bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of steroid hormones on 5α-reductase activity in female and male genital skin fibroblasts in culture
Authors: Beckmann MW , Wieacker P , Dereser MM , Flecken U , Breckwoldt M
Published: June 2009

The physiological regulation of 5α-reductase (5αR) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5αR activity in female and male genital skin fibroblasts in primary culture to test whether the 5αR activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5αR activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5αR activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5αR activity. (b) In female genital skin fibroblasts, pre-incubation with testosterone also led to an increase in 5αR activity, whereas pre-incubation with estradiol decreased 5αR activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5αR activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens. Furthermore, the data suggest that the 5αR activity regulation of genital skin fibroblasts is different in female and male.
The expression of insulin-like growth factors and their binding proteins in normal human lymphocytes
Authors: Nyman Tuulikki , Pekonen Fredrika
Published: June 2009

The expression of insulin-like growth factors and their binding proteins in normal human peripheral lymphocytes was studied using the reverse transcriptase polymerase chain reaction method and Western ligand blotting. A quantitation of RT-PCR products was used to study the differences between normal and PHA stimulated lymphocytes. Normal freshly collected lymphocytes expressed mRNAs for both IGF-I receptor and IGF-II receptor but no expression of the corresponding growth factors was detectable. After stimulation with phytohemagglutinin the lymphocytes, however, expressed both IGF-I and IGF-II. Of the five IGFBPs examined, unstimulated lymphocytes expressed only IGFBP-2 and -3. Stimulated lymphocytes expressed IGFBP-4 and -5, in addition to IGFBP-2 and -3, whereas IGFBP-1 mRNA remained undetectable. The ligand blotting of lymphocyte conditioned media revealed production of 34K. 43K and 49K IGFBPs. The addition of estrogen, progesterone, IGF-I or growth hormone did not affect secretion of IGFBPs by lymphocytes.
An ACTH-secreting bronchial carcinoid: presence of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in the tumor tissue
Authors: Murakami Osamu , Takahashi Kazuhiro , Sone Masahiko , Totsune Kazuhito , Ohneda Makoto , Itoi Keiichi , Yoshinaga Kaoru , Mouri Toraichi
Published: June 2009

The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 μg. iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropinreleasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.
Is there a place for urinary growth hormone measurement?
Authors: Moreira-Andrés Maria N , Cañizo Francisco J , Hawkins Federico
Published: June 2009

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.
Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance
Authors: Lanng Susanne , Thorsteinsson Birger , Røder Michael E , Ørskov Cathrine , Holst Jens J , Nerup Jørn , Koch Christian
Published: June 2009

Pancreatic and gut hormone responses to oral glucose, and insulin sensitivity were studied in cystic fibrosis patients with normal (N= 14), impaired (N=4), and diabetic (N= 12) glucose tolerance, and in 10 control subjects, and beta cell responses to oral glucose and intravenous glucagon were compared. Compared to control subjects, initial insulin and C-peptide responses to oral glucose were lower in all patient groups, and decreased with decreasing glucose tolerance. Insulin sensitivity in patients with impaired and diabetic glucose tolerance was lower than in control subjects. The 6 min post-glucagon C-peptide concentration was positively correlated with the initial insulin response to oral glucose. Fasting levels of pancreatic polypeptide, pancreatic glucagon, total glucagon, glucagon-like peptide-1 7-36 amide, and gastric inhibitory polypeptide were normal in all patient groups. Following oral glucose, pancreatic polypeptide responses were absent in all patients, suppressibility of pancreatic glucagon secretion was increasingly impaired with decreasing glucose tolerance, and gut hormone levels were normal. In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact.
Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction?
Authors: Rasmussen Michael Højby , Carstensen Helle , List Søren , Schwartz Thue W , Hilsted Jannik
Published: June 2009

The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 1 5 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion in insulin-dependent diabetic patients. Alternatively, the reduction in PP secretion in these patients reflects dysfunction of the PP secreting cells of the pancreas. Iv injection of cholecystokinin-8 elicited a small but significant increase in PP concentrations, while iv secretin did not increase PP concentrations at all in healthy subjects. These stimuli are therefore less suitable in the assessment of vagal neuropathy.
Mortality in patients treated for hyperthyroidism with iodine-131
Authors: Hall Per , Lundell Göran , Holm Lars-Erik
Published: June 2009

Causes of death were studied in 10,552 Swedish hyperthyroid patients treated with 131I diagnosed between 1950 and 1975. The patients were followed for an average of 15 years (range 0-35 years) and were matched with the Swedish Cause of Death Register. A total of 5,400 deaths were observed and the overall standardized mortality ratio was 1.47 (95% confidence interval (CI) 1.43-1.51). The standardized mortality ratio for females was 1.50(95% CI 1.46-1.55) compared to 1.31(95% CI 123-1.39) in males. The most common cause of death (61%) was from cardiovascular diseases (standardized mortality ratio 1.65; 95% CI 1.59-1.71). Significantly elevated risks were also seen for tumours, diseases of the endocrine system, respiratory system, gastro-intestinal system, and congenital malformations. In all causes of death, except tumours and trauma, decreasing standardized mortality ratios over time were seen. Patients followed for more than 10 years had significantly elevated risks for tumours, diseases of the endocrine, respiratory, and cardiovascular systems. Patients given higher 131I activity and younger patients had higher standardized mortality ratios than those given lower activity and older patients. The hyperthyroidism per se. rather than the 131I treatment, appeared to be the major explanation for the elevated mortality.
Heterogeneity of neuropeptide Y immunoreactivity in patients with pheochromocytoma: influence on the diagnostic power of measuring plasma NPY using antisera with different specificities
Authors: Tabarin Antoine , Cassiède Pierre , Minot Anne Perrot , Cuber Jean Claude , Roger Patrick , Ducassou Dominique
Published: June 2009

The nature of NPY-like immunoreactivity (NPY-LI) was investigated in plasma and tumour tissue of 1 7 pheochromocytoma patients by HPLC, gel filtration and isoelectric focusing using two radioimmunoassays (RIAs) directed against the C- and N-terminals of NPY respectively. The two RIAs gave similar results in pheochromocytomas: 86% of cases had higher NPY-LI concentrations than those found in normal adrenal glands and NPY-LI behaved like authentic human NPY during gel filtration and HPLC. Assessed by isoelectric focusing, NPY was found to be amidated in seven of nine tumours. Contrary to the findings obtained in tumours, the results of the two RIAs in plasma samples were not always concordant: compared to controls, elevated concentrations of NPY-LI were found in 86% of cases of pheochromocytomas using the C-terminally directed RIA and in 76% of cases using the N-terminally directed RIA. The results of HPLC and gel filtration of NPY-LI in plasma suggested that circulating Cand N-terminal NPY fragments account for the discrepancy between the results of the two RIAs. In conclusion, most pheochromocytomas contain large amounts of NPY-LI that behaved like authentic NPY by chromatographic analysis. On the contrary, circulating NPY-LI in some pheochromocytoma patients is heterogeneous with cleaved products which influence differently the power of the C- and N-terminally directed RIAs for the diagnosis of pheochromocytoma.
Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients
Authors: Andersen Per H , Richelsen Bjørn , Bak Jens , Schmitz Ole , Sørensen Niels S , Lavielle Rodolphe , Pedersen Oluf
Published: June 2009

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1±3.2, placebo vs 103.3±3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2±0.2 vs 5.7±0.2 mmol/l, p<0.01), serum insulin (168.0±14.5 vs 138.9±7.9 pmol/l, p<0.05), serum C-peptide (0.68±0.03 vs 0.58±0.02 nmol/l, p<0.05) and total serum cholesterol (6.07±0.41 vs 5.48±0.38 mmol/l, p< 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p<0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p<0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU·kg−1·min−1) glucose disposal rate tended to be increased (18%, p=0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.
Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women
Authors: Rymer Janice , Crook David , Sidhu Mandeep , Chapman Michael , Stevenson John C
Published: June 2009

Objective:

To evaluate the effects of tibolone (Org OD14), a synthetic steroid used for the relief of postmenopausal symptoms, on serum concentrations of lipoprotein(a) (Lp(a)), an independent risk marker for coronary heart disease. Design: Subset of women participating in a non-randomized prospective trial of tibolone therapy. Twenty-seven women requesting relief of menopausal symptoms were treated with tibolone 2.5 mg/day for six months; 27 women who did not request treatment acted as controls. Results: Tibolone induced a substantial fall (p<0.001) in serum Lp(a) levels (median change −48%, range −100% to +3%). Conclusions: In terms of cardiovascular risk, the ability of tibolone to lower serum concentrations of Lp(a) may be advantageous in view of the unwanted reduction in high density lipoprotein concentrations which has previously been demonstrated in users of this steroid.
The effect of single doses of inhaled beclomethasone dipropionate on the circadian rhythm in serum osteocalcin in normals
Authors: Nielsen Henning K , Pedersen Bente , Brixen Kim , Dahl Ronald , Charles Peder
Published: June 2009

A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 μg and 1000 μg beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 2 3-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 1 7.00 the following day; 1000 μg beclomethasone, but not 250 μg, suppressed serum cortisol by 14.4±6.7% (p=0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin.
In vivo acute testicular testosterone response to injection of luteinizing hormone in the rat fetus
Authors: Habert René
Published: June 2009

The acute in vivo testosterone response to LH stimulation and its change during late fetal life were determined in the rat. In 18.5-day-old fetuses, testicular testosterone content was increased in a dose-and time-dependent manner after fetal subcutaneous LH injection. The maximum response was small: the testicular content and plasma concentration were increased by 200% and 2 50% over basal values respectively, while they were increased 1100% and 1200% in adult rats. Similarly, comparable low responses were obtained after subcutaneously injecting the fetuses with human chorionic gonadotropin (hCG) and after injecting LH into the vitelline vein. Between days 18.5 and 21.5 of fetal life, the testosterone levels in the testis and plasma of uninjected or PBS-injected fetuses decreased and were comparable in both groups. In maximally LH-stimulated fetuses, the testicular content did not change with age, and plasma concentration was lower on day 21.5 than on day 18.5. Since the number of Leydig cells increases 1.5 to 2-fold between days 18.5 and 21.5, these results show an age-related decrease in basal and maximally LH-stimulated in vivo testosterone secretions per Leydig cell during late fetal life.
The role of calcium ions in rat Leydig cell steroidogenesis induced by atrial natriuretic peptide
Authors: Foresta Carlo , Mioni Roberto
Published: June 2009

The aim of this study was to clarify whether calcium ions play a role in the mechanisms by which rat atriopeptin II exerts its stimulatory effects on rat Leydig cell steroidogenesis. The absence of calcium in the medium and the calcium channel-blocker drug, verapamil, both significantly inhibited testosterone production in rat atriopeptin Il-treated rat Leydig cells. Similar effects were observed on human chorionic gonadotropin-stimulated Leydig cells. Furthermore, 8-Bromoguanosine 3′: 5′ cyclic mono-phosphate, the putative second messenger of atrial natriuretic peptide, significantly increased rat Leydig cell steroidogenesis, determining a stimulatory effect comparable to that obtained with rat atriopeptin II. Calcium-free medium and verapamil inhibited this stimulatory effect. The addition of a calcium ionophore, A-23187, significantly counteracted the inhibitory effect of verapamil on rat atriopeptin II-induced and 8-Bromoguanosine 3′:5′ monophosphate-induced testosterone production. Furthermore, rat atriopeptin II significantly stimulated the calcium flux through the plasma membrane, as evaluated by the 45Ca2+ uptake method. This effect was strongly inhibited by the addition of verapamil. These data underline that calcium ions may play a role in the mechanisms by which atriopeptin II stimulates rat Leydig steroidogenesis, although other post-receptor systems cannot be excluded.
Life events in the pathogenesis of Graves' disease. A controlled study
Authors: Sonino Nicoletta , Girelli Maria E , Boscaro Marco , Fallo Francesco , Busnardo Benedetto , Fava Giovanni A
Published: June 2009

Contradictory findings have been reported about a possible causal relationship of life stress to Graves' disease. We evaluated this issue by investigating the occurrence of stressful life events in the year before the first signs of disease onset, using methods that have been found to be valid and reliable in psychosomatic research. Seventy consecutive patients with Graves' disease and a control group of 70 healthy subjects, matched for sociodemographic variables, were studied. Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients, not during the acute phase of illness but while on remission, by antithyroid drug treatment. Patients with Graves' disease reported significantly more life events compared to controls (p<0.001). They also had more independent events (p<0.001) and events that had an objective negative impact (p <0.001) according to an independent rater, unaware whether the events had occurred in patients or controls. All categories of events were found to be significantly more frequent in patients suffering from Graves' disease than in controls. By rigorous methods (inclusion of patients with Graves' disease only, careful dating of the onset of symptoms, accurate event definition, delay of the interview upon disease remission, use of a blind rater for judging independence and objective negative impact), our results support the concept of an excess of life events in Graves' disease. Stressful life events may affect the regulatory mechanisms of immune function in a number of ways. Within the extreme complexity of the phenomena implicated in the pathogenesis of autoimmune thyroid hyperfunction, our findings emphasize the role of emotional stress.
The effects of propranolol and verapamil on hyperthyroid heart symptoms and function, assessed by systolic time intervals
Authors: Nordin Henrik , Galløe Anders M , Ladefoged Søren D , Badskjær Jørn
Published: June 2009

The effects of acute and chronic administration of propranolol and verapamil on heart rate and systolic time intervals were studied in 10 hyperthyroid patients and 10 normal subjects, both groups without signs of cardiovascular or pulmonary disease. In normal subjects iv propranolol reduced heart rate significantly, and both drugs increased the total electromechanical systole significantly without difference between the drugs. This effect was insignificant when the drugs were given orally. In hyperthyroid patients both drugs reduced heart rate significantly in acute and chronic administration, and no difference between the two drugs was found. Neither drug altered cardiac contractility as assessed by systolic time intervals. These results indicate that the metabolic effects of thyroid hormone on contractility were unaltered and unblocked by the drugs. None of the participants developed signs of heart failure. Verapamil can thus be used as an alternative to propranolol in the treatment of tachycardia in hyperthyroidism.
Different responses in little and bigbig prolactin to metoclopramide in subjects with hyperprolactinemia due to 150–170 kD (bigbig) prolactin
Authors: Bjøro T , Johansen E , Frey HH , Turter A , Torjesen PA
Published: June 2009

We have studied in vivo induction of serum prolactin (PRL) levels in four females and one male, and regulation of PRL in the menstrual cycle in three females all with hyperprolactinemia with large amounts (72–92%) of bigbig PRL (MW 150–170 kD). Metoclopramide (MTC) iv induced a 4–29-fold increase in little PRL (25 kD PRL) at 30 min, while the increase in 150–170 kD PRL was 1.1–2.2-fold. The maximal response in 150–170 kD PRL was seen after 2–6 h, and the decrease after the maximal PRL values for 150–170 kD PRL was delayed compared to the decrease in 25 kD PRL. The different kinetics for 25 kD PRL and 150–170 kD PRL was responsible for the prolonged increase in total PRL seen in the subjects with large amounts of 150–170 kD PRL compared to the controls. The percentage of 1 50–170 kD PRL decreased to 29–60% at 30 min and returned to unstimulated values after 6–24 h. In contrast, prolonged stimulation of PRL secretion, as in the luteal phase, did not change the percentage of 150–170 kD PRL. In a male subject secreting large amounts of 1 50–170 kD PRL the increase in PRL after MTC was less, while the temporal changes in the 25 kD PRL levels were almost the same as in the females.
Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes
Authors: Deyssig Roman , Frisch Herwig , Blum Werner F , Waldhör Thomas
Published: June 2009

The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4±0.5 years; ideal body weight 122±3.1%, body fat 10.1±1.0%; mean±sem) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)−1 day−1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding protein, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency. In highly trained power athletes with low fat mass there were no effects of GH treatment on strength and body composition.
The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females
Authors: Pijl Hanno , Koppeschaar Hans PF , Willekens Frans LA , Frölich Marijke , Meinders A Edo
Published: June 2009

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI)35.6±1.0 kg/m2) and nine women of normal weight (BMI 22.9±0.9 kg/m2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal concentrations of pituitary hormones were measured at 09.00. Subsequently 200 μg of TRH and 100 μg of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, β-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses. These results suggest that impaired serotonergic neurotransmission plays a role in the lower basal PRL concentrations in obese subjects. They do not provide evidence that a serotonergic defect influences the releasing hormone-induced pituitary hormone release in obesity. Furthermore, the findings indicate that serotonergic neurotransmission inhibits TSH release in response to TRH in both obese and normal subjects.
Opposite effects of growth hormone and estrogens on the pregnancy zone protein serum levels in children and adolescents
Authors: Devriendt K , Massa G , de Zegher F , Vanderschueren-Lodeweyckx M , Cassiman JJ , Van den Berghe H , Marynen P
Published: June 2009

Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 μg/l vs 434 μg/l; p≤0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng·kg−1·d −1 ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone.
Plasma corticotropin-releasing hormone, β-endorphin and cortisol inter-relationships during human pregnancy
Authors: Chan Eng-Cheng , Smith Roger , Lewin Terry , Brinsmead Max W , Zhang Hong-Ping , Cubis Jeff , Thornton Kathryn , Hurt Di
Published: June 2009

To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), β-endorphin (βEP), cortisol and obstetric events during pregnancy, blood samples were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, βEP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and βEP were correlated (r=0.30, p<0.001). (3) During labour, no correlations were found among maternal plasma CRH, βEP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p<0.05) as were maternal and fetal βEP (r=0.43, p<0.001). (7) Fetal obstetric difficulty was correlated with fetal βEP (r=0.54, p<0.001). Our findings support the hypothesis that maternal plasma CRH regulates maternal βEP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress.
Single nucleotide substitution of the androgen receptor gene in a case with receptor-positive androgen insensitivity syndrome (complete form)
Authors: Kasumi Hiroyuki , Komori Shinji , Yamasaki Noriyuki , Shima Hiroki , Isojima Shinzo
Published: June 2009

Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H] dihydrotestosterone(17β-hydroxy-5α-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotesterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine→cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine→alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.
Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium
Authors: Aanestad Marie , Røtnes J Sigurd , Torjesen Peter A , Haug Egil , Sand Olav , Bjøro Trine
Published: June 2009

Epidermal growth factor (EGF) stimulated the prolactin (PRL) synthesis and release from the GH4C1 cells in a dose-dependent manner. The ED50 was between 10−11 and 10−10 mol/l. The maximal effect was obtained at 10−9 mol/l EGF for the release, and 10−8 mol/l EGF for the synthesis. EGF stimulated the release of PRL from cell perfusion columns after a lag period of about 30 s. The maximal secretion of PRL occurred about 60 s after the start of stimulation. The PRL secretion declined to basal levels within 2 min. The EGF-stimulated PRL release was additive to the secretion evoked by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). An instantaneous increase in the intracellular concentration of free calcium, [Ca2+]i, of the GH4C1 cells was observed after the administration of EGF. EGF modified neither the basal nor the TRH-stimulated inositoltrisphosphate production in the GH4C1 cells, and EGF did not show any effect on the cyclic adenosine monophosphate production of these cells.
Homologous desensitization of calcitonin receptors and calcitonin-dependent adenylate cyclase in T47D cells
Authors: Schneider H-G , Raue F , Koppold A , Ruf W , Ziegler R
Published: June 2009

Prolonged use of calcitonin (CT) in vivo leads to a loss of biological response (escape). To understand the molecular basis of this phenomenon, we examined desensitization of calcitonin receptors and down-regulation of adenylate cyclase response to CT in T47CD cells after a preincubation with CT. Preincubation with salmon or human CT (sCT, hCT) for 3 h led to a concentration-dependent loss of [125I]-sCT binding and a similar loss of adenylate cyclase response to a maximal stimulatory dose of sCT. At the same time there was an increased basal activity of the adenylate cyclase. After 24 h preincubation with sCT, basal cAMP levels fell considerably but not to basal levels. Time course experiments showed a delayed decline of maximally sCT-stimulated cAMP levels, which started after 1 h, while binding values declined over the first 60 min to one-third of the original values. Upon removal of CT from the medium, recovery of hormone binding occurred in parallel with the recovery of the adenylate cyclase response to sCT. T47D cells incubated with 25 μmol/l monensin, a lysosomal inhibitor, showed a persistent [125I]-sCT binding after removal of hormone, consistent with diminished intracellular receptor degradation. However, despite persistent binding to the cells, basal and stimulated cAMP levels dropped in the same manner as seen in controls. Our experiments support the view that tight binding of CT to its receptor stimulates adenylate cyclase in T47D cells, until receptors are removed by internalization. The physiological role of internalization of the CT receptor might be to end continuous stimulation of the adenylate cyclase, which occurs after binding.
CV 205-502 in acromegaly
Authors: Chiodini Pier Giorgio , Attanasio Roberto , Cozzi Renato , Dallabonzana Daniela , Oppizzi Giuseppe , Orlandi Paola , Strada Sonia , Liuzzi Antonio
Published: June 2009

In a series of acromegalic patients the effects of CV 205-502, a new long-acting dopamine-agonist drug, on growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were evaluated in an open study. After acute administration of CV 205-502 (0.0375 mg, po) in 12 patients, GH levels did not change, whereas PRL values significantly decreased and remained suppressed for 24 h. In the 14 patients who underwent chronic CV 205-502 treatment (at daily doses of 0.1 50-0.600 mg/day given at bedtime or b.i.d. for up to 12 months), GH and IGF-I levels fell significantly from 60±17(mean±sem) μg/l to 28±10 μg/l and from 1127±84 μg/l to 738±57 μg/l. respectively (p<0.05). A retrospective comparison with the results obtained for the same patients during a previous chronic bromocriptine treatment (at daily doses of 5–20 mg given t.i.d. or q.i.d.) did not show any significant difference in the suppression of GH levels between the two treatments; no bromocriptine-resistant patient was CV 205502 sensitive, even at the highest CV 205-502 dose used. We conclude that in acromegaly chronic treatment with this new dopaminergic drug has a GH- and PRL-lowering effect that is similar to but more prolonged than that of bromocriptine, and normal or near-normal GH and IGF-I levels may be obtained in a few patients with b.i.d. administration. However, no GH-lowering effect is observed in bromocriptine-resistant patients.
Growth hormone therapy in achondroplasia
Authors: Nishi Yoshikazu , Kajiyama Michi , Miyagawa Shinichiro , Fujiwara Mitsuhiro , Hamamoto Kazuko
Published: June 2009

The status of growth hormone (GH) secretion together with the effect of GH therapy was studied in six children with achondroplasia. One patient had impaired GH secretion, which may, in part, be due to obesity. The pre-GH-treatment height velocity was 3.8±0.7 cm/year, but this increased to 6.0±1.0 cm/year in the first year of treatment and to 4.4±0.6 cm/year in the second year. One patient who underwent GH therapy for 4 years showed good response in height velocity. A considerable variation was observed in response to GH therapy within the treated cases.
Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells
Authors: Jones TH , Kennedy RL , Justice SK , Price A
Published: June 2009

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-γ and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.
Detection of growth hormone, prolactin and human β-chorionic gonadotropin mRNA in growth hormone-secreting pituitary adenomas and in prolactin-secreting pituitary adenomas by in situ hybridization using a non-isotopic detection method
Authors: Tallen Gesche , Fehr Susanne , Saeger Wolfgang , Uhlig Holger , Lüdecke Dieter K
Published: June 2009

A non-isotopic in situ hybridization method with digoxigenin-labelled probes was used to examine growth hormone (GH), prolactin (PRL) and human β-chorionic gonadotropin (β-hCG(LH)) gene expression in 63 pituitary tumours in acromegaly and 20 adenomas in hyperprolactinaemia. hCG and LH were detected simultaneously because of the extensive homology (more than 90%) of their mRNA sequences (1). A comparison with former results obtained with 35S-labelled probes shows the value of the easier and faster non-isotopic method. Additionally, immunohistochemical data are included to give even more evidence for the synthesis of the respective hormones by the tumour cells. In all 63 adenomas in acromegaly, GH mRNA was revealed in 59 PRL mRNA and in 36 β-hCG(LH) mRNA. A positive immunostaining for GH was found in all, for PRL in 40, and for β-hCG(LH) in 34 adenomas. The comparison of the two in situ hybridization methods revealed no differences concerning GH mRNA detection, but not all tumours positive after non-isotopic PRL and β-hCG(LH) mRNA detection showed signals with the radioactive method. Referring to the 20 PRL-secreting adenomas, PRL gene expression was demonstrable in all, GH mRNA in 12, and β-hCG(LH) mRNA in 2 cases. Comparing the positive results of immunohistochemistry with those of in situ hybridization, correspondence was found in 19 cases for PRL, in 5 cases for GH and in no case for β-hCG(LH).
Skeletal muscle sodium and potassium changes after successful surgery in acromegaly: relation to body composition, blood glucose, plasma insulin and blood pressure
Authors: Landin Kerstin , Petruson Björn , Jakobsson Karl-Erik , Bengtsson Bengt-Åke
Published: June 2009

The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p <0.01) but the sodium content and the Na/K ratio were lower (p<0.05 and p<0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [median (range)] 9.8 (9.2–11.5) to 7.7 (5.7–9.5) mmol/100 g wet wt (p<0.001). The skeletal muscle sodium content increased from 2.8 (2.5–3.9) to 5.1 (4.3–6.7) mmol/100 g wet wt (p<0.001) and the Na/K ratio increased from 0.28 (0.26–0.38) to 0.56 (0.51–1.18) (p< 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39–0.84) (p<0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.
Plasma calcitonin, IGF-I levels and vertebral bone mineral density in hyperprolactinemic women during bromocriptine treatment
Authors: Tørring Ove , Isberg Bengt , Sjöberg Hans Erik , Bucht Elisabet , Hulting Anna Lena
Published: June 2009

Hyperprolactinemia is associated with decreased bone mineral density, which may be caused by the hypogonadism and hypoestrogenicity noticed in patients with hyperprolactinemia. Since calcitonin inhibits the bone resorption, and insulin-like growth factor I (IGF-I) has important anabolic effects on the skeleton, lack of one or both peptides may contribute to the development of osteopenia. We therefore measured the plasma calcitonin and IGF-I levels in nine women with hyperprolactinemia caused by a prolactin-producing pituitary tumor. The calcium-stimulated C-cell reactivity was studied by measuring calcitonin in plasma during a calcium clamp before and after normalization of serum prolactin during treatment with bromocriptine. Basal CT levels were measurable but lower than in healthy controls. Basal IGF-I levels and calcium-stimulated plasma calcitonin were normal in the hyperprolactinemic state and similar to the calcitonin and IGF-I levels during bromocriptine treatment. The serum prolactin levels decreased (p<0·001) and the serum estradiol levels increased (p<0·001). The bone mineral density of the lumbar spine increased significantly during treatment. Thus, basal plasma CT levels are slightly reduced in hyperprolactinemic women. However, the reversible osteopenia in hyperprolactinemic women is less likely to be caused by inhibited IGF-I secretion or by deficient CT levels since the CT response to calcium is normal. In addition, bromocriptine treatment with normalization of prolactin levels is beneficial for the bone mineral content in this condition.
Immunoreactive inhibin in human follicular fluid in an ovarian hyperstimulation programme for in vitro fertilization: correlations and different forms
Authors: Reichardt Bärbel , Mehltretter Gerhard , Lechner Karin , Rjosk Hans K , Müller Otto A , Schopohl Jochen
Published: June 2009

The inhibin concentration in 131 samples of human follicular fluid obtained from 31 women undergoing ovarian hyperstimulation for in vitro fertilization was measured using specific double antibody radioimmunoassay. We used the synthetic 1-32-α-inhibin as standard and radioiodinated 1-32-Tyr-α-inhibin as tracer. Antibodies were raised in rabbits by immunization with the synthetic peptide. Estradiol and progesterone concentrations were measured using commercial radioimmunoassays. Results: The inhibin concentration correlated with the estradiol (r = 0.57, N = 88.p<0.0001) and progesterone (r=0.82, N=88. p<0.0001) concentrations in human follicular fluid. The dosage of human menopausal gonadotropin given to individual patients correlated with the average inhibin concentration measured in their follicles (r = 0.72, N = 23, p<0.0001). Similarly, the size of follicles correlated with their inhibin content (r = 0.75, N = 131, p<0.0001). Nineteen samples of human follicular fluid originating from follicles of different size and volume were examined using gel-chromatography. In each human follicular fluid the main form of inhibin (32 kDa) was recovered. In small follicles (3 ml) we found 12.8±9.1% (mean±sd) of the whole immunoreactive inhibin eluating in the area of V0 (≤80 kDa). In the larger follicles (4-7 ml), however, only 4.4±4.2% of this large inhibin form could be found. Conclusions: Our data confirm that human menopausal gonadotropin stimulates ovarian inhibin production. In addition to the estradiol and progesterone concentrations, the inhibin concentration may be an index of granulosa cell function and follicular maturation. The occurrence of large molecular weight forms of inhibin in small follicles remains unclear. They may represent large precursor molecules which are proteolytically cleaved in more mature follicles.