findings demonstrate a priming effect of estrogen on GH secretion in patients with Turner's syndrome. These patients generally lack the puberty-associated rise in GH secretion, which might be due to ovarian failure and the concomitant estrogen deficiency.
Graves' hyperthyroidism following primary hypothyroidism: sequential changes in various activities of thyrotropin receptor antibodies
Authors: Cho B. Y. , Shong Y. K. , Lee H. K. , Koh C.-S. , Min H. K.
Published: December 2008

Abstract. A 40-year-old male who developed Graves' hyperthyroidism following primary hypothyroidism is reported. He presented with clinical signs of hypothyroidism and concomitant myasthenia gravis. The thyroid was not palpable. He was treated with T4, pyridostigmine and prednisolone. One year later he developed hyperthyroidism and goitre. His initial serum IgG had no intrinsic thyroid stimulating activity, but showed almost complete inhibition of TSH-stimulated cAMP generation (99.4%, normal <38%) and [3H]thymidine incorporation (99.5%, normal<40%) into rat thyroid cells, FRTL-5 cells, with very high activity (80.2%, normal <15%) of TSH binding inhibitor immunoglobulin. When he developed hyperthyroidism and goitre, his IgG showed a strong thyroid stimulation, both cAMP production (27-fold increase) and [3H]thymidine incorporation (5.5-fold increase). No inhibitory activities were noted. These findings suggest that clinical states of autoimmune thyroid diseases can be changed in accordance with changes of functional properties of TSH receptor antibodies.
Immunocytochemical localization of the nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen
Authors: Luo M. , Faure R. , Tong Y. A. , Dussault J. H.
Published: December 2008

Abstract. A monoclonal antibody was used for the localization of the nuclear T3 receptor in different tissues of the adult rat: the liver, kidney, heart, lung, spleen, testis, and pituitary. In the liver, the immunoreactivity was found uniformly distributed in the nuclei of hepatocytes. Sections incubated with a control ascitic fluid or with the same ascitic fluid pre-adsorbed with purified receptor showed no specific staining. In the kidney, the immunoreactivity was higher in the epithelial cell of the proximal convoluted tubes and juxtaglomerular cells. In the heart, only the myocardial cells were stained. In the lung, the immunoreactivity was confined to type II pneumocytes and alveolar macrophages. In the spleen, only a few mature lymphocyte and macrophage cell nuclei were stained. These results show that: 1) the abundance of the nuclear T3 correlates with previous studies using hormone binding techniques; 2) the nuclear T3 receptor is selectively located in certain cell types, which possess a precise local function.
Effects of urea on the in vitro production of prostaglandins and on urinary excretion in Brattleboro rats
Authors: Bojesen Eigil , Bojesen Inge N.
Published: December 2008

Abstract. Brattleboro rats with hereditary diabetes insipidus make it possible to investigate effects of the urea concentration on the in vitro and in vivo production of prostaglandins E2 and F2α (PGE2 and PGF2α) by the renal papilla independently of any vasopressin effects. The rates of prostaglandin production in vitro are increasing between 100 and 1030 mmol/l urea and decreasing above 1030 mmol/l. The ratio PGE2/PGF2α remains constant at about 4. Normally hydrated and 24 h water-deprived animals in steady state of urine formation were compared in vivo. Urine osmolality increased from 167 ± 6 (N = 5) to 1113 ± 35 (N = 15) mosmol/kg water and papillary urea concentration from 50 ± 7 to 304 ± 19 mmol/l after water deprivation. Urinary excretion rates of PGF2α increased from 0.83 ± 0.12 to 3.80 ± 0.37 ng/h. The excretion of PGE2 was unaffected. PGE2 + PGF2α excretion rates increased from 1.62 ± 0.25 to 4.61 ± 0.42 ng/h. These values are in accordance with values predicted from work with Sprague-Dawley rats. Together with previously published data on Sprague-Dawley rats these results indicate that variations of prostaglandin production in the conscious rat in steady state of urine formation can be accounted for by variations of plasma vasopressin and of papillary urea concentration. Variations in the excretion fraction are due to other causes.
Cholecystokinin, gastrin and their precursors in pheochromocytomas
Authors: Bardram Linda , Hilsted Linda , Rehfeld Jens F.
Published: December 2008

Abstract. Using sequence-specific radioimmunoassays before and after cleavage with trypsin and carboxypeptidase B, we have examined the occurrence and molecular nature of cholecystokinin (CCK) and gastrin peptides in bioactive (i.e. α-carboxyamidated) as well as non-amidated precursor forms in extracts from 13 human pheochromocytomas. All but one tumour contained amidated CCK, but only in moderate amounts (≤ 20 pmol/g tissue). In contrast to the complete sulphation in tissues which normally produce CCK (the brain and small intestine), the amidated adrenal CCK peptides were poorly sulphated (≤ 17%). Four pheochromocytomas, including the one without amidated CCK, contained between 28 and 0.2 pmol amidated gastrin/g, mainly in the form of sulphated gastrin-17. In addition, all tumours contained biosynthetic precursors of both CCK and gastrin. In most extracts there was more precursor than bioactive peptide(s), the progastrin concentration ranging up to 338 pmol/g. The results show that pheochromocytomas synthesize CCK and gastrin. The posttranslational processing differs, however, markedly from that of the principal CCK and gastrin producing tissues, with respect to both proteolytic cleavages and amino acid derivatization. This emphasizes that accurate quantitation in tumours requires assays which measure the translation products irrespective of their degree of processing.
Generalized deficiency of 3,5,3'-triiodo-L-thyronine (T3) in tissues from rats on a low iodine intake, despite normal circulating T3 levels
Authors: del Rey Francisco Escobar , de Oña Carmen Ruiz , Bernal Juan , Obregón Maria Jesus , de Escobar Gabriella Morreale
Published: December 2008

Abstract. Rats fed a low iodine diet have decreased total and nuclear T3 concentrations in the liver and brain, as compared with rats supplemented with iodine, possibly because of the very low plasma and tissue T4 pools in low-iodine diet rats, leading to decreased intracellular generation of T3 in those tissues. If so, T3 levels should not decrease in heart and skeletal muscle, as plasma T3 is normal in low-iodine diet rats and these two tissues derive their intracellular T3 directly from plasma T3. We have studied this point in male rats fed a low-iodine diet, a low-iodine diet + iodine, and the stock diet. As in previous studies, low-iodine rats had very low plasma T4 and high plasma TSH levels, plasma T3 levels being normal. Liver T3 decreased, and so did the brain T3 levels despite a compensatory increase in type II 5' iodothyronine deiodinase activity. Contrary to expectations, T3 concentrations were lower in the heart and skeletal muscle of low-iodine diet rats. Attempts to clarify the possible mechanism(s) involved have been unsuccessful so far. The present results show that, despite normal plasma T3, a deficiency of T3 occurs in more tissues of rats on a low iodine intake than previously assumed. If the present results are pertinent to inhabitants from areas with severe iodine dificiency, it would appear that they might suffer from a generalized tissue T3 deficiency (and hypothyroidism?), even if overt clinical signs are not usually present.
Atrial natriuretic peptide in pregnant and lactating goats
Authors: Olsson K. , Karlberg B. E. , Eriksson L.
Published: December 2008

Abstract. Plasma concentrations of atrial natriuretic peptide (ANP) were measured in 6 goats during pregnancy, lactation and a nonpregnant, nonlactating (= control) period before and during a rapid iv load of 0.9% NaCl. The volume of the load was 20% of blood volume. The infusions increased central venous pressure by 7 ± 1 mmHg during pregnancy and 8 ± 1 mmHg during lactation. Before infusions plasma ANP concentrations were 5.7 ± 0.7 pmol/l (control period), 10.8 ± 1.8 pmol/l (pregnancy;P< 0.05),and6.5 ± 1.5 pmol/l (lactation;NS).ANP increased significantly in all periods. Maximal values were 12.5 ± 1.5 (control period), 25.5 ± 2.3 (pregnancy; P< 0.01 vs control period, P<0.05 vs lactation), and 13.0 ± 1.6 (lactation; NS). Renal Na excretion increased similarly during pregnancy and control period, but slightly more during lactation. In 4 of the goats iv infusions of ANP (1 μg/min, 60 min) were given. The infusions caused natriuresis during the control period, but not during pregnancy and lactation, despite more than 10-fold increases of plasma ANP levels. In conclusion, our results indicate that although plasma ANP concentration rose to high levels during acute NaCl loading in pregnant goats, this effect was not important for the natriuresis. Instead, the natriuretic response to ANP appears attenuated during pregnancy, and also during lactation.
Enhanced circadian rhythm of melatonin in anorexia nervosa
Authors: Tortosa Federico , Puig-Domingo Manuel , Peinado Miguel-Angel , Oriola Josep , Webb Susan M. , de Leiva Alberto
Published: December 2008

Abstract. Plasma melatonin circadian profiles were investigated in a group of 4 patients with anorexia nervosa and 4 healthy regularly cycling women. There were no differences in the mean age of both groups, whereas the anorexia nervosa patients had lower mean body weight (37.8 ± 2.0 vs 57.0 ± 4.9 kg) and body mass index (13.9 ± 1.1 vs 20.8 ± 2.0). Samples were collected every 2 h and plasma melatonin was measured by using a RIA with an iodinated tracer. Anorexia nervosa patients exhibited higher diurnal (60.7 ± 1.8 vs 25.4 ± 1.72 pmol/l, P< 0.02) and nocturnal (419.2 ± 37.4 vs 108.0 ± 33.6 pmol/l), P< 0.001) mean plasma melatonin concentrations. There were no differences in the time peak for nocturnal melatonin secretion in both groups, detected at 02.00 h. In anorexia nervosa, the melatonin circadian profile paralleled that observed in the control group, indicating that the increased melatonin values for anorexia nervosa were probably due to an enhanced secretory pineal function rather than an impaired melatonin metabolism. These results suggest a participation of the pineal gland in the pathophysiology of anorexia nervosa.
Renal and blood pressure changes in response to vasopressin antagonism in the New Zealand genetically hypertensive rat
Authors: Ashton N. , Balment R. J.
Published: December 2008

Abstract. The effects of a mixed pressor and antidiuretic vasopressin antagonist on blood pressure and renal function have been investigated in New Zealand genetically hypertensive and normotensive rats. Vasopressin antagonism was associated with a diuresis, compensatory polydipsia and kaliuresis in both normotensive and hypertensive animals. Hypertensive animals alone exhibited a natriuresis and a fall in systolic blood pressure, which was associated with a reduction in water balance and plasma sodium compared with antagonisttreated normotensive animals. The data suggest that vasopressin may exert a long-term influence on blood pressure through renally rather than vascularly mediated effects.
Thyroid hormone stimulated glucose uptake in human mononuclear blood cells from normal persons and from patients with non-insulin-dependent diabetes mellitus
Authors: Kvetny J. , Matzen L.
Published: December 2008

Abstract. Thyroxine and T3 induced oxygen comsumption and glucose uptake were studied in vitro in mononuclear blood cells isolated from patients with non-insulindependent diabetes mellitus (NIDDM) and from nondiabetic control persons. Cellular oxygen comsumption and glucose uptake were promptly increased by physiological and supraphysiological concentrations of T3 and T4 in a dose-dependent manner (50–5000 nmol/l), whereas rT3 and T2 had no stimulatory effect. The effect of T3 and T4 was independent of new protein synthesis in that it was not blocked by tunicamycin (1 mg/l) and tiothepa (75 mg/l). Examination of stimulation of cells from control subjects and patients with NIDDM revealed an identical oxygen comsumption, whereas the thyroid hormone-induced glucose uptake was significantly increased in cells from patients with NIDDM. T4 (5 μmol/l) stimulation in controls: 1.34 ± 0.23 mmol · l−1 (mg DNA)−1· h−1, in NIDDM: 3.24 ± 0.77 mmol · l−1 · (mg DNA)−1 · h−1, P< 0.05 (mean ± so). These studies indicate that T4 as well as T3 increases cellular oxygen consumption and glucose uptake and that this stimulation is independent of new protein synthesis. Examination of cells from patients with NIDDM revealed an increased thyroid hormone induced glucose uptake, indicating increased thyroid hormone sensitivity. This observation contrasts the well known insulin insensitivity, suggesting separate mechanisms for glucose uptake elicited by insulin and thyroid hormones.
The effect of long-term pulsatile GnRH administration on the 24-hour integrated concentration of GH in hypogonadotropic hypogonadic patients
Authors: Giusti M. , Torre R. , Cavagnaro P. , Attanasio R. , Traverso L. , Giordano G.
Published: December 2008

Abstract. Measurement of integrated concentration of GH by means of continuous withdrawal sampling is a method of evaluating physiological hormonal secretion. Integrated concentration of GH was evaluated in 5 subjects with idiopathic hypogonadal hypogonadism (range 19–27 years) and in a 17-year-old male with idiopathic delay of puberty (5 males, 1 female) before and 30–240 days after the start of pulsatile GnRH administration. Gonadotropins and testosterone or 17β-estradiol were restored, whereas 24-h integrated concentration of GH (before therapy 5.4 ± 1.3 IU/l; during GnRH 8.1 ± 2.0 IU/l; P< 0.05) was increased by GnRH therapy. However, no correlation was found between GH levels and sex steroid concentrations during GnRH pulsatile administration. These data further confirm that a physiological increase in gonadotropins and sex steroids can modulate GH synthesis and/or release.
The effect of the long-acting somatostatin analogue SMS 201–995 on ACTH secretion in Nelson's syndrome and Cushing's disease
Authors: Lamberts Steven W.J. , Uitterlinden Piet , Klijn Jan M. G.
Published: December 2008

Abstract. Chronic therapy of a patient with Nelson's syndrome for 2 years with 300 μg SMS 201–995 per day resulted in a significant decrease in circulating ACTH levels, normalization of the visual field defect and of loss of visual acuity of one eye, and stabilization of tumour growth, without radiological evidence of shrinkage of the pituitary tumour. In two other patients with Nelson's syndrome, SMS 201–995 acutely inhibited circulating ACTH levels. This effect could be shown best if cortisol replacement was temporarily withheld. SMS 201–995 did not affect plasma ACTH and cortisol levels in three patients with untreated Cushing's disease.