bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferential release of proinsulin relative to insulin in non-insulin-dependent diabetes mellitus
Authors: Deacon C. F. , Schleser-Mohr S. , Ballmann M. , Willms B. , Conlon J. M. , Creutzfeldt W.
Published: December 2008

Abstract. A radioimmunoassay, using an antiserum that is specific for human proinsulin, has been used to study the response of serum proinsulin to low (25 g) and high (75 g) oral glucose loads in non-obese patients with noninsulin-dependent diabetes mellitus (NIDDM). Diabetic patients were treated by diet only (N = 8) or were receiving oral anti-hyperglycemic agents (N = 8) and therapy was not interrupted during the study. In the fasted state, proinsulin concentrations were higher (P<0.05) in the drug-treated patients (31 ± 3 pmol/l (sem)) compared with age- and weight-matched healthy subjects (22 ± 2 pmol/l; N = 10), but concentrations in the diet-treated patients 25 ± 3 pmol/l) were not significantly different. Following 25 g and 75 g glucose loads, the rises in serum immunoreactive insulin and C-peptide concentrations in both groups of diabetic patients were impaired and delayed relative to those in the control subjects. The responses of serum proinsulin, however, were not significantly different in the NIDDM patients compared with controls at any time point up to 180 min except in the case of drugtreated patients receiving 25 g of glucose who had elevated (P< 0.05) proinsulin concentrations at 150 min and 180 min after ingestion. It is concluded that NIDDM is not associated with an exaggerated release of proinsulin in response to glucose compared with healthy subjects, but the islets have maintained the ability to release proinsulin better than the ability to release insulin.
Pulsatile gonadotropin secretion in pubertal children with chronic renal failure
Authors: Schaefer F. , Stanhope R. , Scheil H. , Schönberg D. , Preece M. A. , Schärer K.
Published: December 2008

Abstract. We have examined physiological nocturnal secretion of gonadotropins in 6 boys and 2 girls with end-stage renal disease, who had either delayed or disturbed puberty. The 5 patients treated by dialysis had reduced gonadotropin pulsatility for their stage of pubertal maturation, whereas the 3 patients with successful kidney grafts demonstrated a higher nocturnal rise and increased amplitude of gonadotropin pulsatility. It is suggested that the improved gonadotropin pulsatility of transplanted patients is due to their restored renal function.
Growth hormone (GH) responsiveness to GHRH in normal adults is not affected by short-term gonadal blockade
Authors: Lima L. , Arce V. , Lois N. , Fraga C. , Lechuga M.J. , Tresguerres J. A. F. , Devesa J.
Published: December 2008

Abstract. The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1 μg/kg) in normal adults volunteers (aged 18–24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 μg/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E2), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E2 receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH-deficiency during the peripubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E2 receptor blockade. Since the hypothalamic-somatotrope rhythm was altered by both these farmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E2
Allogenic bone marrow transplantation in adults: endocrine sequelae after 1–6 years
Authors: Benker G. , Schäfer U. , Hermanns U. , Mahmoud M. K. , Olbricht Th. , Schulte H. M. , Windeck R. , Reinwein D.
Published: December 2008

Abstract. Twenty-three patients (13 females, 10 males) with panmyelopathy (N = 9), chronic leukemia (N = 5), and acute leukemias (N = 9) were studied 1 to 6 years following allogenic bone marrow transplantation. All patients had received conditioning treatment with cyclophosphamide prior to aBMT, and 2 of the patients with bone marrow aplasia and all of the leukemia patients had been given radiotherapy. An endocrine assessment was performed by means of TRH, GnRH, oCRF and GHRH tests and estimation of thyroid and gonadal hormones. Whereas pituitary-adrenal function appeared to remain stable, there was a 17.4% incidence of subclinical hypothyroidism (25% of the irradiated patients). Growth hormone reserve was diminished, and ovarian failure occurred in all female patients after radiotherapy, whereas in the men, only a moderate elevation of gonadotropins was observed. Our results warrant observation of thyroid and gonadal function, and in children of growth hormone secretion, after allogenic bone marrow transplantation. They also show that replacement therapy may be needed in some patients.
Hormonal control of plasminogen activator secretion in organ culture of rat ventral prostate
Authors: Martikainen Paula , Suominen Jyrki , Vihko Kimmo
Published: December 2008

Abstract. The usefulness of plasminogen activators (PAs) in the follow-up of the secretory function of the prostate in culture, as well as the hormonal control of these secretory proteins was studied. Organ culture of rat ventral prostate was used as an experimental model. PA secreted into the culture medium during the two weeks' culture period was of the urokinase-type in all culture conditions, as determined by zymography. The highest activities at the end of culture were found in the involuting prostate in cultures without any hormones. As the epithelial component is strongly reduced in the involuted explants, these high activities were suggested to be derived from stroma. Corticosterone (10−7 mol/l) and insulin (80 U/l) reduced significantly the secretion of PA, and this reduction was attenuated when the favourable effect of these hormones on the maintenance of morphology and tissue weight was taken into account. Testosterone (10−7 mol/l) increased significantly the secretion of PA in all hormone-treated cultures, which could be due to the increased secretory activity of the epithelium. Interactions between the hormones were significant, i.e. the effects of the hormone combinations were different and could not be calculated from the separate effects of these hormones. Even though the general growth and function of the prostate is strictly androgen-controlled, these results suggest that the control of PA secretion is multihormonal.
A correlative study between glucocorticoid receptor levels in human mononuclear leukocytes and biochemical data in Cushing's disease
Authors: Pardes E. M. , de Yampey J. W. , Soto R.J. , Moses D. F. , De Nicola A. F.
Published: December 2008

Abstract. We determined glucocorticoid receptors in human monouclear leukocytes in 9 patients with Cushing's disease, in order to correlate them with laboratory data. Receptors were measured by a whole-cell assay method, after incubation with [3H]-dexamethasone in the presence or absence of excess unlabelled hormone. In Cushing's disease, there were 4425 ± 364 sites/cell (N = 9), similar to in the controls: 4473 ± 476 (N = 10); average Kd was 2.42 ± 0.52 nmol/l (N = 3) similar to in the controls: 2.0 ± 0.20 nmol/l (N = 3). In Cushing's patients we found significant negative correlations between basal glucocorticoid receptors and: 1) morning blood cortisol (r = −0.67, P< 0.05), and 2) 17-ketogenic steroids after 2 mg of dexamethasone (r = −0.85, P< 0.01). No correlations were observed with afternoon blood cortisol, free urinary cortisol, basal and post-8-mg dexamethasone 17-ketogenic steroids, TRH-TSH area, urinary calcium. plasma glucose, or systolic blood pressure. Conclusions: In Cushing's disease, a subtle receptor down-regulation may exist, as suggested by the inverse relationship between glucocorticoid receptors and morning blood cortisol. Secondly, the relationship between basal receptors and 17-ketogenic steroids after 2 mg of dexamethasone suggests that glucocorticoid receptors in human mononuclear leukocytes could reflect the sensitivity of the nervous system-pituitary-adrenal axis to dexamethasone inhibition.
Properties of 5′-deiodinase of 3,3′,5′-triiodothyronine in rat skeletal muscle
Authors: Tsukahara Fujiko , Nomoto Teruko , Maeda Michiko
Published: December 2008

Abstract. To characterize rT3 5′-deiodinase (5′D) in rat skeletal muscle, the effects of altered thyroid status and PTU on rT3 5′D were studied. rT3 5′D activity was measured by incubating homogenates of rat skeletal muscle with [125]rT3, iodine labelled in the outer ring, in the presence of 20 mmol/l DL-dithiothreitol. This activity was observed to increase significantly 24 h after a single sc injection of T3 (75 μg/kg). The increase following the daily administration of this drug (15 or 75 μg/kg) for 3 and 14 days was dependent on the dose and number of previous days of injection. A significant decrease in activity was observed 2 weeks after thyroidectomy. The addition of 0.1 mmol/l 6-n-propyl-2-thiouracil (PTU) to the incubation medium in vitro caused a marked reduction in the activity in homogenates of skeletal muscle from hypothyroid, euthyroid and hyperthyroid rats. PTU, present at 0.05% in the drinking water for 2 weeks virtually abolished it. The properties of rT3 5′D in rat skeletal muscle thus appear to be essentially the same as those of type I enzyme with respect to response toward altered thyroid status and PTU.
Hyperprealbuminemia, euthyroid hyperthyroxinemia, Zollinger-Ellison-like syndrome and hypercorticism in a pancreatic endocrine tumour
Authors: Maye Ph. , Bisetti A. , Burger A. , Docter R. , Gaillard R. , Griessen M. , Pelte M. F.
Published: December 2008

Abstract. Prealbumin, one of the main thyroxine transport proteins, has recently been shown to be a valuable immunohistochemical marker of neuroendocrine tumours. We report the case of a multisecretory pancreatic endocrine tumour whose prealbumin secretion was so high that it produced a peak on routine serum protein electrophoresis and induced a euthyroid hyperthyroxinemia. The maximal binding capacity of prealbumin for thyroxine was indeed markedly increased, whereas its affinity for this hormone was normal. The tumour was associated with gastric hyperacidity and hypergastrinemia thereby evoking a Zollinger-Ellison syndrome. The secretin stimulation test and gastrin tumoural immunohistochemistry were, however, negative. We suggest that the concomitant tumoural production of gastrin-releasing peptide was responsible for the gastric hyperacidity and hypergastrinemia. This hormone probably also accounted for a moderate hypercorticism.
Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: comparison with activities of thyrotropin-binding inhibitor immunoglobulins
Authors: Cho B. Y. , Shong Y. K. , Lee H. K. , Koh C.-S. , Min H. K.
Published: December 2008

Abstract. We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H] thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3,0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H] thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P<0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P<0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1–100%) and thyroid growth inhibiting immunoglobulin (57.4–100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.
Effect of atrial natriuretic peptide on catecholamine release from human pheochromocytoma
Authors: Nakamaru Mitsuaki , Ogihara Toshio , Saito Hiroshi , Rakugi Hiromi , Hashizume Kiyoko , Yamatodani Atsushi , Wada Hiroshi , Kumahara Yuichi
Published: December 2008

Abstract. The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 μg ·kg−1·min−1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 ± 0.10 to 1.19 ± 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 ± 0.01 to 0.05 ± 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10−8 to 10−5 mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10−7 mol/l) did not affect the increase in catecholamine release induced by glucagon (10−5 mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.
Plasma growth hormone profile in acromegaly before and ten days after transsphenoidal surgery
Authors: Edén Staffan , Bengtsson Bengt-Åke , Albertsson-Wikland Kerstin , Elfversson Jörgen , Lindstedt Göran , Lundberg Per-Arne , Petruson Björn , Rosberg Sten
Published: December 2008

Abstract. Profiles of plasma GH, plasma somatomedin-C and serum PRL concentrations as well as serum GH response to iv TRH were determined in 11 patients with acromegaly before and 10 days after surgery. Blood for profile determinations was drawn from a peripheral vein with a continuous withdrawal pump changing the recipient tube at 30-min intervals. Before surgery all patients had high plasma GH concentrations with irregular peaks and somatomedin-C concentrations were elevated. The response to TRH was abnormal in 8 patients. Three patients had slightly elevated PRL concentrations and one had high PRL concentration (6900 mU/l). Ten days after surgery GH concentrations were still high in 2 patients (>5 mU/l), as were somatomedin-C concentrations (3.2 and 2.4 U/l, respectively). In 3 patients basal GH concentrations were <5 mU/l and somatomedin-C concentrations were normal, but there were no major peaks in plasma GH concentrations. In 2 patients major peaks in GH concentrations appeared after surgery, but basal GH concentrations were 1.9 and 0.95 mU/l, respectively. One patient with hyperprolactinemia still had slightly elevated PRL concentration (486 mU/l), but the response to TRH was normalized. Finally, in 4 patients, mean GH concentrations were markedly reduced, somatomedin-C concentrations normalized and apparently normal plasma GH profiles appeared with low or undetectable basal levels separating major peaks. The results indicate that in some patients with acromegaly apparently normal GH secretion can be demonstrated 10 days postoperatively. Characterization of circadian GH rhythms during the early postoperative stage may contribute to the evaluation of the effect of surgery.
Simultaneous inhibition by pirenzepine of the GH responses to GnRH and TRH in insulin-dependent diabetics and in patients with major depression
Authors: Coiro V. , Volpi R. , Capretti L. , Speroni G. , Castelli A. , Mosti A. , Marchesi C. , Gardini E. , Rossi G. , Chiodera P.
Published: December 2008

Abstract. The present study was undertaken in order to establish whether muscarinic cholinergic receptors are involved in the anomalous GH response to GnRH in men with insulin-dependent diabetes mellitus and in male patients with major depression. For this purpose, 16 male diabetics, 18 depressed men and 9 normal controls were tested with GnRH (25 μg iv) with and without previous treatment with the muscarinic cholinergic receptor blocker pirenzepine (40 mg iv 10 min before GnRH). Additional experiments with TRH (200 μg iv 10 min after pirenzepine) were performed in the same subjects and used for comparison between responders to TRH and GnRH. The administration of GnRH stimulated GH release in 12 out of the 16 diabetics and in 8 out of the 18 depressed patients, but not in the normal controls. Control and diabetic non-responders to GnRH did not respond to TRH. In contrast, all diabetic responders to GnRH, except 2, showed paradoxical GH responses to TRH. All depressed responders to GnRH and 3 of the non-responders, were responsive to TRH. The pattern and magnitude of the secretory responses to TRH and GnRH were similar in depressed and diabetic patients. When the effects of GnRH and TRH were restudied in the presence of pirenzepine, neither GnRH nor TRH enhanced the serum concentrations of GH in any patient. These data indicate that a muscarinic cholinergic mechanism is involved in the anomalous responses of GH to GnRH and TRH in diabetic men and in male patients affected by major depression.
Lack of diurnal rhythm of low molecular weight insulin-like growth factor binding protein in patients with Cushing's disease
Authors: Degerblad M. , Póvoa G. , Thorén M. , Wivall I.-L. , Hall K.
Published: December 2008

Abstract. A specific radioimmunoassay with antibodies raised against the 25 kD insulin-like growth factor binding protein (25 kD IGFBP) in amniotic fluid was used to measure levels of cross-reacting protein in human serum and plasma. Plasma samples collected continually at 20-min intervals during 24-h in 6 healthy adults revealed a distinct diurnal rhythm in the concentration of 25 kD IGFBP. The lowest levels (9–13 μg/l) were found between 13.00 and 24.00 h with a rise after midnight to maximum levels (23–71 μg/l) between 03.00 and 09.00 h. There was no relation between the patterns of GH and 25 kD IGFBP. In 3 patients with active Cushing's disease, the levels of 25 kD IGFBP in plasma samples collected during 12 h, 19.00–07.00 h, were generally low and without nocturnal variations. One of the patients studied after extirpation of a pituitary adenoma displayed a nocturnal rhythm with maximum levels of 25 kD IGFBP between 03.00 and 07.00 h. Eight patients treated with stereotactic pituitary irradiation owing to Cushing's disease also showed a distinct nocturnal increase of 25 kD IGFBP. The results indicate the existence of a diurnal rhythm of 25 kD IGFBP in adults. Further, low levels and lack of diurnal rhythm of 25 kD IGFBP are demonstrated in Cushing's disease.
Serum prolactin in uraemia: correlations between bioactivity and activity in two immunoassays
Authors: Smith Caroline R. , Butler Joan , Iggo Neil , Norman Michael R.
Published: December 2008

Abstract. The clinical significance of hyperprolactinaemia in uraemic patients is uncertain and discrepancies between immunoactivity and biological activity of serum hPRL have been reported. We have modified the Nb2 cell bioassay to improve specificity for hPRL and used this assay to measure hPRL bioactivity in sera from 26 uraemic patients and 40 control subjects. Seventeen patients were receiving regular haemodialysis and 9 continuous ambulatory peritoneal dialysis. Levels of hPRL bioactivity were compared with hPRL immunoactivity measured by RIA (PRL-RIA) and by immunoradiometric assay (PRL-IRMA). Serum hPRL levels measured by all three assays were significantly elevated in uraemic patients compared with control subjects (P< 0.001). The immunoradiometric method gave significantly lower results than RIA in control subjects but not in uraemic patients (P< 0.05). There was no significant difference in mean ratio of hPRL bioactivity to PRL-RIA between patients and control subjects (1.18 ± 0.05 vs 1.11 ± 0.03, mean ± sem). The ratio of hPRL bioactivity to PRL-IRMA was slightly decreased in uraemic patients compared with controls (P = 0.05). Serum hPRL bioactivity was closely correlated with immunoactivity in both immunoassays (r ≥ 0.96) in patients and controls. These results confirm that elevated serum hPRL levels in uraemic patients represent biologically active hormone which may contribute to hypogonadism.
In vivo administration of a GnRH antagonist to male mice: effects on pituitary gonadotropin secretion in vitro
Authors: Gessel A. M. Ultee-van , van Steenbrugge G.J. , Leemborg F. G. , Schroeder F. H. , de Jong F. H.
Published: December 2008

Abstract. The potent luteinizing hormone-releasing hormone antagonist [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]GnRH (4 mg/kg) was administered sc once or daily for 21 days to immune-deficient (nude) and normal immune-competent (NIC) male mice derived from the same genetic background. Effects of in vivo pretreatment with the antagonist on gonadotropin secretion from hemipituitary glands from both types of mice were studied in vitro in the presence or absence of synthetic GnRH. Treatment with the GnRH antagonist caused differential effects on release of FSH and LH from and amounts of FSH and LH in hemipituitary glands. Pituitary FSH secretion was effectively inhibited, whereas effects on pituitary LH were less evident or nonsignificant under these experimental conditions. Long-term treatment with the antagonist caused larger effects on pituitary secretion and content of FSH, when compared with short-term treatment. No significant effects of duration of treatment on secretion or pituitary content of LH were detected. Addition of synthetic GnRH to the incubation medium caused stimulation of gonadotropin release. Therefore, it was concluded that the high doses of this GnRH antagonist were not able to block GnRH receptors effectively in the pituitary glands of nude and NIC male mice. The incomplete suppression of LH secretion by this high dose of the GnRH antagonist may partly explain the inability of the antagonist to suppress plasma testosterone levels and the growth of androgen-dependent tumours in male mice.
Two-monthly depot gonadotropin releasing hormone agonist (buserelin) for treatment of prostatic cancer
Authors: Waxman J. H. , Sandow J. , Abel P. , Farah N. , O'Donoghue E. P. N. , Fleming J. , Cox J. , Sikora K. , Williams G.
Published: December 2008

Abstract. The agonist analogues of gonadotropin-releasing hormone provide an alternate medical therapy for prostatic cancer. Current methods of administration of these analogues by daily injection or nasal spray is suboptimal in an elderly population. We have performed a pharmacological and endocrine evaluation of a new depot preparation of one such analogue, buserelin, active for 2 months. Thirty patients with advanced symptomatic prostatic cancer were treated. Serum testosterone was suppressed for the duration of treatment which ranged up to 14 months. The release characteristics of the depot were consistent and showed minimal variation between patients. This 2-month preparation of buserelin offers and advantage to the patient with prostatic cancer, over current treatment regimens.
Differential growth hormone responses to glucose and growth hormone releasing hormone in lactating dairy cows
Authors: Sartin J. L. , Pierce A. C. , Kemppainen R.J. , Bartol F. F. , Cummins K. A. , Marple D. N. , Williams J. C.
Published: December 2008

Abstract. Dairy cows in early lactation were reported to secrete growth hormone in response to declining glucose concentrations at day 5 but not day 30 post-partum, whereas GH responses to TRH were reported to be enhanced after day 30 post partum. The present study examined GH response following glucose infusion and the effect of GHRH as well as effects of SRIH on GHRH-stimulated GH release. Declining plasma glucose concentrations after glucose infusion stimulated GH release at day 5 post partum but not in nonpregnant, nonlactating cows or in cows at days 30 and 90 post partum. GHRH stimulated GH release on all days tested, but the response was highest at day 30 post partum when compared to other days. Somatostatin infusion inhibited GHRH effects on GH concentrations only at day 30 post partum and in nonpregnant, nonlactating cows. Thus, a differential response of the GH regulatory system could be demonstrated between days 5 and 30 post partum utilizing different stimuli. Evaluation of plasma glucose and free fatty acid concentrations on days 5, 10, 20, and 30 post partum revealed a progressive decrease in FFA but not glucose as lactation progressed. Decreased plasma FFA concentrations were paralleled by a decrease in basal GH, somatomedin-C and epinephrine. Thus, a decline in FFA may be responsible for the disparity between effects of GHRH and glucose on GH release between days 5 and 30 post partum.
Endocrine disturbances in suprasellar germinomas
Authors: Buchfelder M. , Fahlbusch R. , Walther M. , Mann K.
Published: December 2008

Abstract. The authors have investigated hypothalamicpituitary function in 8 patients (aged 9–27 years) with surgically and histologically proven suprasellar germinomas. Diabetes insipidus was found in 7 patients. All the patients had hypogonadism and hypocortisolism as judged by dynamic endocrine testing. Hypothyroidism was found in 6. Moreover, growth hormone secretion, as assessed by insulin-induced hypoglycemia, was defective in all patients. Comparison of results of insulin-induced hypoglycemia testing and stimulation tests by CRH and GHRH suggested that all patients had a primary supra-hypohypophyseal lesion rather than a primary pituitary defect. The authors conclude that suprasellar germinomas, although uncommon, should be included in the differential diagnosis of juvenile suprasellar tumours and in cases suggestive of idiopathic diabetes insipidus, even if neuroradiological investigation fails to demonstrate a discrete tumour.
Effects of acute insulin deficiency on catecholamine and indoleamine content and catecholamine turnover in microdissected hypothalamic nuclei in streptozotocin-diabetic rats
Authors: Oliver E. H. , Sartin J. L. , Dieberg G. , Rahe C. H. , Marple D. N. , Kemppainen R.J.
Published: December 2008

Abstract. The effects of streptozotocin-induced diabetes on catecholamine and indoleamine concentrations and catecholamine turnover rates in individual microdissected hypothalamic nuclei known, or believed, to be involved in the control of neuroendocrine function, were examined in control, insulin-treated diabetic and acutely insulin-withdrawn diabetic female rats. Streptozotocin-induced diabetes and acute insulin deficiency were demonstrated to result in increased concentrations of epinephrine in the suprachiasmatic nucleus, decreased turnover of epinephrine in the arcuate nucleus and decreased turnover of dopamine in the ventromedial nucleus was found to be increased in the insulin-treated diabetic animals. These data indicate that experimental diabetes and acute insulin deficiency result in the rapid onset of detectable alterations in epinephrine and dopamine activity in specific hypothalamic nuclei. These diabetes-induced changes may cause, or contribute to, the development of secondary neuroendocrine abnormalities known to occur in the diabetic condition.
Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine
Authors: Stoneham Susanna
Published: December 2008

Abstract. Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 μmol/l DL-isoproterenol was inhibited markedly less by N6-(phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P < 0.01). Glucose uptake was more responsive to N6-(phenylisopropyl)adenosine in adipocytes from control than treated animals (P < 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 ± 279 and 1988 ± 575 fmol/mg protein; mean ± sem). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) α subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6-(phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment.
Prepubertal treatment of rats with clomiphene citrate affects postpubertal testicular development
Authors: Brown Janine L. , Chakraborty Prabir K.
Published: December 2008

Abstract. A previous study showed that clomiphene citrate (clomiphene) reduced serum and pituitary gonadotropins and impaired testis growth and steroidogenesis in 10-day-old rats treated for up to two weeks. The present study was conducted to assess the effect of prepubertal clomiphene treatment on postpubertal pituitary-testicular function. Rats were implanted with pellets that released 0, 0.05, 0.5 or 5.0 mg clomiphene ·kg−1·day−1 between 10–31 days of age and were killed at 90 days of age. Testis and prostate weights in treated rats were reduced (P< 0.05), whereas serum LH, FSH and testosterone, and pituitary gonadotropin and GnRH receptor concentrations had recovered to levels observed in control rats. Testicular FSH receptor concentrations were not altered; however, FSH receptor content was decreased (P< 0.05) in clomiphene-treated rats proportional to the reduction in testicular weight. In contrast, testicular LH and GnRH receptor concentrations were increased (P< 0.05) in treated animals, resulting in similar receptor contents. Daily sperm production per gram of parenchyma was unaffected, while daily sperm production per testis was decreased in treated rats (P< 0.05). These data show early postnatal treatment with clomiphene does not permanently impair pituitary function. Despite reduced testicular mass, normal serum testosterone concentrations and testis LH receptor content of treated rats suggest recovered Leydig cell function. The decreased content of testicular FSH receptors and reduced sperm production suggest seminiferous tubule function was compromised in the adult rat.
Daily illuminance levels affect pituitary prolactin in male rats
Authors: Laakso Maija-Liisa , Porkka-Heiskanen Tarja , Alila Aino , Kajander Susanna , Stenberg Dag , Johansson Gunnar
Published: December 2008

Abstract. The 24-h patterns of melatonin, PRL, and gonadotropins in male rats maintained under natural lighting conditions have been found to differ from the patterns in rats kept under artificial lighting. In the present experiments we studied the role of different daily illuminances as a possible causative factor for the variation of the hormonal patterns. Three groups of male rats were kept under artificial lighting conditions (12 h on/12 h off), where the daily illuminance was 550, 110 or 25 lux. After a 7-day adaptation period the pineal content of melatonin, the serum levels of LH, FSH and PRL, and the pituitary content of these hormones were measured by RIAs in samples taken at 10.00, 13.00, 22.00 and 01.00 h. The patterns of pineal melatonin were equal in all three groups. The variation of daily illuminance did not change the serum levels of LH, FSH and PRL or the pituitary content of the gonadotropins. However, the pituitary content of PRL during the light phase was inversely related to the illuminance. The results suggest that the intensity of daily lighting in the studied range does not affect the patterns of melatonin or gonadotropins, but the synthesis of prolactin may be significantly regulated by the daily illuminance level.
Clobazam increases pulsatile luteinizing hormone secretion in normal men
Authors: Thomas G. , Thalabard J. C. , Duet M. , Girre C. , Fournier P. E.
Published: December 2008

Abstract. To investigate the effects of the 1,5-benzodiazepine, clobazam, on LH secretion in normal men, LH pulsatile secretion was defined after oral administration of 40 mg of clobazam or a placebo to 6 healthy male volunteers, according to a randomized cross-over design. LH pulse frequency increased significantly from a mean of 3.8 (range 3–5 pulses/8 h after placebo, to a mean of 5 (range 4–7) pulses/8 h (P< 0.05), after clobazam. Mean LH concentrations and peak amplitudes did not change significantly. These results suggest that clobazam mediates its effects on LH secretion at the hypothalamic level by increasing the frequency of episodic GnRH release.
A transplantable rat Leydig cell tumour. Properties of the prostaglandin E receptor
Authors: Erichsen Aage , Hansson Vidar
Published: December 2008

Abstract. In the present paper we have examined the properties of the prostaglandin E (PGE) receptor in a transplantable rat Leydig cell tumour (H-540). It appears that PGE1 and PGE2 share a common receptor in membrane particles from this Leydig cell tumour. From saturation analysis and modified Hofstee plots, the specific binding sites for PGE1 can be divided into a high (25%) and low affinity state (75%) with apparent equilibrium constants of dissociation (Kd) of 2.4 · 10−7 mol/l and 4.4 · 10−6 mol/l, respectively. Association rate kinetics at different temperatures employing 5 10−9 mol/l [3H]PGE1 showed that specific binding was time- and temperature-dependent. At 37°C an apparent steady state was achieved after approximately 4 h incubation. The binding of [3H]PGE1 was very tight and no dissociation was observed at 20°C during the first 20 h. The free PGE1 receptor appears to be very unstable. Binding was reduced rapidly by storage at 0°C, by freezing and thawing of membrane particles, and by incubation of concentrated membrane particles. Specificity curves showed that PGA1 and PGA2 displaced [3H]PGE1 from receptor to a somewhat lesser degree than PGE2 and PGE1, whereas PGs of the B, D, I and F series had little or no effect. The fact that inhibition of [3H] PGE1 binding by cold PGE1 occurred in the same concentration range as PGE1 activation of adenylate cyclase, indicates that the specific binding of PGE observed here represents functional receptors coupled to the adenylate cyclase.
The effect of sexual activity on androgen metabolism, androgen-receptor translocation, and glandular weight of ventral prostates of rats
Authors: Huang J. K. , Chang L. S. , Ho D. M. , Ho L. T.
Published: December 2008

Abstract. The present study was conducted to determine whether sexual activity exerts an effect on the action of androgen in the rat prostate. Eight-week-old Sprague-Dawley male rats were divided into two groups. Rats were grouped with female rats (sexualactive), or male (sexual-inactive) rats, and sacrificed 6 months later, The ventral prostates were dissected, homogenized and processed into cytosol and nuclei fractions. Testosterone and dihydrotestosterone were quantified by radioimmunoassay, and androgen receptor was determined by 'exchange assay' with radioactive methyltrienolone incubated for 18 h at 15°C. The main result were: 1) The steroid levels of testosterone and dihydrotestosterone in plasma and in the cytosolic fraction of prostate showed no significant difference between the two group of rats. 2) The prostatic nuclear dihydrotestosterone concentration of the sexual-active group (4.3 ± 0.83 pmol/mg DNA, N = 6) was significantly higher (P< 0.01) than that of the sexual-inactive group (1.68 ± 0.43, N = 6). 3) The androgen receptor was significantly higher (P< 0.05) in nuclear extract (0.64 ± 0.11 pmol/mg DNA, N = 6) and significantly lower (P< 0.01) in cytosol (53.4 ± 5.7 fmol/mg protein, N = 6) of the sexual-active group than those of the sexual inactive group (0.42 ± 0.13, N = 6 and 74.6 ± 11.8, N = 6, respectively). 4) In the sexual-active group, prostatic DNA content (3.82 ± 0.52 mg DNA/g tissue, N = 12) and prostatic weight (631 ± 122 mg, N = 29) was significantly greater (P< 0.05 and P< 0.01, respectively) than in the sexual-inactive group (2.82 ± 1.30, N = 15 and 514 ± 132, N = 40). It is suggested that the sexually experienced rats have significantly heavier prostates, which is associated with a higher concentration of dihydrotestosterone and androgen receptor in the nuclei.
Inhibin production by porcine granulosa and luteal cells: development and biological validation of a RIA
Authors: Michel U. , Jarry H. , Metten M. , Wuttke W.
Published: December 2008

Abstract. We describe the development and biological validation of a radioimmunoassay for immuno- and bioactive porcine inhibin. A synthetic 1-32 porcine inhibin peptide was used to raise an antiserum and Tyr-1-32 peptide as tracer. As standard we employed porcine follicular fluid calibrated with the 1-32 α-inhibin. Medium obtained from serum-free cultured porcine granulosa cells was chromatographed on Superose S-12 and Mono-Q. Resulting fractions were analysed for inhibin bio- and immunoreactivity. It is shown that granulosa cells produce at least two types of bioactive inhibins, one being also immunoactive in our RIA. We studied secretion of immunoreactive inhibin from porcine ovarian cells under various conditions: Inhibin secretion from mature and immature granulosa cells can be stimulated by FSH, whereas hCG enhances inhibin secretion only from mature granulosa cells. During extended time of culture, the capability of granulosa cells to secrete inhibin is reduced. In contrast, progesterone secretion from these cells increases; this is due to spontaneous functional luteinization. This assumption is supported by the low inhibin secretion of luteal cells in comparison to granulosa cells. Intracellular inhibin content in luteal cells is below detection limit of the RIA, whereas granulosa cells contain readily detectable amounts of this hormone.
Involvement of histaminergic neurons in the stress-induced release of pro-opiomelanocortin-derived peptides in rats
Authors: Knigge Ulrich , Matzen Steen , Bach Flemming W. , Bang Peter , Warberg Jørgen
Published: December 2008

Abstract. Histamine, which acts as a neurotransmitter, stimulates the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin, and β-endorphin. Since stress affects the hypothalamic turn-over of neuronal histamine, we investigated the role of histaminergic neurons in the mediation of the stress-induced release of ACTH and β-endorphin immunoreactivity in male rats. In control animals histamine receptor antagonists had no effect on the release of ACTH or β-endorphin immunoreactivity. Restraint and ether stress increased plasma ACTH 3- and 2-fold, respectively. The responses were almost prevented by intracerebroventricular or intra-arterial infusion of the H2-receptor antagonists cimetidine and ranitidine. Infused intracerebroventricularly the H1-receptor antagonist mepyramine inhibited the ACTH response to restraint by 45% (P< 0.01), but had no effect on the response to ether. Infused intra-arterially the H1-receptor antagonists mepyramine or SKF-93944 had no effect. Restraint and ether stress increased plasma β-endorphin immunoreactivity 6- and 5-fold, respectively. Sephadex G-50 gel chromatography of plasma showed that the β-endorphin immunoreactivity in stressed rats coeluted with β-lipotropin and β-endorphin, whereas the immunoreactivity in control animals co-eluted almost exclusively with β-endorphin. The H2-receptor antagonists cimetidine and ranitidine infused intracerebroventricurlarly inhibited the responses of β-endorphin immunoreactivity to restraint and ether stress by 90 and 70%, respectively, whereas intra-arterial infusion of these antagonists inhibited the responses by only 50 and 60%, respectively. The H1-receptor antagonist mepyramine infused intracerebroventricularly inhibited the β-endorphin immunoreactivity response to restraint and ether stress by 40 and 25%, respectively, whereas intra-arterial infusion of mepyramine or the other H1-receptor antagonist SKF-93944 prevented the response to restraint stress, but had no effect on the response to ether stress. We suggest that hypothalamic histamine is involved in the mediation of the stress-induced release of the proopiomelanocortin-derived peptides ACTH, β-endorphin and β-lipotropin. The effect is mediated preferentially via H2-receptors, but H1-receptors may also play a role.
Effect of pinealectomy on the undernutrition-induced suppression of the reproductive axis in rats
Authors: Chik Constance L. , Ho Anthony K. , Brown Gregory M.
Published: December 2008

Abstract. Food restriction is known to sensitize the reproductive axis of rats to the inhibitory action of the pineal gland and its hormone, melatonin. The present study investigated the effect of pinealectomy on the undernutrition-related reproductive suppresion. Three groups of animals (control, sham pinealectomy or pinealectomy) were subjected to either 3 weeks of 50% food restriction or ad libitum feeding under a lighting regimen of 14 h light and 10 h dark. At the end of the treatment period, body weight, testes weight, accessory organ weights, serum LH and serum testosterone were determined. In the pinealectomized animals, accessory organ weights and serum testosterone levels increased significantly. As compared to the controls, underfed pinealectomized animals had a partial recovery of the reduced accessory organ weights and normalization of the serum testosterone levels. These findings suggests that pinealectomy has a protective effect on the gonads of both control and underfed animals and that underfed animals are more sensitive to this protective mechanism.
Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children
Authors: Ghigo Ezio , Goffi Stefania , Mazza Enrico , Arvat Emanuela , Procopio Massimo , Bellone Jaele , Müller Eugenio E. , Camanni Franco
Published: December 2008

Abstract. In normal adults, repeated GHRH administration leads to progressively decreasing somatotrope responses. To verify whether this GH secretory pattern also connotes normal growing children, we have studied the effects of two consecutive (every 120 min) 1 μg/kg iv GHRH boluses on GH release in normal adults (N = 7, age 23.2–30.6 years) children (N = 6, age 10.4–13.2 years). In the adults, the GH response to the second GHRH bolus (peak, mean ± sem: 2.9 ± 0.8 μg/l) was lower (P< 0.02) than that to the first bolus (15.9 ± 2.4 μg/l). Conversely, in children the GH response to the second GHRH bolus (25.6 ± 6.3 μg/l) overrode the first one (13.6 ± 6.5 μg/l), but this difference did not attain statistical significance. In adults cholinergic enhancement by pyridostigmine, a cholinesterase inhibitor, was previously shown to re-instate, even to potentiate somatotrope responsiveness to consecutive GHRH boluses. Thus, in 5 children GH response to repeated GHRH boluses was retested administering pyridostigmine (60 mg orally) 30 min before the second GHRH bolus. In these subjects, pyridostigmine failed significantly to potentiate the GH responsiveness to the second GHRH bolus (30.3 ± 4.6 vs 25.0 ± 7.6 μg/l). These data indicate that differently from in adults, in children repeated GHRH administration does not reduce somatotrope responsiveness and that cholinergic enhancement fails to potentiate GH responsiveness to the second GHRH bolus.
T lymphocyte activation in euthyroid Graves' ophthalmopathy: soluble interleukin 2 receptor release, cellular interleukin 2 receptor expression and interleukin 2 production
Authors: Lai Kar Neng , Leung Joseph C. K. , Chow Chun Chung , Cockram Clive S.
Published: December 2008

Abstract. The present study was undertaken to examine the cellular control arm of the immune response with regard to T lymphocyte proliferation in euthyroid Graves' ophthalmopathy. Twenty patients with euthyroid Graves' ophthalmopathy (7 on antithyroid drugs and 13 on no treatment) and 18 healthy controls were studied in an infection-free period. Mitogen-stimulated cellular interleukin 2 (IL2) receptor expression, soluble interleukin 2 receptor release, and interleukin 2 production, were studied in peripheral blood mononuclear cells cultured for 24 h. The cellular IL2 receptor expression and soluble IL2 receptor release did not differ between the patients and healthy controls. In contrast, IL2 production in response to pokeweed mitogen stimulation was increased in lymphocytes from patients with Graves' ophthalmopathy. The IL2 release did not correlate with the quantities of cellular and soluble IL2 receptor. The mitogen-stimulated cellular IL2 receptor expression, IL2 receptor release, and IL2 production did not differ between patients with or without carbimazole therapy. Despite a suggested role of autoreactive T cells in mediating the development and propagation of autoimmune thyroid disease, this study fails to demonstrate a defective T lymphocyte activation state in patients with Graves' ophthalmopathy during an euthyroid state.
Impaired glucagon secretion to insulin-induced hypoglycemia in anorexia nervosa
Authors: Fujii Shinichi , Tamai Hajime , Kumai Mitsuharu , Takaichi Yukihiko , Nakagawa Tetsuya , Aoki Thomas T.
Published: December 2008

Abstract. In order to clarify the role played by pancreatic α-cell dysfunction in the impaired glucose recovery from hypoglycemia in patients with anorexia nervosa, the response of pancreatic α-cells to insulin-induced hypoglycemia was investigated in 16 patients with anorexia nervosa before and after treatment. The results were compared with those obtained after loading with arginine. Before treatment, despite comparable falls in plasma glucose levels, glucagon secretion was significantly reduced in the anorectic patients compared with control subjects. In addition, glucose recovery from hypoglycemia in the patients was attenuated. However, after treatment, both glucagon secretory activity and plasma glucose recovery following insulin-induced hypoglycemia were restored to normal. Plasma glucagon responses to arginine infusion were not significantly different in the untreated anorectic patients and control subjects. However, the plasma insulin response in the patients was significantly lower than in the control group. These results suggest that the impaired recovery of plasma glucose levels from insulin-induced hypoglycemia in patients with anorexia nervosa is primarily attributable to impaired pancreatic α-secretory capability. In addition, this abnormality in pancreatic α-cell function is reversible with treatment leading to improved nutrition and weight gain.