bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of pharmacological doses of calcitonin on serum osteocalcin concentration in patients with Paget's disease of the bone
Authors: Mulder H. , Schop C. , Koster J. C.
Published: December 2008

Abstract. The effect of continuous infusion of calcitonin on serum osteocalcin concentration was studied in 14 patients with Paget's disease. In all patients serum osteocalcin was initially increased. Within 24 h calcitonin gradually reduced serum osteocalcin, a marker of osteoblastic activity. This means that inhibition of the function of the osteoclasts by calcitonin results in an inhibition of the osteoblasts within 24 h in patients with Paget's disease.
Insulin-like growth factor I responses to recombinant bovine growth hormone during feed restriction in heifers
Authors: Ronge H. , Blum J.
Published: December 2008

Abstract. Insulin-like growth factor I, other hormones and blood metabolites were measured in growing heifers before, during and after a 3-day period of normal feed intake and a corresponding period of reduced feed intake. In addition, 0.1 or 0.5 mg recombinant bovine GH/kg was injected daily for 5 days during normal or during and following reduced feed intake. During reduced feed intake blood concentrations of insulin-like growth factor I, insulin, T4, T3, glucose and urea-nitrogen decreased, whereas those of non-esterified fatty acids, albumin and protein increased (P< 0.05). GH, insulin-like growth factor I and insulin increased, whereas urea-nitrogen decreased in response to exogenous GH when heifers were adequately fed (P< 0.05). In contrast, insulin-like growth factor I did not change during GH injections while heifers received reduced amounts of feed. Therefore, during insufficient energy and (or) protein intake, characterized by low glucose, insulin and thyroid hormone levels and increased non-esterified fatty acid concentrations, insulin-like growth factor I concentrations and responses to GH administration were markedly reduced.
Administration of a GnRH-antagonist to immature rats affects subsequent female and male pubertal development differently
Authors: van den Dungen H. M. , van Dieten J. A. M. J. , Tilders F. J. H. , van Rees G. P. , Schoemaker J.
Published: December 2008

Abstract. Gonadotropin secretion was inhibited in immature male and female rats by sc administration of the GnRH-antagonist ORG30276 (GnRH-A) on days 6, 9, 12 and 15. In GnRH-A-treated females this resulted in suppression of the temporarily increased plasma LH and FSH levels, which normally occur in prepubertal female rats. Ovarian weight was decreased. Although vaginal opening in GnRH-A-treated rats occurred earlier, the age of 1st estrus and the number of ova shed at first ovulation were not affected. Fertility at 4 months of age was normal. After initial suppression of gonadotropin levels, the FSH levels in GnRH-A-treated males, however, sharply increased to about twice the control levels. Plasma FSH remained elevated at least until 4 months of age. The LH levels at adult age were not affected by antagonist treatment and neither were testosterone levels. Testicular weight was decreased by GnRH-A from about 50% on day 15 to about 30% at 4 months of age. Pubertal development as measured by balano-preputial separation was delayed by about 7–10 days. At 4 months of age fertility was decreased. Thus, suppression of early gonadotropin secretion by GnRH-A treatment had dramatic effects on subsequent pubertal development in the male, but not in the female rat.
Plasma GHRH, CRH, ACTH, β-endorphin, human placental lactogen, GH and cortisol concentrations at the third trimester of pregnancy
Authors: Jeske W. , Soszyński P. , Rogoziński W. , Lukaszewicz E. , Latoszewska W. , Snochowska H.
Published: December 2008

Abstract. The aim of the study was to determine the concentration of GHRH and CRH in maternal plasma during the 3rd trimester of pregnancy and to search for the possible correlations with related hormones such as ACTH, β-endorphin, cortisol, GH and human placental lactogen. Patients consisted of 31 healthy pregnant women (20–39 years) divided according to duration of pregnancy into 2 groups: I. from 26 to 32 pregnancy week N = 13), II. from 33 to 39 week (N = 18), and of 7 women evaluated 3 days after delivery. All listed hormones except ACTH were measured by RIA (GHRH, CRH and β-endorphin-like immunoreactivity after extraction with silic acid) and ACTH by IRMA. In the late 3rd trimester plasma levels of CRH (P< 0.001), ACTH (P< 0.02), β-endorphin (P< 0.05), cortisol (P< 0.025), as well as GHRH (P< 0.002) and human placental lactogen (hPL) (P< 0.001) were increased in comparison to early 3rd trimester, whereas 3 days after delivery CRH and GHRH became undetectable and those of ACTH and cortisol decreased significantly. The CRH plasma concentrations were found to be strongly correlated with gestational age (r = 0.86, P< 0.001) but not with ACTH and cortisol. GHRH levels correlated mainly with human placental lactogen concentrations (r = 0.64, P< 0.001). Conclusion: In maternal plasma at the 3rd trimester of pregnancy, apart from the known markedly elevated CRH, the GHRH level was also raised. Strong correlations between CRH and gestational age and those between GHRH and human placental lactogen suggest that there is a relationship between these neurohormones and the placental function.
Increases in concentrations of somatostatin- and insulin-like immunoreactivities in submandibular salivary gland of diabetic rats: effect of insulin treatment
Authors: de Perière D. Deville , Hillaire-Buys D. , Gross R. , Puech R. , Arancibia S.
Published: December 2008

Abstract. To investigate whether systemic insulin levels can influence somatostatin-like immunoreactivity and insulin-like immunoreactivity concentrations in the rat submandibular salivary glands, we measured the concentrations of the two peptides in an experimental group rendered diabetic by streptozotocin administration. The diabetic group showed a low plasma level of insulin compared with the control group: 0.5 ± 0.1 vs 3.5 ± 0.8 μg/l, (P< 0.01). Concomitantly, they exhibited clear glucosuria and a blood glucose level which was four times higher than in normal animals: 35.5 ± 1.4 vs 8.8 ± 0.8 mmol/l, (P< 0.001). The two peptide concentrations in the submandibular glands of diabetic rats showed an increase compared with controls: 42.9 ± 4.7 protein vs 24.7 ± 3.1 pg/mg protein (P< 0.001) and 34.9 ± 4.9 protein vs 18.4 ± 4.0 pg/mg protein (P< for insulin-like immunoreactivity concentration and somatostatin-like immunoreactivity concentration, respectively. Chronic insulin treatment of diabetic rats reversed the increase in somatostatin, but had no effect on the increase in insulinlike immunoreactivity concentration. A negative correlation (r = 0.24, P< 0.05) was found between the plasma insulin level and the somatostatin concentration of the submandibular glands. Our results suggest that the submandibular glands of rats may participate in the peripheral regulation of glucose homeostasis.
The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency
Authors: Toublanc Jean Edmond , Couprie Claire , Garnier Philippe , Job Jean-Claude
Published: December 2008

Abstract. The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below −2 sd in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of a reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1–2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.
The effect of thyroxine, 3,5-dimethyl-3'-isopropyl-L-thyronine and iodized oil on fetal brain development in the iodine-deficient sheep
Authors: Mano M. T. , Potter B.J. , Belling G. B. , Martin D. M. , Gragg B. G. , Chavadej J. , Hetzel B. S.
Published: December 2008

Studies have been carried out to investigate the role of maternal and fetal thyroid function in the effects of iodine deficiency on fetal brain development in sheep. Iodine deficiency was established with an especially prepared low-iodine diet of maize and pea pollard. The iodine-deficient sheep were mated and at the end of the second trimester of pregnancy (100 days gestation) were divided into groups which received either a sc injection of T4 or 3,5-dimethyl-3'-isopropyl-L-thyronine or an im injection of iodized oil. At 140 days gestation (10 days prior to parturition) comparison of the fetuses delivered by hysterotomy revealed that the retarded fetal brain development observed in iodine deficiency was greatly improved by T4 and by iodized oil. However, T4 and iodized oil failed to correct the reduction in the number and the increase in the length of synaptic appositions which were observed in the fetal cerebral cortex after iodine deficiency. In addition, the histological appearance of the fetal thyroid gland and the levels of plasma thyroid hormones were restored to normal. The administration of 3,5-dimethyl-3'-isopropyl-L-thyronine had no effect on the retarded fetal brain and body development of the iodine-deficient fetuses. The lack of response may be due to the inability of 3,5-dimethyl-3'-isopropyl-L-thyronine to cross the ovine placenta as no reduction in the abnormally elevated fetal plasma TSH was observed in spite of a fall in maternal plasma TSH and apparent restoration of maternal thyroid function. It is concluded that the retarded fetal brain development observed during iodine deficiency in sheep can be substantially improved by iodized oil or to a lesser extent by T4 administration at 100 days gestation and that this is dependent on the restoration of both maternal and fetal thyroid function which supports previous observations from this laboratory following fetal and maternal thyroidectomy. The persistence of some effects of iodine deficiency on the fetal brain suggests that irreversible damage may have occurred.
Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects
Authors: Paolisso G. , Passariello N. , Pizza G. , Marrazzo G. , Giunta R. , Sgambato S. , Varricchio M. , D'Onofrio F.
Published: December 2008

Hypomagnesemia and low erythrocyte magnesium content are both common findings in non-insulin-dependent diabetic subjects. Moreover, intracellular magnesium may play a crucial role in modulating B-cell response to glucose by interfering with potassium permeability. Eight elderly, moderately obese, non-insulin-dependent diabetic subjects were treated with either magnesium supplementation (3 g/day) to the diet or placebo. Both treatment schemes lasted 4 weeks and were separated by a 'wash-out' of 3 weeks. At the end of each treatment period, an iv glucose tolerance test (0.33 g/kg for 3 min) and an iv arginine (5 g) test were performed to determine the B- and A-cell responses. Dietary magnesium supplementation vs placebo produced a slight but significant decrease in basal plasma glucose (8.6 ± 0.3 vs 8.0 ± 0.1 mmol/l, p < 0.05) and an increase in acute insulin response after iv glucose (37.1 ± 2.3 vs −14.7 ±0.9 pmol · 1−1 · (10 min)−1, p < 0.01) and after iv arginine (151 ± 22 vs 81 ± 15 pmol · 1−1 · (10 min)−1, p < 0.01), respectively. Plasma glucagon levels were unaffected by chronic dietary magnesium supplementation as well under basal conditions as in response to arginine. Net increase in acute insulin response after iv glucose and after iv arginine was significantly correlated to the net increase in erythrocyte magnesium content after dietary magnesium supplementation. We conclude that magnesium administration may be a useful adjuvant to the classic hypoglycemic agents in the treatment of non-insulin-dependent diabetic subjects.
Serum levels of vitamin D metabolites in the elderly
Authors: Aksnes Lage , Rødland Ole , Ødegaard Ole R. , Bakke Kåre J. , Aarskog Dagfinn
Published: December 2008

The serum concentrations of 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D-binding protein, PTH and calcitonin were measured in three groups of elderly Norwegian subjects (age 70–96 years): active elderly living at home, warded geriatric patients not supplemented with vitamin D, and warded geriatric patients supplemented with a daily dose of 400 IU vitamin D2. The results were compared with the concentrations of vitamin D metabolites found in a group of young and middle-aged adults (age 22–59 years). Decreased serum concentrations of 25-dihydroxyvitamin D3 were found in all groups of elderly compared with younger adults. Active elderly living at home had higher concentrations of 25-dihydroxyvitamin D3 than geriatric ward patients. Supplementation of geriatric ward patients with 400 IU vitamin D2 resulted in an increase in the median serum 25-dihydroxyvitamin D concentration by about 30 nmol/l. Decreased median concentration of 1,25-dihydroxyvitamin D was found in geriatric ward patients not supplemented with vitamin D, indicating that this group is at risk of vitamin D deficiency. The active elderly living at home and the warded geriatric patients receiving vitamin D supplementation had normal median concentrations of 1,25-dihydroxyvitamin D, indicating that nephrogenous synthesis of 1,25-dihydroxyvitamin D is not generally impaired in the elderly, and that a moderate vitamin D supplementation may correct low 1,25-dihydroxyvitamin D levels owing to vitamin D deficiency. However, the serum concentrations of 1,25-dihydroxyvitamin D showed great individual variations. No significant differences were observed for vitamin D-binding protein, 'free-1,25-dihydroxyvitamin D' or PTH between the groups. The median serum concentrations of 24,25-dihydroxyvitamin D were significantly lower in all three groups of elderly compared with the younger adults.
Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin®)
Authors: Stehouwer C. D. A. , Lems W. F. , Fischer H. R. A. , Hackeng W. H. L. , Naafs M. A. B.
Published: December 2008

Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin analogue octreotide (Sandostatin®) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and glucoregulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.
Human serum LH inhibitor(s): behaviour and contribution to in vitro bioassay of LH using dispersed mouse Leydig cells
Authors: Ding Ying-Qing , Huhtaniemi Ilpo
Published: December 2008

The present study aimed at investigating the nature and causes of non-parallelism in testosterone responses to serial dilutions of peripheral serum and standard LH preparations in the mouse Leydig cell in vitro bioassay of LH. Immunoadsorption with monoclonal antibody to the β-subunit of LH was used to obtain LH-free serum; the procedure removed more than 98% of the immunoassayable LH. When a constant amount of the LH-free serum was added to standard dilutions, the bioassay dose-response curves to serum dilutions and standards became parallel, i.e. the well-known source of error of this assay system was eliminated. When standard curves prepared in medium and LH-free serum (final concentration 10%) were compared, no effect of the serum was found on basal cAMP and testosterone production. However, the LH-stimulated testosterone and cAMP production were suppressed by serum by a rather constant factor of 40%. Mild heating (60°C, 15 min) or treatment with dextran-coated charcoal, but not ether extraction, was able to eliminate the inhibitory activity of the LH-free serum. Binding studies demonstrated that [125I]hCG interaction with mouse Leydig cell homogenates was inhibited by LH-free serum in a fashion indicative of reduced LH receptor number, but not of reduced binding affinity. In conclusion, these data show that human serum contains LH inhibitor(s) which affect the LH-receptor interaction and LH stimulated testosterone production in mouse Leydig cell in vitro. The effect is marked in serum concentration over 1.5% and it shows only minor variation between individual sera. This source of error can be effectively removed from the LH in vitro bioassay by using LH-free serum for preparation of dilutions of LH standards.
Human antral fluid IGF-I and oocyte maturity: effect of stimulation therapy
Authors: Roussie M. , Royère D. , Guillonueau M. , Lansac J. , Muh J. P.
Published: December 2008

Studies in animals have highlighted a possible role for growth factors, particularly IGF-I on cellular replication and cytodifferentiation in the ovary. At this time, few studies have been performed about IGF-I in the human ovary. From 38 women undergoing in Vitro Fertilization 293 antral fluids were collected and assessed for steroids (estradiol and progesterone), FSH and IGF-I. Two induction treatments were compared: clomiphene citrate/hMG (group A, N = 15), triptoreline/hMG (group B, N = 23). We also studied relationships between quantitative parameters and oocyte collection or oocyte corona cumulus complex maturity. In group B, the highest antral estradiol levels were found in follicles yielding an oocyte (p <0.05). Concerning antral progesterone, higher levels were observed in follicles collected from group A than in follicles collected from group B (p < 0.05); for this parameter, the highest levels were observed when an oocyte was harvested, whatever the treatment (p <0.05). Highest antral FSH levels were observed in group B (p <0.05). IGF-I levels were higher in follicles collected from group B than in follicles collected from group A (p <0.05) and antral IGF-I levels differed between mature and immature oocyte corona cumulus complex in group B (p <0.05). These results, which are in keeping with studies about biological action of IGF-I in animal or human follicles or granulosa cells, led us to hypothesize a role for IGF-I in human follicular recruitment and maturation, a role that possibly is enhanced during GnRH analogue and gonadotropin therapy.
Effects of thyroid hormones on cartilage sulphation in sex-linked dwarf chickens
Authors: Hoshino S. , Wakita M. , Kobayashi Y. , Kakegawa T. , Suzuki M.
Published: December 2008

The present investigation was undertaken to see if exogenous thyroid hormone could stimulate cartilage sulphation in vivo and in vitro in sex-linked dwarf chickens. L-thyroxine or L-3,5,3'-triiodothyronine injection for 7 consecutive days stimulated in vivo 35SO2−4 incorporation into trachea cartilages of the dwarf chicken. Both thyroid hormones added to the incubation medium with or without 2.5% dwarf chicken serum also stimulated in vitro 35SO2−4 incorporation into pelvic rudiment from 11-day chick embryos. These data demonstrate that thyroid hormones, like insulin-like growth factor I, might be responsible for the reduced growth rate of dwarf chickens.
Does prolonged dopaminergic blockade alter the LH pulsatile secretion in normal cycling and postmenopausal women?
Authors: Rossmanith Winfried G. , Wirth Ulrike , Yen Samuel S. C.
Published: December 2008

To investigate effects of prolonged dopaminergic antagonism on LH pulsatile secretion, 22 normal cycling women (10 in the early follicular phase (days 3 and 4), 6 in the late follicular phase (days 10 to 13), 6 in the midluteal phase (days 6 to 8 after ovulations)) and 8 postmenopausal women were studied before and during 8-h dopamine receptor blockade imposed by metoclopramide. Sequential 8-h infusions of either saline (50 ml/h) or metoclopramide (30 μg · kg−1 · h−1) were conducted on two consecutive days. LH pulsatile activity was assessed in blood samples obtained at 15 min intervals during these 8-h infusion periods. Basal estradiol and progesterone concentrations were lowest (p <0.001) in postmenopausal and highest (p <0.001) in the midluteal phase women, 8-h metoclopramide infusions evoked prompt (within 90 min, p <0.001) and sustained (> 70 μg/1, p < 0.001) increases of PRL, similar (p = 0.78)) in magnitude for normal cycling and postmenopausal women. Metoclopramide infusions failed to significantly modify the LH pulsatile acitivity during the menstrual cycles and in hypogonadal women. These observations suggest that even in the presence of high circulating estradiol and progesterone concentrations the dopaminergic inhibition may not be operating. However, any possible stimulatory effect on LH secretion by dopamine receptor blockade may be confounded by the concomitant metoclopramide-induced hyperprolactinemia.
Serum thyroglobulin during the menstrual cycle, during pregnancy, and post partum
Authors: Rasmussen Nini G. , Hornnes Peter J. , Hegedüs Laszlo , Feldt-Rasmussen Ulla
Published: December 2008

Serum thyroglobulin, TSH, thyroid hormones and thyroid volume were investigated during the menstrual cycle in 10 healthy females (day 2, 9, 16, 23 and day 2 of next cycle), during pregnancy (week 18, 24, 30 and 36) and post partum (1, 2, 3, 6 and 12 months) in 20 healthy females. During the menstrual cycle median serum thyroglobulin increased from 27 (day 2) to 32 μg/l (day 23, p < 0.01 ). Serum TSH and thyroid volume demonstrated a similar increase with a positive correlation between serum thyroglobulin and thyroid volume (r = 0.65, p < 0.02). Median serum thyroglobulin was significantly increased during the whole pregnancy (week 36, 73 μg/l) compared with post partum (1 month post partum, 22 μg/l, p < 0.01), as was thyroid volume. Serum TSH was unaltered and free thyroid hormone indices decreased during pregnancy compared with post partum. No relation between changes in serum thyroglobulin and thyroid volume, TSH or thyroid hormones could be demonstrated. Serum thyroglobulin alterations thus were related to alterations in TSH and thyroid volume during the menstrual cycle. However, the increase in serum thyroglobulin and thyroid volume during pregnancy were unrelated to changes in serum TSH, indicating other mechanisms of regulation than TSH. When interpreting serum thyroglobulin levels in women, the co-existence of pregnancy and time of menstrual cycle should be taken into account in order to avoid misinterpretation of results.
A single dose of lithium carbonate acutely elevates intact parathyroid hormone levels in humans
Authors: Seely Ellen W. , Moore Thomas J. , LeBoff Meryl S. , Brown Edward M.
Published: December 2008

Hyperparathyroidism has been reported in patients receiving lithium therapy, and lithium alters calcium-regulated PTH release in vitro. Previous studies in vivo have used assays which measure fragments of PTH as well as the intact hormone. To determine if lithium acutely elevates intact PTH levels, we studied 9 subjects who received a single oral dose of lithium carbonate (600 mg). Serum levels of intact PTH, ionized calcium, and lithium were measured before, 2 and 14 h after the dose of lithium. PTH levels rose significantly 2 h following the dose of lithium (before 22 ± 5.0, post 32 ± 7.3 ng/l, p < 0.02). PTH levels had returned to baseline at 14 h (22 ± 3.8 ng/l). There were no significant changes in ionized calcium levels. Therefore, a single oral dose of lithium carbonate acutely elevates intact PTH values in human subjects.
In vitro effects of ketoconazole on corticotrope cell morphology and ACTH secretion of two pituitary adenomas removed from patients with Nelson's syndrome
Authors: Reina L.Jimenez , Leal-Cerro A. , Garcia J. , Garcia-Luna P.P. , Astorga R. , Bernal G.
Published: December 2008

The direct effects of ketoconazole on the secretion of ACTH by human pituitary adenoma cells from 2 patients with Nelson's syndrome were studied in vitro. Stereologically quantified, intracellular changes affect the surface density of the endoplasmic reticulum (it decreased by 73%), the volume density of the secretion granules (it decreased by 49%), and the volume density of lysosomes (it decreased by 67%). The hormone released in the culture medium decreased depending on the doses of ketoconazole used; 10 μmol/l decreased ACTH levels by 31%. These data show that ketoconazole induce marked changes on corticotrope morphology and ACTH secretion in pituitary cells obtained from patients with Nelson's syndrome.
A sensitive and practical bioassay for thyrotropin using cultured FRTL-5 cells: assessment of bioactivity for serum TSH in patients with chronic renal failure
Authors: Horimoto Masateru , Nishikawa Mitsushige , Yoshikawa Norio , Inada Mitsuo
Published: December 2008

A sensitive bioassay for TSH employing a practical extraction method was developed, and the bioactivities in patients with chronic renal failure receiving hemodialysis were compared with those in normal subjects. Serum samples were obtained from 12 normal subjects and 12 patients with chronic renal failure receiving hemodialysis. TSH was extracted from the serum using anti-human TSH monoclonal antibody coated tubes, followed by elution with 2.0 mol/l guanidine-HCl solution (pH 3.2). After the eluate had been dialyzed against phosphate buffered saline (pH 7.4) and again against TRIS-HCl solution (pH 7.4) and then lyophilized, it was reconstituted with hypotonic Hanks' solution. Bioassay for TSH was performed by measuring the levels of cAMP released into the medium from cultured FRTL-5 cells incubated with the extract. The mean immunoreactive recovery rates of TSH from the serum in normal subjects and patients with chronic renal failure were about 42% (± 6) and 40% (± 2), respectively. The present bioassay was sufficiently sensitive to detect a serum TSH level of 1.0 mU/l when 3.0 ml of serum was used. Extracts from standard sera at concentrations ranging from 1.0 to 10 mU/l added to the culture medium caused significant linear increases in cAMP production. Based on analysis of covariance the regression line between the immunoreactivities and bioactivities of serum TSH in patients with chronic renal failure (y = 0.90x + 0.3, r = 0.92) was not significantly different from that in normal subjects (y = 1.04x + 0.1, r = 0.93). These results suggest that the present bioassay for TSH is sensitive and practical, and that the bioactivity of TSH in patients with chronic renal failure is similar to that in normal subjects.
Inhibition of insulin degradation by insulin-like growth factors I and II in human hepatoma (HepG2) cells
Authors: Keller Susanne , Schmid Christoph , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

IGF-I infused at pharmacological doses in healthy men markedly decreases C-peptide levels, whereas insulin levels remain within the normal range. One possible explanation is decreased insulin removal. As the liver is the major site of insulin degradation, we studied insulin degradation by HepG2 cells in the presence of IGF. We found that IGF-I at a concentration of 130 nmol/l inhibits insulin degradation by HepG2 cells when the initial insulin concentration is 0.34 nmol/l. The effect of IGF-I on insulin degradation is dose-dependent and the rate of insulin degradation is dependent on the insulin concentration. IGF-II is 6 to 10 times more potent than IGF-I in inhibiting 125I-insulin binding to HepG2 cells and in protecting insulin from being degraded. Thus, IGF-I and IGF-II inhibit insulin degradation most likely by competing for binding at insulin binding sites of liver cells.
Determination of prolactin, growth hormone, β-endorphin, and cortisol in both maternal plasma and amniotic fluid during human gestation
Authors: Kubota Toshiro , Tsuzuki Hiroo , Saito Motoi
Published: December 2008

This study focuses on PRL, GH, β-endorphin and cortisol in maternal blood and amniotic fluid during human pregnancy. Maternal blood and amniotic fluid samples were obtained from 18 normal pregnant women in the second trimester, 12 full-term gravidas having spontaneous delivery, and 10 full-term gravidas having elective cesarean section. Two gravidas bearing anencephalic fetuses in the third trimester were also studied. In the second trimester women, levels of PRL (3215.9 ± 458.9 μg/l), GH (19.1 ± 1.7 μg/l) and β-endorphin (11.1 ± 0.9 pmol/l) were significantly higher in the amniotic fluid than in maternal plasma. In addition, PRL was significantly correlated with β-endorphin (r = 0.670) and with GH (r = 0.547) in the amniotic fluid. However, amniotic fluid cortisol levels (0.27 ± 0.18 nmol/l) were significantly lower than plasma cortisol levels. The amniotic fluid of the women with anencephalic fetuses had normal levels of PRL, GH and β-endorphin. In full-term gravidas, plasma PRL levels were significantly lower in women with vaginal delivery than in those with elective cesarean section, and there was a significant negative correlation between plasma PRL and β-endorphin, and between plasma PRL and cortisol levels. Plasma GH levels in women with vaginal delivery showed no signficant difference from those in women with cesarean section. Examination of amniotic fluid yielded no significant differences in the levels of PRL, β-endorphin and GH between these two groups. The authors conclude that the hormone releasing system in amniotic fluid seems to be independent of that in maternal plasma during pregnancy, and that the stress of labour has a significant effect on plasma PRL, β-endorphin and cortisol levels in maternal plasma but not on those in amniotic fluid.
Increased activity of ovarian thecal cytochrome P45017α in the hamster induced by endogenous LH
Authors: Johnson Donald C. , Sen Mitra
Published: December 2008

The in vivo regulatory action of LH on the ovarian androgen synthesizing enzyme cytochrome P45017α (17α-hydroxylase/C17, 20-lyase) was studied in cyclic golden hamsters. Immunohistochemical studies using anti-porcine testicular cytochrome P45017α antibody indicated that the enzyme was limited to thecal cells. Transient removal of the negative feedback action of endogenous steroids by use of aminoglutethimide phosphate produced an increase in endogenous gonadotropins. A single dose (30 mg) of aminoglutethimide on days 1, 2 or 3 of the estrous cycle (day 1 = estrus), increased serum levels of LH, but only for about 12 h. Increases in enzyme activities, which persisted for at least 24 h, followed. Two doses of aminoglutethimide, 12 h apart, maintained elevated levels of serum LH for about 36 h, and enzyme activites for at least 48 h. However, when the drug was given after the pre-ovulatory surge of LH on proestrus, and again on the morning of estrus, neither serum LH nor enzyme activity levels increased within 24 h. Induced increases in enzyme activity had no effect upon ovulation rate, as determined by the number of oviductal eggs present on the morning of estrus. The results demonstrate clearly a close correlation between serum concentrations of LH and ovarian androgen synthesizing enzyme activity.
Direct administration of testosterone increases rat tibial epiphyseal growth plate width
Authors: Ren Song Guang , Malozowski Saul , Sanchez Prosper , Sweet Donald E. , Loriaux D. Lynn , Cassorla Fernando
Published: December 2008

Local injection of hormones into the tibial epiphyseal growth plate offers a possible model to answer whether sex steroids can affect bone growth directly. To answer this question, we injected different doses of testosterone enanthate (4, 40, 120 and 400 μg/100 g of rat weight) once into the tibial epiphyseal growth plate of castrated 35-day-old male rats. The contralateral tibia was injected with sesame oil and served as control. All animals were sacrificed at age 42 days. Tibias were removed for measurement of epiphyseal growth plate width and blood was collected for measurement of serum IGF-I and testosterone. The lower doses of testosterone enanthate (4, 40 and 120 μg/100 g) did not produce any significant change in epiphyseal growth plate width. Testosterone at the largest dose tested (400 μg/100 g) increased epiphyseal growth plate width by about 15% compared to control (p < 0.01). At this dose, serum testosterone was not increased, suggesting that the effect on epiphyseal growth plate width was not due to higher systemic testosterone concentrations. No differences in IGF-I levels were observed among the groups. We conclude that direct administration of testosterone enanthate at a dose of 400 μg/100 g into the rat tibial epiphyseal growth plate can increase epiphyseal growth plate width.
Influence of rifampicin on thyroid gland volume, thyroid hormones, and antipyrine metabolism
Authors: Christensen Hanne R. , Simonsen Kim , Hegedüs Laszlo , Hansen Bo M. , Døssing Martin , Kampmann Jens P. , Hansen Jens M.
Published: December 2008

The influence of rifampicin (450 mg/day for 28 days) on the hepatic microsomal enzymes and thyroid function variables were investigated in 13 healthy male volunteers. After 14 and 28 days of treatment a significant increase in median thyroid volume (determined ultrasonically) was demonstrated (20 ml, range 13–28 before; 26 ml, range 18–48 at day 14, and 24 ml, range 17–40 at day 28) (p <0.01). A significant decrease in median serum free T4 index levels was seen (94.1 arbitrary units, range 80.1–123.4 before treatment; 86.8, range 71.7–102.0 at day 14, and 85.3, range 65.5–131.3 at day 28) (p <0.01). Serum T4, T3, T3 resin uptake, free T3 index and TSH levels were not significantly altered. Hepatic microsomal enzyme activity assessed by antipyrine clearance was significantly increased (approximately by 85%) at day 14 and 28, whereafter it normalized. The study supports the hypothesis that the increase in thyroid volume after treatment with rifampicin and other hepatic enzyme system inducers (e.g. phenytoin and carbamazepine) is a compensatory mechanism caused by an increased hepatic degradation of thyroid hormones.
Acute facilitory action of progesterone on gonadotropin secretion of perifused rat pituitary cells
Authors: Ortmann Olaf , Wiese Huberta , Knuppen Rudolf , Emons Günter
Published: December 2008

The purpose of this study was to investigate the kinetics and estrogen dependence of the facilitory progesterone action on LH and FSH secretion from pituitary cells under dynamic culture conditions. Anterior pituitary cells obtained from ovariectomized or intact adult Wistar rats were cultivated on Cytodex 1 microcarrier beads. The perifusion experiments were performed with four separate perifusion chambers. The cells of chambers I+II had been pretreated with medium containing vehicle (0.1% ethanol), those of chambers III + IV with medium containing 1 nmol/l estradiol for 48 h. After perifusion was started, each of the chambers was challenged with an initial 2-min GnRH (1 nmol/l) pulse. Chamber I was further perifused with medium containing vehicle, chamber II with medium containing vehicle + 100 nmol/l progesterone, chamber III with medium containing 1 nmol/l estradiol, and chamber IV with medium containing 1 nmol/l estradiol + 100 nmol/l progesterone. Three further GnRH pulses were administered at 50-min intervals to each of the chambers. In estradiolprimed cells from intact rats, progesterone induced a positive effect on LH and FSH secretion after 50 min of exposure to progesterone. After 100 min of progesterone treatment, LH and FSH release were enhanced to 420 and 500 per cent, respectively. When such cells were not primed with estradiol, a slight though insignificant positive action of progesterone on LH release was present after 50 and 100 min of treatment, whereas FSH secretion was not influenced. The facilitory effect of progesterone occurred only after 100 min when estradiol-primed cells from ovariectomized rats were used. LH and FSH secretion were only enhanced by up to 210 and 233 per cent, respectively. When these cells were not primed with estradiol the positive progesterone effect was absent. In conclusion, progesterone induces an acute facilitory effect on GnRH-induced LH and FSH secretion which is estrogen-dependent.
In vivo responsiveness to glucocorticoid correlated with glucocorticoid receptor content in peripheral blood leukocytes in normal humans
Authors: Tanaka Hirotoshi , Ichikawa Yoichi , Akama Hideto , Homma Mitsuo
Published: December 2008

Dexamethasone loading tests (0.1 mg dexamethasone/kg, iv) were performed in 18 normal males to evaluate the individual responsiveness to glucocorticoid. There were inter-individual differences in increase in peripheral blood polymorphonuclear leukocyte count, decrease in peripheral blood lymphocyte count, and increase in plasma free fatty acids levels after dexamethasone injection. In addition, there was a significant correlation between the maximum increase in polymorphonuclear leukocytes and the maximum decrease in lymphocytes (r = 0.7514, p < 0.0003). Simultaneous measurements of glucocorticoid receptor content by whole-cell assay revealed that glucocorticoid receptor content in polymorphonuclear leukocytes linearly correlated with that in the corresponding lymphocytes (r = 0.9482, p < 0.0001). There were also significant correlations between the maximum increase in polymorphonuclear leukocytes and glucocorticoid receptor content in polymorphonuclear leukocytes (r = 0.7239, p < 0.0007), and between the maximum decrease in lymphocytes and glucocorticoid receptor content in lymphocytes (r = 0.7703, p < 0.0002). These results suggest that individual differences are preserved both in glucocorticoid responsiveness and in glucocorticoid receptor content in peripheral blood leukocytes in normal humans.
The stimulated C-kinase activity in estradiol-treated rat pituitaries is reduced by chronic treatment with the dopamine agonist CV 205-502
Authors: Birman P. , Touraine Ph. , Bai-Grenier F. , Dubray C. , Kaabache T. , Peillon F. , Joubert (Bression) D.
Published: December 2008

To investigate whether the modulation of lactotrope cell multiplication and prolactin secretion in rat pituitary glands implicated the phosphoinositide C-kinase system, female Wistar rats were treated or not with the dopamine agonist CV 205-502 or 8 days or with estradiol cervical implants for 8 for 15 days, alone or in combination with CV 205-502 for the last 8 days. CV 205-502 treatment induced a significant reduction in plasma PRL levels and in pituitary weights, whereas estradiol treatment induced a significant increase in both parameters. CV 205-502, in association with estradiol, counteracted estradiol stimulation of PRL levels and of pituitary weights. Total C-kinase activity in controls was 29.8 ± 9.9 pmol 32phosphorus/min (N = 7, mean±sem), mainly found in the soluble fraction (84%). When administered alone, CV 205-502 induced a significant reduction (–58%, p < 0.02) in C-kinase activity in the particulate fraction with no modification in the soluble fraction. Both 8 and 15 days estradiol treatment induced a significant stimulation of total C-kinase activity, 74% and 155% respectively. When combined with estradiol, CV 205-502 significantly (p < 0.02) counteracted the estradiol increase in total C-kinase activity, which was only 45% over control values. We conclude that treatment with a dopamine agonist and estradiol, which have antagonistic effects on the pituitary, exerts an opposite regulation of C-kinase activity. Whether this may be one of the mechanisms involved in their interaction on pituitary lactotropes remains to be determined.
Effect of congenital renal disease and neonatal thyroid status on urinary human epidermal growth factor concentrations
Authors: Scott Susan M. , Guardian Carmela , Rogers Cathy , Angelus Pam , Werner Sher
Published: December 2008

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen. In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.
On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas
Authors: Hermansen Kjeld , Yanaihara Noboru , Ahrén Bo
Published: December 2008

Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2–29 (by 75 ± 4%), like the native galanin1–29 (by 90 ± 3%) potently inhibited insulin secretion (p < 0.001). In contrast, galanin3–29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin 10–29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1–15 significantly inhibited insulin secretion (by 24 ± 5%; p < 0.01), though with a lower potency than did native galanin (p < 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p < 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion. The removal of the N-terminal Gly residue decreases the action of galanin on insulin secretion to a much smaller extent than does the removal of, in addition, the Trp residue. However, the remainder of the molecule seems necessary for full potency. It is also concluded that the inhibition by galanin of somatostatin secretion seems to require the entire molecule.
Sn-1,2-diacylglycerols and phorbol ester stimulate the production of progesterone from the human placenta
Authors: Kato Hiromi , Kato Masayuki , Kasugai Masahide , Mizutani Sigehiko , Ninagawa Terumi , Tomoda Yutaka
Published: December 2008

Human term placental explants were used to investigate the possible role of phospholipid-sensitive and Ca2+ dependent protein kinase in the regulation of human placental progesterone production. Placental tissue was incubated with low density lipoprotein as a precursor of progesterone in the presence or the absence of phorbol 12-myristate-13-acetate, 1-oleoyl-2-acetyl-glycerol, and the calcium ionophore A23187. The rate of progesterone production by placental tissue was 21.7 ± 4.6 ng · (mg wet wt)−1 · (2 h)−1 (mean ± sem) with 500 mg low density lipoprotein/1 (control). The rate of progesterone production was accelerated 2-fold by l nmol/1 phorbol 12-myristate-13-acetate, 1.6-fold by 250 μmol/1 1-oleoyl-2-acetyl-glycerol and this increase was dose-related (25–250 μmol/1 1-oleoyl-2-acetyl-glycerol). A non-promoting derivative, 4α-phorbol-12,13-didecanoate had no effect. The phorbol 12-myristate-13-acetate or 1-oleoyl-2-acetyl-glycerol induced stimulation of progesterone production was not associated with a change in the intracellular cAMP level. Addition of 10 μmol/1 A23187 further increased progesterone production with 125 μmol/1 1-oleoyl-2-acetyl-glycerol. The rate of progesterone production was accelerated 1.6-fold by 125 μmol/1 1-oleoyl-2-acetyl-glycerol and 10 μmol/1 A23187 as compared with control. The effects of the phorbol ester and the diacyl glycerol were completely blocked by the addition of the protein synthesis inhibitor cycloheximide. We conclude that these phorbol regents are able to stimulate human placental progesterone production. The possible roles of intracellular Ca2+ and protein kinase C in placental steroidogenesis are discussed.
Infusion of atrial natriuretic hormone in DOCA/salt and spontaneously hypertensive rats
Authors: Fujimura Akio , Kyker Kimberly D. , Kem David C.
Published: December 2008

The effects of a 6-day infusion of atrial natriuretic hormone (ANH) on blood pressure and urinary sodium excretion were determined in conscious DOCA/salt and spontaneously hypertensive rats. The DOCA/salt rats were randomly divided into two groups after 4 weeks and either infused by osmotic minipump with 32.5 pmol/h of ANH in 0.1 % gelatin vehicle or sham operated with emplacement of a blind cannula. Thirteen-week-old spontaneously hypertensive rats were studied in a similar fashion. The baseline systolic blood pressure prior to the infusion was 176 ± 7 mmHg (x ± sem) in the ANH group and 169±5 mmHg in the sham group of DOCA/salt animals. The ANH infusion in the DOCA/salt animals dropped their blood pressure to 160 ± 10 mmHg (p < 0.01) compared to that in the sham controls which continued to rise to 200 ± 7 mmHg. The blood pressure response to ANH infusion in the spontaneously hypertensive rats was slightly greater, with a blood pressure of 192 ± 5 mmHg in the sham group and 132 ± 3 mmHg in the ANH-infused animals. ANH infusion produces a qualitatively similar blood pressure response in the DOCA/salt rat as well as the other hypertensive models. This response is relatively less on a quantitative basis than that observed in the spontaneously hypertensive rats and is not related to changes in sodium balance or volume contraction.