bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum inhibin during lactation: relation to the gonadotrophins and gonadal steroids
Authors: Burger H. G. , Hee J. P. C. , Mamers P. , Bangah M. , Zissimos M. , McCloud P. I. 
Published: March 2008

SummaryOBJECTIVE The aims of the study were to describe the changes in serum immunoreactive inhibin (INH) during normal lactation and to examine the relations between INH, oestradiol (E2) and follicle stimulating hormone (FSH), particularly during the first weeks post partum.DESIGN Blood samples were obtained from normally lactating women for hormone measurements at dally intervals until discharge from hospital, and subsequently at weekly intervals until the resumption of menses, or one year post partum.SUBJECTS Eighteen breast feeding women aged 27–36 years volunteered for the study.MEASUREMENTS INH, FSH, luteinizing hormone (LH), prolactin (PRL), E2, and progesterone (P4) were measured by standard radioimmunoassays. Non‐linear modelling was used to quantify the hormone patterns observed.RESULTS Hormone levels were compared with those found in the follicular phase of the normal menstrual cycle. Levels of INH fell rapidly in the first week post partum and remained at the lower end of the follicular phase range for the period of study, rising only just prior to resumption of menses. E2 fell more slowly, into the follicular phase range, reaching the lower end of that range only at about approximately 100 days post partum. FSH levels were suppressed initially below the follicular phase range, commencing to rise 4·7‐24 days post partum, reaching a plateau high in the follicular phase range 17·5–53 days post partum, and subsequently showing a slow decline. Human chorionic gonadotrophin (hCG), initially measured because of its cross‐reactivity in the LH assay, fell rapidly post partum and LH remained in the low follicular phase range for several weeks. PRL fell slowly throughout and was still elevated at 150 days post partum, while P4 fell very rapidly and was less than 1 nmol/l until just prior to first menses.CONCLUSIONS inhibin levels fall rapidly post partum and remain low until close to the time of resumption of follicular activity and menses. The post partum rise in serum FSH appears to be much more closely related to falling oestradiol levels than to the very early and rapid fall in inhibin. Oestradiol thus appears to be the predominant negative feedback factor influencing FSH secretion during the post partum period. The low inhibin levels may allow FSH to rise to levels high in the follicular phase range under the predominant negative feedback control of oestradiol. Inhibin levels do not appear to be a suitable marker of returning fertility.
Testosterone administration increases adrenal response to adrenocorticotrophin
Authors: Polderman Kees H. , Gooren Louis J. G. , van der Veen Eduard A. 
Published: March 2008

OBJECTIVES Various studies have demonstrated coexistence of ovarian and adrenal hyperandrogenism in women. This study was designed to determine whether testosterone can increase the response of the adrenal gland to stimulation by adrenocorticotrophin (ACTH).DESIGN Non‐randomized intervention in a university teaching hospital.PATIENTS Twenty androgen‐treated female‐to‐male transsexual patients (10 ovariectomized and 10 non‐ovariectomized) and 10 normal female controls.MEASUREMENTS ACTH stimulation tests were performed in all subjects. Baseline values and the increase above baseline values after ACTH stimulation were assessed for cortisol and the adrenal androgens androstenedione, dehydroepiandrosterone and dehydroepiandrosterone‐sulphate.RESULTS Increases in levels of cortisol, androstenedione and dehydroepiandrosterone after administration of ACTH were greater in testosterone‐treated transsexual patients than controls.CONCLUSION We conclude that testosterone increases the response of the adrenal gland to stimulation by ACTH.
Acute cholinergic blockade with low dose pirenzepine reduces the insulin and glucose responses to a mixed meal in obese women with the polycystic ovary syndrome
Authors: Premawardhana L. D. K. E. , Ismail I. S. , Riad‐Fahmy D. , Miell J. P. , Peters J. R. , Scanlon M. F. 
Published: March 2008

OBJECTIVES Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal in a dose dependent fashion in normals and in patients with non‐insulin dependent diabetes. We have studied the effects of pirenzepine on plasma insulin, plasma glucose, growth hormone (GH), androstenedione, testosterone, insulin‐like growth factor‐I (IGF‐I) and IGF binding protein 1 (IGFBP‐1) responses to a mixed meal in obese clinically hyperandrogenic women with the polycystic ovary syndrome.SUBJECTS AND METHODS Six obese women with polycystic ovary syndrome (BMI range 27·3–39·8 kg/m2) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours.RESULTS Mean fasting plasma insulin concentrations were increased. Peak post‐prandial plasma insulin concentrations were reduced significantly by all three doses used. Post‐prandial integrated plasma insulin concentrations were reduced by the two higher doses. Peak postprandial plasma glucose concentrations were also reduced. The late post‐prandial GH surge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF‐I and IGFBP‐1 concentrations were not significantly different when placebo was compared with pirenzepine 200 mg.CONCLUSIONS Acute cholinergic muscarinic blockade with pirenzepine significantly reduces meal stimulated plasma insulin and plasma glucose concentrations in clinically hyperandrogenic women with polycystic ovary syndrome. The ability of pirenzepine to reduce plasma insulin without worsening glycaemia is a particular advantage and may be therapeutically relevant. Further studies are under way to assess the usefulness of pirenzepine in long‐term suppression of plasma insulin in this group of patients.
Subnormal growth hormone responses to acutely administered dexamethasone in depression
Authors: Thakore Jogin H. , Dinan Timothy G. 
Published: March 2008

OBJECTIVES Acute oral administration of dexamethasone (DEX) stimulates growth normone (GH) release at 3 hours in normal controls and provides us with a novel probe with which to study the somatotrophic axis. In affective illness GH release is subnormal In response to a number of stimuli. We decided to investigate the acute effects of DEX‐induced GH release in depression.DESIGN A between subjects parallel group design was employed.METHODS Baseline levels of GH and cortisol were taken after which 4 mg of oral DEX was administered. Plasma samples for GH estimation were taken at +60, +180, + 240 and + 300 minutes.PATIENTS Sixteen normal subjects and 16 unipolar, non‐psychotic, melancholic DSM‐111R major depressives were studied. Depressed subjects had to score over 17 on the Hamilton Depression Rating Scale; the mean ± SEM scores were 27·4±1·0.MEASUREMENTS Plasma GH and cortisol levels were measured by radioimmunoassay.RESULTS Baseline mean ± SEM GH levels (depressives 2·4 ±0·6 mU/l; controls 2·6 ±0·4 mU/l) did not differ significantly between the two groups (P < 0·28). DEX‐induced GH secretion was subnormal in depressives as opposed to controls (2·1±0·7 vs 19·4±2·2 mU/l, P < 0·001). There were significant differences between the two groups at 60, 180 and 240 minutes (P < 0·05). Baseline cortisol values were significantly different between the two groups (depressives 303·3 ±31·5 nmol/l; controls 138 ± 4·7 nmol/l). An analysis of covariance, with cortisol as a covarlate, still found the depressives to have significantly subnormal GH responses as compared to the control group (P < 0·05).CONCLUSION Dexamethasone‐induced GH release is subnormal in depression.
Measurement of thyroid stimulating immunoglobulins in a new cell line transfected with a functional human TSH receptor (JPO9 cells), compared with an assay using FRTL‐5 cells
Authors: Michelangell V. P. , Munro D. S. , Poon C. W. , Frauman A. G. , Colman P. G. 
Published: March 2008

OBJECTIVES Most bioassays used to measure thyroid stimulating antibodies (TSAb) rely on the ability of patient sera to generate cAMP in cultured cells of non‐human origin. The cell line most commonly used has been the rat thyroid cell line, FRTL‐5. Recently, a new cell line (JPO9) possessing a transfected human TSH receptor has been developed. The aim of this study was to evaluate the JPO9 cells by comparing them with the widely used FRTL‐5 cells, using the method of 3H‐adenine incorporation for the direct measurement of intracellular cAMP.DESIGN The ability of patient sera to generate cAMP production in JPO9 and FRTL‐5 cells was used as the index of thyroid stimulation. The specificity of the assay was determined using sera from patients with autoimmune thyroid and non‐thyroid autoimmune diseases.PATIENTS We studied sera from 28 patients with newly diagnosed Graves' disease, 72 patients with Graves' disease at various stages of treatment, 8 patients with Hashimoto's thyroiditis, 40 patients with a variety of non‐thyroid autoimmune diseases and 42 control subjects.MEASUREMENTS The intracellular 3H‐cAMP generated in JPO9 cells following preincubation with 3H‐adenine and subsequent incubation with patient or control sera, was used as a measure for TSAb. The results obtained with these cells were compared to those obtained with the widely used FRTL‐5 cells and they were also correlated with the measurement of TSH binding inhibitory immunoglobulins by a conventional radioreceptor assay.RESULTS JPO9 cells were more sensitive and had a wider range of response to bovine TSH (bTSH) than had FRTL‐5 cells (10‐7‐10‐2 U/ml compared to 10‐5‐10‐3 U/ml respectively). Unlike FRTL‐5 cells, JPO9 cells respond well to unmodified serum and grow constitutively in the absence of TSH, thereby not requiring TSH deprivation prior to assay. The TSAb values obtained with both cell lines correlated well (r= 0·87). The JPO9 cells responded specifically to Graves' sera (23 out of 28 newly diagnosed patients were positive), whereas no patients with Hashimoto's thyroiditis and only 4 of 40 patients with non‐thyroid autoimmune diseases gave low positive results for the presence of TSAb.CONCLUSIONS The JPO9 cells provide similar diagnostic information to FRTL‐5 cells in patients with autoimmune thyroid disease. However, because they are more sensitive, grow faster, have less fastidious growth requirements and respond to unextracted sera, compared to FRTL‐5 cells, we conclude that the JPO9 cells are preferable for the measurement of TSAb.
Reversibility of physiological growth hormone secretion in children with psychosocial dwarfism
Authors: Albanese A. , Hamill G. , Jones J. , Skuse D. , Matthews D. R. , Stanhope R. 
Published: March 2008

OBJECTIVES Reversibility of GH insufficiency with a change of environment is characteristic of psychosocial dwarfism, and excludes an organic endocrinopathy. However, the change in GH pulsatility has not previously been described. We therefore wished to study spontaneous GH secretion before and after change to a more favourable environment in 11 children with psychosocial deprivation and short stature in order to evaluate if separation from the families can modify their patterns of GH secretion.PATIENTS AND DESIGN We describe 11 prepubertal children (6 M and 5 F; 2.2–13.5 years of age) who had growth failure and psychosocial deprivation. They were diagnosed by a multidisciplinary team as having environmental growth failure after admission to hospital for 3 weeks. Six of them were discovered to have been sexually abused. During the uninterrupted hospital admission parental access was restricted. Three sets of 18‐hour GH profiles were performed on each child, except one child who had only two, during the 3‐week admission.MEASUREMENTS Pulse analysis of GH profiles was by Fourier transformation.RESULTS On the first day of admission spontaneous GH secretion demonstrated a spectrum of abnormalities in the pattern of basal values, pulse frequency and pulse amplitude. Such GH insufficiency showed reversibility during the 3 weeks in hospital. Indeed, there was a significant increase in GH secretion which was amplitude modulated without any significant modification in pulse frequency.CONCLUSION Our data indicate that there is abnormal physiological GH secretion in children with psychosocial deprivation, which is associated with growth failure. Despite a pathological situation, each child retained his own characteristic pattern of GH pulsatility. The pattern of reversibility of abnormal GH pulsatility provides information for the mechanism of the control of GH secretion.
Amylin/islet amyloid polypeptide expression in medullary carcinoma of the thyroid: correlation with the expression of the related calcitonin/CGRP genes*
Authors: Alevizaki M. , Dai K. , Grlgorakls S. I. , Legon S. , Souvatzoglou A. 
Published: March 2008

SummaryOBJECTIVE The amylin/lslet amyloid polypeptide (IAPP) gene is the third member of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene family, which includes the αCT/CGRP (CALC‐I) and βCGRP (CALC‐il) genes. CT is predominantly expressed in thyroid C cells, a and βCGRP (CGRP‐I and II) in neural tissue and amylin/IAPP in pancreatic β cells. Both the detailed tissue distribution and the physiological role of amylln are subjects of current research. We sought to characterize the RNAs transcribed from the IAPP gene In normal human pancreas and to investigate possible ectopic expression of this gene in neuroendocrine tumours.DESIGN AND TISSUES RNA was extracted from normal human pancreas, five phaeochromocytomas and 12 medullary thyroid carcinomas (MTCs) and studied by Northern blotting.RESULTS We found that in normal human pancreas the IAPP gene transcripts differ in size from those reported for human Insulinoma. Expression of the amylin/IAPP gene was detected In seven of the MTCs, while it was not detected in phaeochromocytomas. There were no apparent clinical or histological differences between IAPP positive and IAPP negative MTCs. The relative expression levels of the four mRNAs of the CT/CGRP gene family varied between the different tumours.CONCLUSIONS Our findings are consistent with the view that ectopic hormone production may occasionally be causally related to the common origin of related genes.The possibility that IAPP may constitute a minor component of MTC amyloid should be considered.
Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism
Authors: LoCascio Vincenzo , Braga Vania , Bertoldo Francesco , Bettica Paolo , Pasini Anna Fratta , Stefani Lucia , Moro Luigi 
Published: March 2008

SUMMARYBACKGROUND In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an aminoacid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery.METHODS Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit.RESULTS Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (−55 and −31% respectively). Twenty‐five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH.CONCLUSION Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.
Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism*
Authors: Kirk J. M. W. , Savage M. O. , Grant D. B. , Bouloux P‐M. G. , Besser G. M. 
Published: March 2008

SummaryOBJECTIVE This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism.DESIGN Analysis of male patients with IHH treated with hCG or combined hCG/hMG for a minimum of 6 months at St Bartholomew's Hospital. Clinical and endocrine assessment was performed in all patients prior to commencing therapy.PATIENTS A total of 26 males with IHH have been treated with exogenous gonadotrophins. Thirteen patients (Group 1) had cryptorchidism (unilateral in 7, bilateral in 6) at presentation, and 13 (Group 2) did not.MEASUREMENTS All patients had basal serum testosterone, LH and FSH determinations. An i.v. GnRH test was performed in 25 patients and an i.m. hCG stimulation test in 19. Testicular volume and serum testosterone were measured during both hCG and combined hCG/hMG therapy. Seminal analysis was performed at the start and monthly during hCG/hMG therapy.RESULTS Eighty‐five per cent of the 13 patients in Group 1 had an olfactory defect (Kallmann's syndrome), compared with 23% of Group 2. Both groups of patients showed a subnormal response to initial i.v. GnRH and i.m. hCG testing. During hCG therapy only three patients in Group 1 and six In Group 2 achieved normal adult testosterone levels. The non‐cryptorchid group achieved a higher mean testicular volume on hCG therapy than the cryptorchid group (mean (SD); 4.7 (1.8) ml vs 3.0 (1.6) ml (P < 0.02)), and for all patients there was a correlation between initial and maximal testicular volume (R = 0.69, P = 0.001). Four patients in Group 1 and five patients in Group 2 were treated with combined hCG/hMG tor 6–15 months to induce fertility; only one patient in Group 1 achieved spermatogenesis, compared to all patients in Group 2 (leading to three pregnancies).CONCLUSIONS These data indicate that patients with idiopathic hypogonadotrophic hypogonadism (IHH) have a poor response to hCG therapy in terms of testicular growth and normalization of serum testosterone. Final testicular volume is dependent on Initial testicular size. In addition, patients with IHH associated with cryptorchidism have a poor fertility potential to combined hCG/hMG therapy.
The ratio between serum levels of insulin‐like growth factor (IGF)‐I and the IGF binding proteins (IGFBP‐1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients
Authors: Juul Anders , Main Katharina , Blum Werner F. , Lindholm Jorgen , Ranke Michael B. , Skakkebaek Niels E. 
Published: March 2008

SummaryOBJECTIVE Several in‐vitro studies have suggested that the biological actions of IGF‐I can be modified by the presence of specific IGF binding proteins. In man, the 24‐hour serum levels of IGF‐I and IGFBP‐3 remain constant, but short‐term changes in the IGF‐l/IGFBP‐3 ratio have been described following GH administration. Serum levels of IGF‐I and IGFBP‐3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF‐I and IGFBP‐3 in acromegalic and healthy adults have not been described previously.METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mLU/l II GH 2–10mLU/l; III GH > 10mLU/l). In all subjects a single blood sample was drawn for IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3 and GH measurements by specific RIAs. In 38 of the patients a 24‐hour urinary collection was performed for GH determination.RESULTS In healthy adults serum levels of IGF‐I and IGFBP‐3 decreased with Increasing age (r =−0.52 and r=−0.34, respectively, P< 0.0001). In addition, the molar IGF‐l/IGFBP‐3 ratio declined with increasing age (r =−0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF‐I was increased 7–97 standard deviations (SDS) and IGFBP‐3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF‐II were normal in all three groups (588 ± 240μ/l) whereas IGFBP‐1 and IGFBP‐2 levels were low and IGFBP‐2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF‐l/IGFBP‐3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001).CONCLUSION We demonstrated a decreasing molar IGF‐l/IGFBP‐3 ratio with increasing age in healthy adults and an increased ratio between serum IGF‐I and IGFBP‐3 levels in acromegalic patients. As IGF‐II is normal and IGFBP‐1 and IGFBP‐2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF‐I and IGFBP‐3 reflects free (biologically active) IGF‐I and Is dependent on GH levels.