bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human plasma melatonin and urinary 6‐sulphatoxy melatonin:studies in natural annual photoperiod and in extended darkness
Authors: Matthews C. D. , Guerin M. V. , Wang X. 
Published: March 2008

Summary. Objectives The alms of the study were (1) to examine the human plasma melatonin rhythm at the equinoxes and the solstices in the natural photoperlod (35.S); (2) to examine melatonin rhythms in the same subjects under extended darkness conditions to expose any suppressive (gating) effects of light at any time of the year; (3) to undertake a rigorous examination of the relationship between plasma melatonin and the urinary metabolite 6‐suiphatoxy melatonin at varying times of the year.Design At the equinoxes and solstices, unrestricted subjects had hourly urine collections followed by venous blood sampling taken under natural light conditions for 24 hours. Following a 24 hour Interval, a similar collection regime was performed with subjects held under conditions of extended darkness (5 hours darkness prior to natural sunset and following natural sunrise) for a further 24 hours.Subjects Groups of four (minimum) to six female volunteers (age range 18–35 years) were studied, who had a normal lifestyle, no history of depression, and were not taking any medication or recently engaged in shiftwork.measurements The plasma was assayed for melatonin and the urine samples for 6‐suiphatoxy melatonin by radioimmunoassay.results The onset of natural melatonin secretion was delayed until after sunset at all seasons but was earlier In summer, and not different from the time of sunset in extended darkness. The offset of melatonin secretion under natural conditions occurred at sunrise in autumn and winter but was delayed until after sunrise during spring and summer, particularly in extended darkness.No significant changes in the duration of melatonin secretion were observed between seasons nor between the duration of melatonin secretion under natural photoperiod or extended darkness.The measurement of 6‐suiphatoxy melatonin proved to be a close Indicator of the phase and amplitude of secretion of plasma melatonin. Both onset and offset times of 6‐sulphatoxy melatonin were delayed compared to the times when plasma melatonin was detectable/undetectable. A good correlation exists between the total plasma melatonin secretion and that of 6‐sulphatoxy melatonin.conclusions The results suggest evidence for a suppressive(gating) effect of light at dawn only during summer which was associated with a phase advance of the onset of melatonin secretion at this time of year. The lack of a major gating effect of environment light on melatonin secretion, and the unchanging duration of secretion through the year In the normally entrained human, highlight differences between the human and those photoperiodic animal species which breed seasonally.Urinary 6‐suiphatoxy melatonin proved to be a good Indicator of plasma melatonin levels under rigorous examination and Is confirmed as a useful clinical measure.
The use of venous catheterization in the diagnosis and localization of bilateral phaeochromocytomas
Authors: Newbould E. C. , Ross G. A. , Dacle J. E. , Bouloux P. M. G. , Besser G. M. , Grossman A. 
Published: March 2008

Summary. objective The purpose was to assess the value of venous catheter sampling as a method for the location of phaeochromocytomas, particularly when imaging techniques have been equivocal or ambiguous.design Venous catheter sampling was carried out in cases of suspected phaeochromocytoma, and compared with samples obtained from other patients without phaeochromocytomas undergoing adrenal venous catheterization.patients Three patients had phaeochromocytomas (subsequently confirmed by histology); five patients had no clinical or biochemical evidence of phaeochromocytoma but were being Investigated for other conditions. MEASUREMENTS Catecholamlne and cortisol assays were performed on plasma samples from the adrenal veins and elsewhere, and the noradrenallne to adrenaline (NA:AD) ratio was calculated.results In patients without phaeochromocytomas the NA:AD ratio was < 1 In nine adrenal vein samples; In four adrenal vein samples with NA:AD ratio of > 1, the presence of a phaeochromocytoma was subsequently confirmed. An extra‐adrenal tumour was also located by comparison of central and peripheral venous catecholamine concentrations.conclusions Venous catheterization with measurements of catecholamines, and determination of NA:AD ratios, allows for the rapid and confident diagnosis and localization of unllateral, bilateral, and extra‐adrenal phaeochromocytomas.
Nocturnal melatonin secretion in thyroid disease and in obesity
Authors: Röjdmark S. , Berg A. , Rössner S. , Wetterberg L. 
Published: March 2008

Summary. objective The purpose was to Investigate whether the function of the pinealocytes is changed in patients with disturbed metabolic rate or In subjects with marked obesity.design Venous blood was sampled every second hour between 1800 and 0800 h, and urine collected between 2200 and 0700 h.patients Eight patients with thyrotoxicosis, six with primary hypothyroidism, eight with maturity‐onset obesity, and 12 healthy controls were Included In the study. MEASUREMENTS Peak serum melatonin values during the night, total nocturnal melatonin secretion (estimated by melatonin incremental areas), and urinary excretion of melatonin were determined in each participant.results Patients with hypothyroidism were found to have higher peak serum melatonin values, total nocturnal melatonin secretion, and urinary excretion of melatonin than normal individuals (Peak melatonin values: 0.55 × 0.13 vs 0.27 × 0.04 nmol/l, respectively; P < 0.05. Melatonin incremental areas: 3.38 × 0.80 vs 1.45 × 0.26 nmol/1 h; P < 0.05. Melatonin excretion: 0.140 × 0.023 vs 0.081 × 0.013 nmol/9 h; P < 0.05). Neither of these values differed significantly from the normal In patients with thyrotoxicosis or obesity. Although thyrotoxic patients thus released a normal amount of melatonin during the night, their melatonin secretion peak was phase advanced (melatonin secretion peak appearing at 1.1 × 0.5 h In thyrotoxic, and at 3.4 × 0.5 h in normal participants; P < 0.01). No such phase shifts were seen in patients with obesity or hypothyroidism.conclusions These findings imply that both hypothyroid and thyrotoxic patients have disturbed pineal function, which is not the case in patients with obesity. The mechanism underlying these observations remains to be elucidated.
Control of immunoactive inhibin production by human granulosa cells
Authors: Hillier S. G. , Wickings E. J. , Illingworth P. I. , Yong E. L. , Reichert Jr L. E. , Baird D. T. , McNeilly A. S. 
Published: March 2008

Summary. objective The aim was to determine the relation between stage of antral follicular development and granulosa cell production of immunoactive inhibin.design Primary granulosa cell cultures In serum‐free Medium 199 were Incubated at 37°C for 96 hours with a change of medium at 48 hours. Inhibin and steroid levels in culture medium were determined by radlolmmunoassay. The Inhibin assay was based on the N‐terminal 1–26 amino acid sequence of the α‐chain of porcine 32 kDa inhibin using plα1–26‐GLY27‐TYR28 as the immunogen, tracer and standard.patientsGranulosa cells were obtained from the ovaries of women with regular menstrual cycles undergoing hysterectomy with unilateral or bilateral oophorectomy to treat non‐malignant gynaecological disease.results Basal production of immunoactive Inhibin by granulosa cells from presumptive preovulatory follicles (> 15 mm diameter) was 5–13 times higher than that by granulosa cells from immature (< 10 mm diameter) or intermediately mature (10–15 mm diameter) follicles. Basal production of progesterone and oestradlol followed a qualitatively similar pattern, establishing a positive relation between functional granulosa cell maturity and inhibin production. Treatment of granulosa cell cultures from Immature follicles with follicle‐stimulating hormone (FSH), but not luteinizing hormone (LH), increased inhibin production, time and dose dependently. FSH, but not LH, also brought about similar Increases in steroid hormone synthesis by granulosa cells from immature follicles. The stimulatory effect of FSH on granulosa cell inhibin production was augmented at least twofold by the presence of testosterone or 5α‐dihydrotestosterone (1.0 μmol/I) but was unaffected by oestradiol. Granulosa cells from intermediately mature follicles undertook variable degrees of both FSH and LH‐responsive inhibin production which generally corresponded with gonadotrophin‐responsive steroid production. Granulosa cells from presumptive preovulatory follicles showed inconsistent inhibin responses to FSH. However, LH caused marked (at least twofold) Increases in inhibin production, paralleling LH‐responsive steroid production.conclusion These results show that for human beings, granulosa cell capacity to produce immunoactive inhibin in vitro increases with follicular maturity. FSH, but not LH, stimulates inhibin production by immature granulosa cells and this response to FSH Is subject to modulation by androgen. During preovulatory follicular development, production of inhibin, like steroids, becomes increasingly responsive to LH. Such a development‐related pattern of granulosa cell inhibin production helps explain how, post‐ovulation, the corpus luteum is able to secrete inhibin as well as steroids. It is also compatible with the concept that locally produced inhibin could participate In the paracrine control of follicular development during the human menstrual cycle.
Cholinergic blockade with pirenzepine induces dose‐related reduction in glucose and insulin responses to a mixed meal in normal subjects and non‐insulin dependent diabetics
Authors: Bevan J. S. , Ara Jamal , Page M. D. , Scanlon M. F. , Peters J. R. 
Published: March 2008

Summary. objective The aim of the study was to assess the effects of chollnerglc blockade with pirenzepine on glucose and Insulin responses to a mixed meal In normal subjects and patients with non‐insulin dependent diabetes (NIDDM). Further, to assess In normal subjects the relative Importance of nocturnal GH suppression by plrenzepine.design Placebo, 100 or 200 mg pirenzepine were given to the normal subjects 1 hour before a standard mixed meal. The effects of placebo or 200 mg pirenzepine at night on nocturnal GH secretion and subsequent breakfast carbohydrate tolerance were also studied. NIDDMs were given placebo or 200 mg pirenzepine before the meal.subjects We studied six healthy male volunteers (ages 20–22, body mass Indices 20.3–23.3) and ten NIDDMs (eight men, ages 42–74); five obese (BMI 25.5–31.8) and five non‐obese (BMI 21.2–24.8).measurements Serial plasma glucose and Insulin concentrations were measured for 3 hours after a standard mixed meal.results Acute pretreatment of normal male volunteers with plrenzepine produced a dose‐related Improvement in carbohydrate tolerance. Peak post‐prandial plasma glucose levels were delayed and significantly reduced following 200 mg orally (6.5±0.1 mmol/l), but not following 100 mg (7.3±0.3), compared with placebo (7.6±0.3). Peak insulin levels were similarly delayed and reduced by the 200 mg dose only (36.5±6.1 mU/l, compared with 49.8±8.7).Suppression of nocturnal GH by 200 mg pirenzepine at night produced a small reduction In fasting plasma glucose (5.0±0.1 mmol/l, compared with 5.3±0.1, p< 0.02) but did not Improve subsequent breakfast carbohydrate tolerance.Peak plasma glucose in NIDDMs was reduced following plrenzepine (12.4±0.9 mmol/l) compared with placebo (14.3±1.0, p<0.01). This reduction was equally significant in obese and non‐obese groups. Peak plasma insulin was also reduced by pirenzepine (22.4±3.9 mU/l) compared with placebo (42.4±5.3, p<0.01). Insulin suppression was quantitatively greater in obese than in non‐obese patients,conclusions Improvement in carbohydrate tolerance after plrenzepine in normal subjects is dose related and largely independent of GH suppression. Cholinergic blockade can also improve meal carbohydrate tolerance with simultaneous reduction in plasma Insulin concentrations In non‐insulin dependent diabetics, particularly those with obesity.
An association between hypothalamic‐pituitary dysfunction and peripheral endocrine function in extreme obesity
Authors: Weaver J. U. , Noonan K. , Kopelman P. G. 
Published: March 2008

Summary. objective The aim was to Investigate a possible relation‐ship between measures of Insulin secretion and glucose disposal and hypothalamic–pituitary function In extreme obesity.design A cross‐sectional analysis of obese subjects attending the Obesity Clinic at the Royal London Hospital and normal weight volunteers was undertaken. Investigations were performed on separate occasions and in random order.patients The subjects were 34 extremely obese women, menstruating and with normal glucose tolerance (mean Body Mass Index, BM1= 42) and 15 normal weight female controls (mean BMI = 22)measurements The following were measured: fasting insulin, relative Insulin resistance calculated using fasting Insulin and plasma glucose by the homoeostatic model of assessment, Insulin release during a 75‐g oral glucose tolerance test (insulin area under the curve), steady‐state plasma glucose level achieved during a simultaneous Intravenous Infusion of dextrose, insulin and somatostatin, and the prolactin and growth hormone (GH) responses to Insulin‐Induced hypoglycaemia.results In the obese group an Impaired prolactin response to hypoglycaemia (mean area under the curve obese 54 U/l min, controls 155 U/1 min; p=0.0001) was Inversely correlated to fasting insulin, r2=0.142, p=0.03; relative insulin resistance, r2=0.134, p=0.03 and steady‐state plasma glucose level, r2=0.345, p=0.0004 whereas the Impaired GH response (mean GH area under the curve obese 1.9 U/1 min, controls 65.7 U/1 min; p=0.0001) was Inversely correlated to steady‐state plasma glucose level, r2=0.196, p=0.01. Backward procedure for stepwise regression analysis confirmed the steady‐state plasma glucose level to be the most Important variable associated with the prolactin and growth hormone response among the remaining Indices of Insulin secretion/resistance.conclusion We conclude from these findings that hyperinsullnaemia In obesity Is an Important association with altered hypothalamic–pituitary function indicated by Impaired prolactin and growth hormone secretion to Insulin‐Induced hypoglycaemia.
Ovarian sensitization to gonadotrophins by human growth hormone. Persistence of the effect beyond the treated cycle
Authors: Burger Henry G. , Kovacs Gabor T. , Polson David M. , McDonald Jillian , McCloud Phillip I. , Harrop Malread , Colman Peter , Healy David L. 
Published: March 2008

Summary. objective To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses. DESIGN We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5–7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy.patientsWe studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea.measurementsWe measured body mass Index, FSH, LH, prolactin, growth hormone, insulin‐like growth factor I (IGF‐I), oestradiol and Inhibin at baseline and growth hormone, IGF‐I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75IU) and the last pre‐hCG dose of gonadotrophin used before, during and after growth hormone therapy.results Baseline growth hormone levels were low but IGF‐I levels were normal. IGF‐I Increased by 20% in the subject given 4 IU growth hormone, and by 50–100% in the other two. Pretreatment dally gonadotrophin dosage of 8–11 ampoules pre‐hCG was reduced to 3–6 ampoules during growth hormone and 3–4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject.conclusion Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs
GH response to growth hormone releasing hormone and hypoglycaemia is unaltered by high endogenous plasma calcitonin levels in patients with medullary thyroid carcinoma
Authors: Popovic V. , Micic D. , Damjanovic S. , Durbaba M. , Pelakov M. , Zorlc S. , Djurovic M. , Manojiovlc D. , Micic J. 
Published: March 2008

Summary. objective As it has previously been reported that calcitonin suppresses stimulated growth hormone release, we have studied the serum growth hormone response to growth hormone releasing hormone and insulin‐Induced hypoglycaemia In patients with high calcitonin levels due to medullary carcinoma of the thyroid. DESIGN Growth hormone releasing hormone (100 μg i.v.,) and insulin (0.15 units/kg i.v.) were given and the growth hormone responses in the patients with medullary carcinoma of the thyroid and normal healthy controls were compared.patientsEight with hlstologically confirmed medullary thyroid carcinoma, two females and six males, aged 21–77 years, were studied and compared with seven healthy age and sex matched controls.measurementsGrowth hormone and calcitonin were measured.resultsNo significant difference was found between the growth hormone responses observed in patients with medullary carcinoma when compared with normal controls either after GHRH or during Insulin‐Induced hypogiycaemia.conclusionWe conclude that calcitonin does not alter the pituitary response to GHRH in medullary thyroid carcinoma and Is unlikely to play an important role in regulating growth hormone secretion because calcitonin did not modify the release of growth hormone after Insulin‐induced hypoglycaemia.
Biochemical and hormonal changes induced by one week of administration of rIGF‐I to patients with Laron type dwarfism
Authors: Laron Z. , Klinger B. , Jensen L. T. , Erster B. 
Published: March 2008

Summary. objective The purpose of this investigation was to evaluate the effectiveness of short‐term administration of recombipant bfosynthetfc IGF‐I on patients with an hereditary inability to generate this hormone.design and patients Ten patients with Laron type dwarfism (LTD) (4 males, six females) aged 3° to 37° years were submitted to seven daily s.c. Injections of recombinant IGF‐I in doses of 120 or 150 μg/kg/day.measurementsBlood samples were drawn before, after three and seven Injections, and one week after stopping the trial.results The main biochemical and hormonal changes registered were (mean ± SD): a marked rise in serum type III procollagen (PIHNP) from 4.2±0.9 to 7.3.2 μg/l (P < 0.0003) and decrease in the following blood components: plasma hGH from 32.51±43.77 to 4.02±2.48 mU/I (P < 0.001), serum cholesterol from 5.9±1 to 5.7±0.8 mmol/l (P < 0.04), serum SGOT from 28.9±11.6 to 15.5±7.6 U/I (P < 0.01) and serum LDH from 286.88 to 222.37 U/I (P 0.0005). The response of plasma insulin was variable, decreasing in seven of ten and Increasing in three. Some of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIIINP).conclusionsIGF‐I mlmics the biochemical and hormonal changes described after administration of hGH. The administration of IGF‐I In patients with Laron type dwarfism is devoid of side‐effects and warrants assessment in long‐term studies.
Effects of hypo or hyper‐thyroidism on growth hormone‐binding protein
Authors: Amit Tamar , Hertz Pnina , Ish‐Shalom Sophia , Lotan Rachel , Luboshitzki Raphael , Youdim Mousse B. , Hochberg Zeev 
Published: March 2008

Summary. objective Growth hormone (GH) receptors are Influenced by the thyroidal state of experimental animals. It has been suggested that GH‐binding protein (BP) might serve as an Indirect measure of the GH receptors. The present study was undertaken to investigate the growth hormone binding protein in patients with hypo or hyperthyroidism.patients Patients Included 42 adults with untreated hyperthyroidism (FT4 > 25 pmol/l; TSH < 0.15 mU/I) and 29 adults and three children with untreated hypothyroidism (FT4<10 pmol/I; TSH>15 mU/I).measurements Growth hormone binding protein was measured by a binding assay with dextran‐coated charcoal separation. The specific binding of 125I‐human GH (1 ng) obtained with 50 μl serum was expressed as a percentage of the total c.p.m.results Growth hormone binding protein specific binding In hypothyroid adults and children was significantly lower than In their respective controls in both adults and children (P < 0.001). In patients with FT4 levels > 40 pmol/I, the mean (.SEM) growth hormone specific binding (12.89±0.59%) was higher than in controls (P < 0.05). However, In 15 hyperthyroid patients with levels of FT4 of 25–40 pmol/l, the mean growth hormone binding protein specific binding (11.22 ± 0.76%) was not different from that In normal human subjects. The affinity constants (Ka) obtained by Scatchard analysis for the hypothyroid and hyperthyroid patients' sera were not significantly different from that for normal human sera. Binding capacity for the hypothyroid sera was significantly lower (P < 0.02), while that of hyperthyroid sera was Increased (P < 0.001).conclusionsGrowth hormone binding protein correlates positively with the thyroid status. It can be indirectly deduced that this reflects a similar relationship with the human GH receptor.
The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices
Authors: Engelhardt D. , Weber M. M. , Miksch T. , Abedinpour F. , Jaspers C. 
Published: March 2008

Summary. objective The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro.measurements After Incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0–2000 μM), radioactive metabolites were separated by thin‐layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium‐labelled precursors to products.results In vitro, ketoconazole showed a significant Inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20‐desmolase (IC50 2 μM), 16α‐hydroxylase (IC50 9 μM), 17α‐hydroxylase (IC50 18 μM), 18‐hydroxylase (IC50 28 μM), and 11 β‐hydroxylase (IC50 35 μM). In the tested concentrations ketoconazole had no Inhibitory effect on the 21‐hydroxylase, the 3β‐hydroxysteroid dehydrogenase and the 20‐hydroxysteroid dehydrogenase component of the C17,20‐desmolase enzyme system.conclusionsThe data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17,20‐desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states.