bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique
Authors: Arslanian Silva , Kalhan Satish
Published: June 2009

The effect of growth hormone releasing hormone (GHRH-44) therapy on insulin action and secretion was evaluated in a hypopituitary patient after one month and one year of treatment. Hepatic and peripheral insulin action was studied with the hyperinsulinemic-euglycemic clamp in combination with [6,6-2H2]glucose tracer infusion. First and second phase insulin secretion was assessed with the hyperglycemic clamp. Prior to GHRH-44 therapy the hypopituitary patient had higher insulin mediated glucose disposal rate and lower basal and stimulated insulin concentrations by more than two standard deviations from the mean of a control group. Following therapy there was no change in basal hepatic glucose production; however, there was evidence of diminished peripheral insulin action. This was manifested by decreased insulin mediated glucose disposal during the hyperinsulinemic-euglycemic clamp, and increased insulin secretion during the hyperglycemic clamp. We conclude that GHRH-44 therapy in this patient was associated with decreased peripheral insulin action which was compensated for by increased insulin secretion.
Conversion from pure 17,20-desmolase- to combined 17,20-desmolase/17α-hydroxylase deficiency with age
Authors: Zachmann Milo , Kempken Bianca , Manella Brigitte , Navarro Elizabeth
Published: June 2009

A previously described phenotypically female 46,XY-individual with 1 7,20-desmolase deficiency was followed from adolescence to adulthood. While at age 16.9 years her 1 7α-hydroxylating capacity was normal and steroids not hydroxylated in position 17 low, decreasing 1 7α-hydroxylated and increasing unhydroxylated steroids were observed thereafter up to the age of 25.2 years. Simultaneously with the steroid changes, previously normal blood pressure (110/80 mmHg) increased (180/130 mmHg). Since 17α-hydroxylation and 17,20-desmolase activity are regulated by one cytochrome P450-17α, it is concluded that, in this same patient, 1 7α-hydroxylase activity was normal during childhood and adolescence, but decreased in the young adult. 1 7,20-desmolase activity, by contrast, was completely absent already in the fetus, causing absence of masculinization. The factors modulating this difference in cytochrome P450-17α activity with age are as yet unknown.
Time-dependent effect of hyperglycemia and hyperinsulinemia on oxidative and non-oxidative glucose metabolism in patients with NIDDM
Authors: Franssila-Kallunki Anja I , Eriksson Johan G , Groop Leif C
Published: June 2009

The present study was undertaken to compare the effect of hyperglycemia and euglycemia during identical hyperinsulinemic conditions on glucose metabolism in NIDDM subjects. Eight NIDDM subjects participated in a 4 h hyperglycemic (12.1±0.7 mmol/l), hyperinsulinemic (475±43 pmol/l) and in a 4 h euglycemic (5.5±0.5 mmol/l), hyperinsulinemic (468±36 pmol/l) insulin clamp in combination with indirect calorimetry and [3H]-3-glucose. Six non-diabetic subjects were studied during euglycemia (5.1±0.2 mmol/l) and hyperinsulinemia (474±35 pmol/l) and served as controls. In NIDDM patients the rate of insulin-stimulated glucose disposal was 57% greater during hyperglycemia compared with euglycemia throughout the 4 h clamp (p<0.01). The major part of the increase in glucose metabolism during hyperglycemia was due to an increase in the non-oxidative glucose metabolism (89%). Whereas glucose metabolism could not be normalized during the prolonged euglycemic hyperinsulinemic clamp in NIDDM patients (49.9±6.8 vs 57.5±5.4 μmol·(kgLBM)−1·min−1 in controls) the addition of hyperglycemia resulted in complete normalization of the glucose disposal rates (78.3±5.8 μmol·(kgLBM)−1·min−1). The effect of hyperglycemia was apparent already at 60 min of the clamp. The data thus suggest that glucose metabolism in NIDDM is insulin resistant, but that the defect in insulin-stimulated glucose uptake can be overcome by increasing the glucose concentration.
The expression of insulin-like growth factor binding proteins is tissue specific during human fetal life and early infancy
Authors: Funk Barbara , Kessler Ulrike , Eisenmenger Wolfgang , Hansmann Angela , Kolb Helmut J , Kiess Wieland
Published: June 2009

The insulin-like growth factors (IGFs) are bound to multiple IGF binding proteins (IGFBPs) that are present both in the circulation and in extracellular fluids. There are at least six different IGFBP species that have been fully characterized in terms of molecular structure and amino acid sequence. The tissue distribution and local production of these proteins as well as the regulation of IGFBP production in different tissues have not been elucidated. We have studied the distribution of multiple IGFBP species in protein extracts from human kidney, skeletal muscle, lung, liver and brain by ligand blotting employing [125I]IGF-2 as the radiolabeled hormone. Five distinct IGFBP species with a respective molecular weight of43, 38, 34, 30 and 20 kDa were detected on the ligand blots in tissues from human fetuses and infants (23 weeks of gestation till 24 months of postnatal age). The 34 kDa species and a 30–32 kDa IGFBP species were predominant in brain, whereas a 30 kDa IGFBP species was mainly detected in skeletal muscle. Immunoblotting experiments using an anti IGFBP-2 antiserum showed that the 34 kDa IGFBP species from human brain was presumably related to IGFBP-2. We conclude that IGFBPs are differentially expressed in different tissues throughout human fetal life and early infancy. Local production or accumulation of the different IGFBPs could modulate IGF action at a local level or alternatively have differential functions during development.
Reversible menopause induced by the GnRH analogue buserelin: effects on lipoprotein metabolism
Authors: Farish Elizabeth , Fletcher Colin D , Barnes Judith F , Mack Ann , Gray Christina E , Hart David M
Published: June 2009

GnRH agonists can induce a reversible pharmacological menopause and can be used to treat endometriosis, a fairly common gynaecological problem which responds well to oestrogen deprivation. Premature menopause is associated with adverse lipid changes and an increased risk of coronary heart disease. Therefore we set out to investigate changes in lipoprotein metabolism in a group of premenopausal women being treated with the GnRH analogue buserelin for active endometriosis. We monitored lipoprotein levels, high density lipoprotein subfractions and apolipoproteins AI, AII and B during a 12-month course of treatment and for 6 months afterwards. Treatment caused a sustained increase in HDL3 cholesterol levels and a small increase in low density lipoprotein cholesterol, which was significant at the six-month visit only. Apolipoprotein B levels rose significantly and there were marginal increases in apolipoproteins AI and AII. All changes and trends were reversed after cessation of treatment. We conclude that the treatment did not profoundly affect lipoprotein metabolism, neither LDL nor HDL cholesterol, the established important risk markers for coronary heart disease appreciably altered.
The pituitary-gonadal axis in women with benign or malignant ovarian tumors
Authors: Blaakaer Jan , Djursing Henning , Hørding Ulla , Bennett Paul , Toftager-Larsen Kim , Bock Johannes E , Lebech Paul E
Published: June 2009

The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione, testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were investigated prior to surgery in 24 postmenopausal women with benign and 28 postmenopausal women with malignant epithelial ovarian tumors. The serum concentrations of hormones were compared with those of 28 healthy, postmenopausal, age-matched controls. Significantly lower serum FSH levels were demonstrated in women with malignant tumors. No significant differences were found between the groups regarding the serum LH levels. The hCG levels were low in all groups. Regarding progesterone and estradiol levels, low postmenopausal steroid levels were found in all groups examined and no significant differences were demonstrated within the groups. No significant correlations between the levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude a central depression of gonadotropin release mediated by the dopaminergic system we examined the thyroid stimulating hormone (TSH) and prolactin. No differences were found between the groups regarding TSH and prolactin levels. A possible relationship between other hormones/factors produced by the tumor and exerting a negative feedback, either centrally or directly, on the gonadotropin release remains to be investigated. A change in biological activity in the gonadotropins might explain the present findings.
Direct effect of ACTH on renin release in isolated perfused guinea-pig kidneys with adrenal glands
Authors: Hu Hong-Yi , Mokuda Osamu , Sakamoto Yoshikazu , Shimizu Naokata
Published: June 2009

To investigate the direct effect of corticotropin (ACTH) on the renin-angiotensin-aldosterone system, isolated guinea-pig kidneys with adrenal glands were perfused with various doses of ACTH (0.1–1000 μg/l) and 0.3 mmol/l of dibutyryl cyclic AMP (cAMP) through each cannula inserted into the abdominal aorta and the inferior caval vein. Perfusate renin activity was increased in a dose-dependent manner by the addition of ACTH in a range of 0.1–1000 μg/l, and reached a plateau at 20 min with each dose. The perfusate cAMP level was dose-dependently increased with 10–1000 μg/l of ACTH. Perfusate renin activity was also markedly increased by the addition of dibutyryl cAMP. The same effects of ACTH on renin and cAMP secretions were observed in the kidney perfusion model from which the adrenal glands were excluded. Aldosterone secretion failed to respond to 0.1 μg/l of ACTH, and was increased by higher concentrations (1–1000 μg/1) in the same experiments. These results demonstrate that ACTH has a direct effect on renal renin release in a physiological concentration (0.1 μg/l), and that the action of ACTH is probably mediated by cAMP. The sensitivity of renin release to ACTH stimulation is no less than that of aldosterone secretion during ACTH infusion, so it is possible that ACTH is an important stimulator of the renin-angiotensin system.
Concurrent adrenocortical carcinoma and Conn's adenoma in a man with primary hyperaldosteronism. In vivo and in vitro studies
Authors: Touitou Y , Boissonnas A , Bogdan A , Auzéby A
Published: June 2009

This is a report of a rare and unusual case of adrenal pathology. A patient presented with clinical and biological signs of primary aldosteronism and computed body tomography scan led to our suspecting the presence of a left adrenocortical carcinoma. The in vitro studies performed on the resected tumour showed very low synthesis of mineralocorticoids and glucocorticoids. The patient could not be re-examined until 15 months later, when he still suffered hypertension; another tomography scan revealed a mass on the right adrenal gland. The studies performed on this second tumour confirmed the diagnosis of Conn's adenoma: active in vitro biosynthesis of 18-hydroxy-corticosterone and aldosterone from exogenous tritiated precursors.
Corticotropin-releasing hormone in health and disease: an update
Authors: Ur Ehud , Grossman Ashley
Published: June 2009

Corticotropin-releasing hormone (CRH) was initially sequenced and identified in 1981, and has since become established as the principal organizer of the stress response. It causes activation of the pituitary-adrenal axis, behavioural arousal, sympathetic stimulation and a decrease in appetite. In vitro studies have shown regulation of hypothalamic CRH by a variety of neuro-transmitters, including the cytokines interleukin-1 and interleukin-6. However, circulating CRH is mainly derived from extra-hypothalamic sites, and levels may be elevated in patients with tumours secreting ectopic CRH. The placenta is a further source of CRH, which may be specifically raised in patients with pre-eclampsia, and could be a factor in the initiation of parturition. The recently identified CRH binding protein may play a vital role in this process. Clinically, CRH testing has become extremely useful in the diagnosis and differential diagnosis of Cushing's syndrome, and particularly for the localization of ACTH following inferior petrosal sinus catheterization. There is considerable evidence that many patients with depressive illness may have a disturbance of the central control of CRH, and this may be become of increasing importance in the therapy of this common condition. There are also intriguing new data suggesting that abnormalities in CRH regulation may be involved in the pathogenesis of inflammatory arthritis.
Effects of corticotropin-releasing hormone on the postoperative course of elderly patients under long-term artificial respiration
Authors: Nink M , Beyer J , Krause U , Holzhauer F , Junginger Th , Lehnert H
Published: June 2009

In both human and animal studies a stimulatory effect of corticotropin-releasing hormone (CRH) on respiration and on cognitive parameters has been demonstrated. Our own studies employing human CRH (hCRH) iv in healthy volunteers and different groups of patients have shown hCRH to be a safe drug. We prospectively studied the clinical effects of a standardized dose of 100 μg hCRH iv in 12 elderly patients following major abdominal surgery who remained comatose and were under prolonged respirator therapy over a mean period of 37 days. Cardio-respiratory parameters, blood gas values, plasma cortisol and catecholamines were evaluated before and 30 min following hCRH injection. Furthermore, vigilance was tested using a score system. Ventilation was markedly enhanced following hCRH injection while the cardiovascular parameters were only moderately affected. Vigilance was augmented in all subjects and improved impressively in five patients. The changes were of great benefit for the patients treated and supported their respirator weaning procedures and mobilization training.
The effect of a met-enkephalin analogue on growth hormone, prolactin, gonadotropins, cortisol and thyroid stimulating hormone in healthy elderly men
Authors: Giusti M , Delitala G , Marini G , Uggias B , Sessarego P , Besser GM , Grossman A , Giordano G
Published: June 2009

The aim of the study was to evaluate the effect of the guanyl derivative of the opioid analogue D-ala2,MePhe4-Met-enkephalin-(o)-ol (G-DAMME) on pituitary secretion in healthy elderly men. Nine healthy elderly men (65–88 years) and 10 young adults (20–30 years) were studied. GH, PRL, gonadotropins, cortisol (to evaluate the effect on ACTH) and TSH were measured after G-DAMME (0.25 mg iv) or placebo administration. In elderly men, the GH response to G-DAMME was reduced or absent, while prompt GH release was found in all young men. G-DAMME lowered LH levels in young men but not in elderly men. No significant variations in FSH levels after G-DAMME and placebo were noted in either group of subjects. A similar and significant rise in PRL and TSH, and a fall in cortisol, after G-DAMME was observed in both elderly and young adults. We have demonstrated that the sensitivity to opioid modulation by G-DAMME on PRL, TSH and cortisol secretion is unchanged with aging. On the other hand, the data indicate that LH and GH responsiveness to G-DAMME change with age.
A monthly cycle in the plasma concentration of GnRH and the glomerular filtered load of GnRH during second trimester pregnancy
Authors: Paaby Per O , Nielsen Aage , Raffn Kjeld
Published: June 2009

Six healthy women were examined three times a week during the second trimester. The aim of the study was to test the existence of a monthly cycle in plasma GnRH. Because the kidney plays a dominant part in the elimination of small peptides from the circulation by filtration, the filtered load (P-GnRH × GFR) of GnRH was estimated and tested for a cycle. A mathematical model (parabolas overlaid with a cosine curve and containing parameters for cycle length, cycle amplitude and phase) was used in a multivariate analysis of changes in plasma GnRH, creatinine clearance and GnRH filtered load. We found significant monthly cycles in plasma GnRH (p = 0.003) and in GnRH filtered load (p = 0.004), but no significance for a cycle in creatinine clearance. As an intermediate result we demonstrated that the tubular reabsorption of GnRH was unsaturated for all values of plasma GnRH and GnRH filtered load in question. The increased pregnancy level of plasma GnRH originates in part in the placenta, but we assume that the cycle generator is contained in the maternal neuroendocrine system.
The hypothalamo-pituitary regulation of androgen secretion in young men after prolonged physical stress combined with energy and sleep deprivation
Authors: Opstad Per Kristian
Published: June 2009

During a five days' military training course for male cadets with hard physical activity day and night and almost no sleep or food, a decrease was found in LH, FSH, PRL and TSH. A decrease was also found in testosterone, dihydrotestosterone (DHT), androstenedione, dehydroepiandrosterone and 17α-OH progesterone, whereas dehydroepiandrosterone-sulfate increased twofold. The LH and FSH responses to GnRH intravenously were increased at the end of the course. This demonstrates enhanced pituitary reserves of gonadotropin, or, alternatively, increased sensitivity to GnRH stimulation and may be due to decreased hypothalamic secretion of GnRH during the course. The decreased DHT and testosterone levels were almost normalized after HCG stimulation, indicating a gonadotropin regulated decrease in testosterone secretion during the course. In spite of fairly weak correlation between the alteration in gonadotropins and androgens it is concluded that there is a major regulation of testicular androgen secretion during prolonged stress by the hypothalamo-pituitary axis.
Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children
Authors: Angioni Stefano , Iori Gabriella , Cellini Monica , Sardelli Silvia , Massolo Fausta , Petraglia Felice , Genazzani Andrea R
Published: June 2009

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of β-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N= 8). β-interferon (1 000 000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (− 15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following β-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, β-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and β-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that β-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.
Interrelationships between urinary sodium, calcium, hydroxyproline and serum PTH in healthy subjects
Authors: Chan Ellen LP , Ho Chung Shun , MacDonald Dorothy , Ho Suzanne C , Chan Thomas YK , Swaminathan R
Published: June 2009

The effect of sodium intake on the excretion of calcium, hydroxyproline (OHP) and serum parathyroid hormone (PTH) was examined. When seven healthy males increased their sodium intake by 200 mmol/day, excretion of calcium increased by 1.70 mmol/day and that of OHP by 27%. Serum PTH, however, did not increase significantly. In a cross-sectional study of 334 healthy female subjects there were strong positive correlations between fasting urinary sodium/creatinine (Na/Cr) and calcium/creatinine (Ca/Cr) ratios (r=0.573) and between Na/Cr and urinary OHP/Cr ratios (r=0.246). Serum PTH was negatively correlated with Na/Cr ratio (r= −0.161). We conclude that an increase in dietary sodium causes calciuria and an increase in hydroxyproline excretion. The results do not support the hypothesis that this is mediated by PTH.
Possible involvement of leukotrienes in human luteal function
Authors: Yoshimura Yasunori , Nakamura Yukio , Ichikawa Fumitaka , Oda Takahisa , Jinno Masao , Ando Motomu , Koyama Norihiro , Shiokawa Shigetatsu
Published: June 2009

The present study was undertaken to assess the ability of human corpora lutea to produce leukotriene B4 (LTB4). The maximum capacity of luteal cells to secrete progesterone was attained on day 4, and both the basal production and the responsiveness to hCG decreased thereafter. In contrast, the production of LTB4 by cultured luteal cells was significantly reduced on day 4, but increased thereafter. The basal concentration of LTB4 produced by luteal cells varied from 75 to 590 pg/105 cells/2 days. LTB4 production appeared to decrease concomitantly with increased-progesterone production in cultured luteal cells. Exposure to hCG decreased significantly LTB4 production by cultured luteal cells on day 4. An inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (NDGA), inhibited LTB4 production in a dose-dependent manner. However, NDGA did not affect basal progesterone production by the cultured luteal cells. A significant inverse relationship existed between the accumulation rates of progesterone and LTB4 in the luteal cells. Furthermore, the addition of LTB4 inhibited progesterone production in a dose-dependent manner in both the presence and absence of hCG. In conclusion, LTB4 could be synthesized by human corpora lutea in vitro, and correlated inversely with the secretion rates of progesterone. These data suggest that LTB4 produced locally in the corpus luteum may be an important regulator in human luteal regression.
Role of the antiglucocorticoid RU 486 in the prevention of steroid-induced hypertension
Authors: Opoku Justicia , Kalimi Mohammed
Published: June 2009

In the present study, we determined the effect of RU 486 on two experimental models of hypertension in the rat, deoxycorticosterone acetate (DOCA)-salt in nephrectomized rats and spontaneously hypertensive rats. Uni-nephrectomized saline-drinking male Sprague-Dawley rats were divided into three groups and each animal was given either 0.2ml olive oil (control), 1 mg DOCA, or 1 mg DOCA +10 mg RU 486 dissolved in 0.2 ml olive oil every third day for a period of three weeks. Within a week of steroid administration, there was a significant increase in the systolic blood pressure (SBP) in the DOCA-salt (157±3.8 mmHg) and DOCA+RU 486 (155±2.1 mmHg) treated rats over the control (116±2.6 mmHg) rats, which remained elevated throughout the experimental period. There was significant increase in the water intake and urine output in DOCA or DOCA+RU 486 treated rats as compared to the control untreated rats. In the experiment involving the spontaneously hypertensive rats, the rats were divided into three groups and each animal given 0.2 ml olive oil (control), 1 mg RU 486, or 5 mg RU 486 dissolved in 0.2 ml olive oil for six weeks. Instead of the expected decrease in the blood pressure, RU 486 significantly elevated blood pressure during the six weeks of drug administration. Water intake, urine output, and weights remained comparable in both groups. We conclude that RU 486 has no effect on the DOCA-salt model of hypertension but, surprisingly, elevates hypertension in the spontaneously hypertensive rats.
Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV activities in the mouse uterus and ovary
Authors: Ohta Naoshi , Takahashi Takayuki , Mori Takao , Park Min Kyun , Kawashima Seiichiro , Takahashi Kenji , Kobayashi Hideshi
Published: June 2009

Prolyl endopeptidase and dipeptidyl peptidase IV are proline-specific peptidases, and are ubiquitously distributed in various tissues in mammals. The specific activities of these peptidases in both uterus and ovary were examined in the SHN strain of mice at estrus or diestrus. A marked change in prolyl endopeptidase activity was found in the uterus and ovary in intact mice during the estrous cycle, the activity being high at estrus and low at diestrus. In ovariectomized mice, prolyl endopeptidase activity was significantly higher in the uterus treated with progesterone or estradiol than in the uterus treated with vehicle oil only or a dopamine antagonist (perphenazine) which stimulates prolactin secretion. On the other hand, notable change in dipeptidyl peptidase IV activity during the estrous cycle was found only in the uterus of intact mice. The activity was low at estrus and high at diestrus. In ovariectomized mice, the uterus exposed to estradiol showed a lower dipeptidyl peptidase IV activity than the uteri treated with progesterone, the dopamine antagonist or vehicle oil. These findings reveal that there is a close correlation between the circulating level of ovarian steroids and the activities of these prolinespecific enzymes.
Parathyroid hormone degradation by opossum kidney cells via receptor-mediated endocytosis and lysosomal hydrolysis
Authors: Yamaguchi Toru , Arao Makoto , Fukase Masaaki
Published: June 2009

The mechanisms involved in parathyroid hormone (PTH) degradation by proximal renal tubule cells were studied using an opossum kidney cell line possessing PTH receptors as an in vitro model system. One hour incubation of 5 nmol/l human (h) PTH-(1-84) with intact opossum kidney cells (4.0× 106 cells) resulted in about 70% degradation and disappearance of hPTH-(1-84) from the medium, as determined by a two-site immunoradiometric assay. Preincubation with 100 nmol/l h[Nle8, Nle18, Tyr34]PTH-(1-34)amide for 6, 24, 48 and 72 h caused a 26, 47, 62 and 73% decrease, respectively, in PTH degradation by opossum kidney cells. Binding studies with 125I-labeled h[Nle8, Nle18, Tyr34]PTH-(1-34)amide as a radioligand showed that PTH receptor binding decreased with the time of pretreatment with the agonist. Pretreatments of the cells with monensin, an inhibitor of endocytosis, and the lysosomotropic agents such as chloroquine, ammonium chloride and leupeptin, inhibited degradation of hPTH-(1-84) by 87, 71, 76 and 72%, respectively. Concentrations of 5 nmol/l hPTH-(39-84) and hPTH-(39-68), which are known not to bind to PTH receptors appreciably, were not degraded by opossum kidney cells during 1 h incubations. Thus intact, biologically active PTH, but not its inactive fragments, is degraded by opossum kidney cells, by receptor-mediated endocytosis and lysosomal hydrolysis. A mechanism resembling the peritubular uptake of intact PTH by perfused kidneys reported previously appears to play a main role in PTH metabolism by cultured renal cells.
Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas: possible involvement of alpha-2A adrenergic receptor subtype
Authors: Hirose Hiroshi , Maruyama Hiroshi , Itoh Katsuhiko , Koyama Kazunori , Kido Koichi , Saruta Takao
Published: June 2009

Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10−8 and 10−7 mol/l, respectively (p<0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10−6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10−6 and 10−5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10−5 mol/l showed significant antagonism of 10−7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10−5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.
Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions
Authors: Bucht Elisabet , Eklund Anders , Toss Göran , Lewensohn Rolf , Granberg Barbro , Sjöstedt Ulrika , Eddeland Robert , Tørring Ove
Published: June 2009

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N=22), hypercalcaemia of malignancy with skeletal metastases(1 7), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0±4.7 pmol/l) (mean±sd, N=12) and when the kidney function was impaired (4.0±0.9 pmol/l) (N=15) (silica cartridge extraction), whether the subject was hyperalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1±0.5 pmol/1 (N= 15) after immunoextraction and 0.8±0.2 pmol/l(N= 33) after silica cartridge extraction.
Treatment of juvenile goitre with levothyroxine, iodide or a combination of both: the value of ultrasound grey-scale analysis
Authors: Einenkel D , Bauch KH , Benker G
Published: June 2009

The effects of oral iodide, levothyroxine and of iodide and levothyroxine in combination were studied in three groups of 30 children, age 13–15 years, with euthyroid goitre. As endpoints of this study, we used thyroid volume reduction, thyroid hormones, thyrotropin and thyroid grey-scale histograms by computerized analysis. The three groups were well matched with respect to mean age, body weight and pretreatment thyroid volumes and thyroid hormones. Mean urinary iodide excretion before treatment was in the range of 30 μg/g creatinine, since the study was conducted in an iodine-deficient area. All three treatment regimens led to significant reductions in thyroid volume within one month. After six months on 100 μg of levothyroxine, thyroid volume had decreased from 14.1±4.2 ml to 8.3±2.6 2.6ml (mean±sd);on 150 μg of iodide, from 18.5±6.2 ml to 8.8±2.7 ml; and on 100 μg of iodide plus 50μg of levothyroxine, from 17.2±3.1 ml to 8.3±2.0 ml. When treatment was discontinued for three months, or the dosage reduced, thyroid volume increased again in the levothyroxine (to 11.3±2.5 ml) but not in the iodide group. Grey-scale values (by ultrasound, computer-aided estimation) after nine months were significantly different between the three treatment groups; no change was observed with levothyroxine, but after 150 μg of iodide as well as after combined treatment with levothyroxine and iodide there were marked decreases of grey-scale values; this is interpreted as reflecting a decrease in follicle size and colloid content of the thyroid which takes place after iodide supplementation. In conclusion, iodide treatment as well as combined treatment with levothyroxine and iodide lead to volume reduction of juvenile goitre which is quantitatively similar but qualitatively superior compared to the effects of levothyroxine alone.
Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon
Authors: Brixen Kim , Nielsen Henning K , Bouillon Roger , Flyvbjerg Allan , Mosekilde Leif
Published: June 2009

We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p<0.001) and vitamin D-binding protein (p<0.001) increased steadily during treatment returning to baseline at day 14. Total calcitriol (p<0.01) and free calcitriol index (p<0.001) increased transiently at day 4. Furthermore, serum insulin (p<0.001) and both total (p<0.001) and free triiodothyronine (p<0.02) increased during treatment, while serum PTH and plasma glucagon remained unchanged. In conclusion, pharmacological doses of r-hGH increased not only IGF-1 but also free-calcitriol index, insulin, and free T3. The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis.
Growth hormone stimulates galactopoiesis in healthy lactating women
Authors: Milsom Stella R , Breier Bernhard H , Gallaher Brian W , Cox Vanessa A , Gunn Alistair J , Gluckman Peter D
Published: June 2009

Sixteen normally lactating women underwent a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) to assess the effect of hGH on milk production in early lactation. Milk volumes were measured by test weighing procedures of the infants and removal of residual milk on a control day and after 7 days of treatment with recombinant hGH (0.1 IU·kg−1 body weight·d−1) or placebo treatment. Although all women were lactating normally before the study commenced, milk volume in 8 hGH treated mothers was increased (p<0.02) by 18.5±1.4% (mean±sem) compared to 11.6±2.0% in the placebo-treated group (N=8). No adverse effects were seen with hGH treatment and no major changes noted in milk constituents. The hGH concentrations in milk were low and did not change with therapy. Plasma concentrations of IGF-1 increased significantly within 24 h of hGH treatment and increased further towards the end of the trial to values of 2.6-fold above the pretreatment values. The concentration of IGF-1 in milk was approximately 100-fold lower than those observed in plasma and could only be reliably measured after size exclusion chromatography to remove the interfering influence of IGF binding proteins in the radioimmunoassay. All women treated with hGH showed a small increase in milk IGF-1 concentrations but the values remained within the range of values observed in women receiving the placebo treatment (1.2–4.4 μg/l). Growth hormone treatment increased milk volume in normal lactating women during early lactation. This galactopoietic effect of hGH treatment was accompanied by an increase in plasma IGF-1 with no major change in milk constituents and no side effects to the mothers and the babies. Since our results show that a moderate dose of hGH can increase milk volume in healthy, normally lactating women during peak lactation, we suggest that hGH therapy should be considered in future trials for treatment of lactational insufficiency or lactational failure.
Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature
Authors: Laron Zvi , Suikkari Anne-Maria , Klinger Beatrice , Silbergeld Aviva , Pertzelan Athalia , Seppälä Markku , Koivisto Veikko A
Published: June 2009

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p<0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N= 10) or subcutaneous (N=9) administration ofIGF-I (75 μg·kg−1 and 150 μg·kg−1, respectively) in LTD children resulted in a rapid 50–60% fall in serum insulin (p<0.02), a decline in blood glucose and a concomitant 40–60% rise of IGFBP-1 levels (p<0.05). Treatment for seven days with IGF-I (150 μg·kg−1·d−1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p<0.05), in GHD adults by 52% (p<0.02) and in children with constitutional short stature by 17% (p<0.02). IGFBP-1 and insulin concentrations were inversely related in patients with GHD (r= −0.66, p<0.001) or with LTD (r= −0.57, p<0.05). Our data suggest that: (a) increased IGFBP-1 concentration in LTD, GHD and constitutional short children may, at least in part, be accounted for by an IGF-I deficiency; (b) both the rise in IGF-I and a fall in insulin contributed to the rise in IGFBP-1 after acute IGF-I administration; (c) prolonged IGF-I or GH treatment causes a persistent decline in IGFBP-1 concentration. In conclusion, IGF-I and GH may regulate IGFBP-1 secretion either directly or via insulin.
Determination of insulin-like growth factor-2 in feto-maternal circulation during human pregnancy
Authors: Kubota Toshiro , Kamada Shusaku , Taguchi Makoto , Aso Takeshi
Published: June 2009

In order to clarify the roles of insulin-like growth factors (IGFs) on the human maternal-fetal environment, IGF-2 and IGF-1 levels were investigated in human plasma and amniotic fluid during pregnancy. Initially, new radio-immunoassay (RIA) systems for human IGF-2 could be developed. The sensitivity of this assay was 17.5 pg/tube and the cross-reactivity with IGF-1 was 0.64%. The pattern of change of maternal plasma IGF-2 in early pregnancy differed from that of IGF-1, but both IGF levels increased progressively in the second half of gestation, and decreased to non-pregnancy levels in the puerperium. Maternal levels of IGF-2 were approximately seven times greater than those of IGF-1. The ratio of IGF-2 to IGF-1 was 3.2 in amniotic fluid. The IGF concentrations in amniotic fluid obtained in the second trimester were significantly greater than those of term specimens, and closely related to those of prolactin (PRL) in amniotic fluid. The highest IGF-2 to IGF-1 ratio (1 5.9) was found in umbilical vein plasma. On Sephadex G-150 gel-chromatography of maternal and fetal plasma at term, two apparent peaks of unsaturated IGF-2 binding protein (BP) could be detected in both 150 and 40 kilo dalton (kD) regions. One main peak of unsaturated IGF-2 BP could be determined in the 40 kD region in the amniotic fluid at term. High concentration of IGF-2 could be detected in feto-maternal circulation during human pregnancy. Moreover, it is strongly suggested that the releasing systems of IGFs in amniotic fluid are different from those in maternal or umbilical circulation.
Spermatic and peripheral venous plasma concentrations of immunoreactive inhibin in prepubertal boys with undescended testis and in pubertal boys with varicocele
Authors: Orlando Claudio , Santoro Salvatore , Calabrò Carlo , Vannelli Gabriella B , Forti Gianni
Published: June 2009

To obtain more information about testicular inhibin secretion in the prepubertal and pubertal human male, we measured the concentrations of immunoreactive inhibin with a heterologous radioimmunoassay in the spermatic and peripheral venous plasma of 5 prepubertal boys with unilateral undescended testis (Group I, PI), 3 prepubertal boys with inguinal hernia (Group II, P1), and 12 pubertal boys with left idiopathic varicocele. The latter subjects were divided, according to the degree of their pubertal development, in early pubertal (Group III, N = 5, P2) and mid-pubertal groups (Group IV, N=7, P3–4). In Group I, the mean (±sd) spermatic venous concentrations of inhibin (289.4±120.4 ml eq/l) were significantly higher than the corresponding mean peripheral venous concentrations (162.6±47.2; p<0.02) suggesting active testicular secretion of inhibin. In Group II, the spermaticperipheral inhibin gradient was not significant. In pubertal boys with idiopathic varicocele, the mean concentrations of spermatic inhibin were 1076.6±532.0 and 1023.4±274.5 in Groups III and IV, respectively. These levels were about five times higher than the corresponding peripheral concentrations (204.8±41.9 and 238.9±38.9; p<0.005 and p<0.001, respectively). When the data of all the boys were considered together the spermatic venous concentrations of inhibin were significantly correlated with those of peripheral venous FSH (r=0.4749, p<0.05). The spermatic venous inhibin concentrations and the spermatic/peripheral inhibin ratios were significantly correlated also with peripheral LH (r=0.5700 and 0.4766, p<0.01 and <0.05 respectively), spermatic testosterone (r = 0.6237 and 0.5893; p<0.05, respectively), and spermatic/peripheral testosterone ratios (r=0.7529 and 0.7313; p<0.01, respectively). Our results suggest: (a) the undescended testis of prepubertal boys secretes small but significant amounts of inhibin; (b) in pubertal boys with idiopathic varicocele the inhibin secretion of the testis of the affected side is more evident; (c) a contribution of Leydig cells to the testicular secretion of inhibin is likely.
Constitutional delay of growth and adolescence. Results of short-term and long-term treatment with GH
Authors: Bierich Jürgen R , Nolte Klaus , Drews Konrad , Brügmann Gerd
Published: June 2009

During recent years numerous reports on the favourable results of short-term trials with GH in patients with constitutional delay of growth and adolescence (CDGA) have been published, but it has been unclear whether such treatment affects final height. In the present study, the results of long-term therapy with GH in replacement doses have been evaluated in 15 patients who were treated with GH for several years (three years on average). At the start of treatment, 10 of the children were prepubertal and 5 were in puberty. All patients were followed up until final height was reached. Mean final height of the 13 male patients was 170.0±4.4 cm, i.e. −1.58 sds. In the two female patients, final height was 150.0 cm (−3.5 sds) and 164.0cm (−0.8 sds), respectively. Adult height of the patients lagged behind target height by 5.4±3.2 cm (mean±sd), Measured adult height corresponded to adult height as predicted prior to treatment. In conclusion, GH treatment of patients with CDGA did not increase final height.
In vitro synthesis of glycosaminoglycans in endocrine ophthalmopathy
Authors: Kahaly G , Stover C , Beyer J , Otto E
Published: June 2009

The effects of humoral and cell-mediated immunity on the glycosaminoglycan synthesis of retrobulbar fibroblasts was evaluated in patients with endocrine ophthalmopathy. After incubation with IgG and sera, secreted glycosaminoglycans, radiolabeled with D-6-3H-glucosamine and 35sulfate, were precipitated with cetylpyridinium chloride and ethanol. Hyaluronic acid synthesis of human retrobulbar fibroblasts after incubation with sera and IgG and after co-culture with lymphocytes was assessed by means of a radiometric test. Patients' IgG, compared to controls', accounted for a higher secretory stimulation of porcine retrobulbar fibroblasts (as measured by cetylpyridinium chloride precipitation) after 24 and 48 h. Contrasting with 24 h incubation time, glycosaminoglycan values after 48 h were increased two to threefold. Patients' and controls' sera caused earlier and stronger, yet indistinguishable glycosaminoglycan production. Non-sulfated hyaluronic acid was the preponderant glycosaminoglycan secreted into the media by retrobulbar fibroblasts. As assessed with the radiometric test, incubation with patients' and controls' sera and IgG did not reveal a significant difference in stimulating the hyaluronic synthesis of patients' and controls' retrobulbar fibroblasts. When measuring the hyaluronic acid synthesis of controls' and patients' retrobulbar fibroblasts after co-cultivation of lymphocytes, however, patients' lymphocytes had a marked ability to increase the hyaluronic acid concentration compared to controls' lymphocytes. The hyaluronic acid concentration after incubation of a patient's retrobulbar fibroblasts with autologous lymphocytes was markedly more elevated than the intrinsic hyaluronic acid production of retrobulbar fibroblasts. In conclusion, though a significant in vitro influence of patients' IgG and sera on the glycosaminoglycan release of both porcine and human (patients' as well as controls') retrobulbar fibroblasts could not be observed in this study, the indications of a marked stimulatory influence of lymphocytes on the hyaluronic acid secretion of retrobulbar fibroblasts demand further investigation.
Adrenal hormones in human follicular fluid
Authors: Jimena Pilar , Castilla Jose A , Peran Fernando , Ramirez Juan P , Vergara Francisco , Molina Ramon , Vergara Francisco , Herruzo Alfonso
Published: June 2009

Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1±1.1 vs 5.8±2.0 μmol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0±75.9 vs 339.2±37.0 nmol/l; p<0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.