bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of oestrogen on progesterone synthesis and arachidonic acid metabolism in human luteal cells
Authors: Fisch B. , Rose M. P. , Elder M. G. , Winston R. M. L. , Margara R. A. , Hillier S. G. 
Published: March 2008

SummaryOBJECTIVE Locally produced oestrogens and prostaglandins (PGs) are implicated in the regulation of luteal lifespan in the human ovary. This study (1) assesses direct effects of these factors on progesterone synthesis in isolated luteal cells, and (2) explores interactions between luteal age and treatment with gonadotrophin or oestrogen on the metabolism of arachidonic acid (prostaglandin precursor) by steroidogenic luteal cells in vitro.DESIGN Primary monolayer cultures of human luteal cells obtained at different stages of the luteal phase were used to investigate the effect of oestradiol, catechol oestrogens (2‐ and 4‐hydroxyoestradiol), diethylstilboestrol, PGE2 and PGF2x on basal and human chorionic gonadotrophin (hCG) stimulated progesterone production in vitro. The role of PGs as modulators of luteal cell function was further investigated by studying the metabolic fate of radioactively labelled arachidonic acid in hormone treated (oestradiol and hCG) and control cultures, assessed by high performance liquid chromatography.ATIENTS Corpora lutea were enucleated from nine women with regular ovulatory cycles undergoing microsurgical reversal of tubal sterilization. Granulosa cell aspirates were obtained from three patients undergoing in‐vitro fertilization treatment.RESULTS PGE2 and PGF2α, at various concentrations did not have a consistent effect, whereas oestradiol, diethylstilboestrol (and 2‐hydroxyoestradiol in early luteal cell cultures) significantly inhibited basal and hCG stimulated progesterone biosynthesis. Evidence for direct inhibition of 3β‐hydroxysteroid dehydrogenase enzymic activity by oestradiol was obtained. Both major metabolic pathways of arachidonic acid (lipoxygenase and cyclo‐oxygenase) were operative in steroidogenic luteal cells recovered throughout the luteal phase. The ratio of PGE2 to PGF2 synthesis in vitro by human luteal cells from endogenously incorporated arachidonic acid did not change significantly with corpus luteum age, with PGE2 tending to predominate. Oestradiol treatment shifted arachidonic acid metabolism from the lipoxygenase towards the cyclo‐oxygenase pathway in cells isolated from ageing corpora lutea.CONCLUSIONS Oestradiol, at relatively high concentrations, is a potent inhibitor of basal and hCG induced luteal cell steroidogenesis in vitro. No support is provided for the concept that luteolysis is mediated by local production of PGF2α. The putative luteolytic effect of oestradiol may entail reduced metabolism of arachidonic acid to lipoxygenase derived products by luteal cells rather than direct stimulation of prostaglandin production by itself.
Transport of thyroxine into cultured hepatocytes: effects of mild non‐thyroidal illness and calorie restriction in obese subjects
Authors: Lim Chen‐Fee , Docter Roel , Krenning Eric P. , van Toor Hans , Bernard Bert , de Jong Marion , Hennemann Georg 
Published: March 2008

SummaryOBJECTIVE Inhibitors of cellular T4 transport leading to diminished plasma T3 production have been identified as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non‐esterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are responsible for the altered thyroid hormone parameters observed in mild illness and during calorie restriction.PATIENTS We studied (I) 18 non‐uraemic patients with non‐thyroidal illness (NTI) (T4 5±60, T3 ±1 1 and rT3 ±0 45 nmoI/I) with serum molar ratios of bilirubin:albumin ±0 17 and NEFA:albumin ±2 6. These molar ratios have been shown to be the minimum ratios which inhibited T4 transport into rat hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10–14 days. This diet is known to inhibit the unidirectional T4 transport into human liver in vivo.MEASUREMENTS We measured iodide production from 125I‐T4 by incubating rat hepatocytes with 10% human serum. The deiodination of T4 was used as an index of cellular transport of T4 in vivo.RESULTS The mean iodide production from 125I‐T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98±17%, mean±SD) was not significantly different from the normals (100 ±9%). Calorie restriction in euthyroid obese subjects resulted in a small but significant reduction (‐12%) of iodide production. Calorie restriction increased the total serum NEFA by 91 %.CONCLUSIONS Our study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in patients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calorie restriction inhibits T4 tissue uptake. This inhibition may partly explain the lower plasma T3 during calorie restriction.
Decreased psychological well‐being in adult patients with growth hormone deficiency
Authors: Rosén Thord , Wirén Lena , Wilhelmsen Lars , Wiklund Ingela , Bengtsson Bengt‐Åke 
Published: March 2008

SummaryOBJECTIVE Besides effects on body composition, bone mineral content and lipid metabolism, GH seems to influence quality of life, according to previous studies of limited numbers of patients with GH deficiency of childhood and adult origin. In this study psychological well‐being was assessed in a large number of patients with GH deficiency of adult origin.DESIGN A follow‐up study of patients with hypopituitarism on routine replacement therapy with l‐thyroxine, cortisone acetate and sex steroids.PATIENTS Eighty‐six patients (51 men, mean age 55.4 years and 35 women, mean age 54.9 years) diagnosed as having growth hormone deficiency on the basis of low IGF‐I concentration or a maximum GH response less than 5 mU/l after an insulin/glucagon tolerance test.MEASUREMENTS Quality of life was measured with a self‐rating questionnaire, the Nottingham Health Profile, and the results were compared with the results from 86 controls matched for age, gender, marital status and socioeconomic class. Furthermore, the observed and expected number of disablement pensions were calculated.RESULTS The mean total score of the patients was higher, i.e. worse (P<0.05), than that of the matching controls, indicating a higher level of perceived health problems among the patients. There were higher scores (poorer life quality) for energy (P<0.001), social isolation (P<0.01), emotional reaction (P= 0.056) and sex life (P<0.001) among patients compared with controls. Finally, the observed number of disablement pension among the patients tended to be higher than expected (19 vs 12.4, P= 0.09).CONCLUSIONS Adult patients with GH deficiency have a decreased psychological well‐being in terms of energy, social isolation and emotional reaction and a disturbed sex life compared with normals. Furthermore, there is a tendency to a higher frequency of early retirement.
Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha‐subunit and GH
Authors: Patrick A. W. , Atkin S. L. , MacKenzie J. , Foy P. M. , White M. C. , MacFarlane I. A. 
Published: March 2008

SummaryA 51‐year‐old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha‐subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.
Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNA‐sequences
Authors: Boucekkine C. , Toublanc J. E. , Abbas N. , Chaabouni S. , Ouahid S. , Semrouni M. , Jaubert F. , Toublanc M. , McElreavey K. , Vilain E. , Fellous M. 
Published: March 2008

SummaryOBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex‐reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex‐reversed individuals into three groups, Y‐DNA‐positive phenotypically normal XX males, Y‐DNA‐negative XX males with genital ambiguities and Y‐DNA‐negative true hermaphrodites can be applied to our cases.DESIGN Endocrinological and genetic studies were conducted in 20 XX sex‐reversed patients.PATIENTS Twenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46, XX true hermaphroditism in five, and XX male in 15.MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA, In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y‐specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods.RESULTS In this study, three categories of XX sex‐reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n= 9) or decreased (n= 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material.CONCLUSION Although the presence of Y‐specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y‐DNA‐negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non‐Y, testis‐determining genes.
Osmoregulation of vasopressin and thirst: comparison of 20% mannitol with 5% saline as osmotic stimulants in healthy man
Authors: Phillips E. M. G. , Butler T. , Baylls P. H. 
Published: March 2008

SummaryOBJECTIVE Osmoregulation is normally studied using a 5% saline Infusion. This may be deleterious in fluid overloaded patients. Twenty per cent mannitol is another osmotic stimulant. This study aimed to compare 20% mannitol infusion with 5% saline as an osmotic stimulant to thirst and vasopressin secretion in normal volunteers.DESIGN AND PATIENTS Eight healthy volunteers studied on 2 occasions in random order. Each study involved a 2‐hour Infusion period of either hypertonic (5%) saline (0·06 ml/kg/h) or hypertonic (20%) mannitol (0·07ml/kg/h).MEASUREMENTS Plasma vasopressin (pVp), plasma sodium, plasma osmolality (pOsm), haematocrit (HCT), blood pressure, thirst, blood glucose and volume drunk at end of infusion.RESULTS Five per cent saline infusion stimulated significantly higher levels of pOsm, pVp and thirst than 20% mannitol. Plasma sodium rose significantly during 5% saline infusion and fell during 20% mannitol infusion. HCT fell and mean arterial pressure rose in both infusions but the changes were not clinically significant. Plecewise linear regression analysis defined the overall threshold for pVp release for the two solutions as 5% saline, 292 mosm/kg and 20% mannitol, 291 mosm/kg, and the post threshold slope as 5% saline, 0·46 pmol/l pVp per mom and 20% mannitol, 0·30 pmol/l pVp per mosm. The threshold for thirst onset was 5% saline, 291 mosm/kg and 20% mannitol, 290 mosm/kg, and the post threshold slope, 5% saline, 0·58 cm thirst per mosm and 20% mannitol, 0·28 cm thirst per mom. The differences between the calculated osmotic thresholds and slopes post threshold for the two infusions were not significant for the pVp versus pOsm relationship. The difference between the cumulative volume drunk following the two infusions did not reach statistical significance. Mannitol caused a significant diuresls.CONCLUSIONS Twenty per cent mannitol infusion is an effective osmotic stimulant to thirst and vasopressin release in normal individuals, but is less potent than 5% saline Infusion.
Increased insulin sensitivity in patients with aldosterone producing adenoma
Authors: Ishimori Masatoshi , Takeda Noriyuki , Okumura Syouji , Murai Toshihiro , Inouye Hiroshi , Yasuda Keigo 
Published: March 2008

SummaryOBJECTIVE Primary aldosteronism is a recognized endocrine cause of glucose intolerance. A blunted insulin response to glucose in patients with primary aldosteronism is well known, but insulin sensitivity has not been thoroughly determined. We investigated insulin sensitivity and insulin secretion in patients with aldosterone producing adenoma.DESIGN Glucose tolerance and insulin responses to glucose were evaluated using a standard 75 g oral glucose tolerance test in patients with aldosterone producing adenoma before and after surgery, and in control subjects. Parameters for insulin resistance (HOMA‐R) and pancreatic β‐cell function (HOMA‐βF) were derived from a homeostasis model assessment.PATIENTS Fifteen patients with aldosterone producing adenoma and 41 control subjects with normal glucose tolerance matched for age and body mass index, were studied. Eight patients were re‐evaluated after surgical removal of the adenoma. In 5 patients 125I‐insulin binding to erythrocytes was also measured.MEASUREMENTS Plasma glucose was measured by a glucose oxidase method. Plasma insulin, aldosterone and renin activity were measured by radioimmunoassay.RESULTS Both fasting plasma glucose and insulin were lower in the patients than in the controls. Although the areas under the curve for plasma glucose during the oral glucose tolerance test did not differ, that for plasma insulin was less in the patients with hyperaldosteronism. Insulin sensitivity was increased in the patients, as evidenced by decreased HOMA‐R compared with controls, while HOMA‐βF was comparable between the groups. 125I‐insulin binding to erythrocytes was higher in 5 patients than in 19 normal controls. After surgical removal of adenoma, neither fasting plasma glucose nor the glucose area under the curve during the oral glucose tolerance test changed. However, fasting plasma insulin and the insulin area under the curve increased significantly. HOMA‐R increased and HOMA‐βF remained unaltered.CONCLUSION Insulin sensitivity was increased in untreated patients with aldosterone producing adenoma. Enhanced insulin receptor binding may contribute to this increased insulin sensitivity.
Development and validation of a radioimmunoassay for follistatin in human serum
Authors: Gilfillan Christopher P. , Robertson David M. 
Published: March 2008

SummaryOBJECTIVE Follistatin (FS/FSH‐suppresslng protein/activin‐bindlng protein) Is a single‐chain glycoprotein, structurally distinct from inhibin, that has been shown to have inhibin‐like activity in suppressing FSH secretion both in vivo and in vitro. The aim of these studies was to develop and validate a radioimmunoassay (RIA) for FS In human serum, and to describe the physiological variations of serum FS In humans.PATIENTS Serum was collected from normal men, and normal women In the follicular and luteal phases of the menstrual cycle. Clinical samples were also collected from male patients with hypogonadism, post‐menopausal women and pregnant women in the first, second and third trimesters.MEASUREMENTS A RIA for FS In human serum was developed using antisera raked against purified bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum were non‐parallel to purified bovine FS standard in the RIA. The addition of sodium dodecyl sulphate (SDS 0·05%) to the assay buffer resolved the non‐parallelism suggesting that the interference of serum in the RIA was an assay matrix effect. To characterize the serum FS immunoactivity further, serum was fractionated by gel filtration on Sephadex G‐100. At neutral pH, FS immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In 0·1 M HCI, a second peak of FS immunoactivity eluted in the molecular weight range 30–60 kDa consistent with the known sizes of FS. This suggested that FS was dissociating from a larger complex. Fractions taken from the low molecular weight region diluted in parallel with bovine FS In contrast with fractions from the high molecular weight region which were non‐parallel. It Is concluded that the non‐parallelism of human serum in the FS RIA is due to the binding of serum FS to an unknown high molecular weight factor. This interference is eliminated by the Inclusion of 0·05% SDS in the assay buffer. The RIA in 0·05% SDS has been applied to the description of the normal and pathophysiological varlations of FS In human serum.RESULTS There were no significant differences between FS levels In serum from hypogonadal men, normal women In the follicular phase of the menstrual cycle, post‐menopausal women and pregnant women from the first, second and third trimesters. FS levels in serum of women in the luteal phase of the menstrual cycle were significantly lower than all other groups. FS levels in normal men were significantly higher than those in both luteel phase women and women in the first trimester of pregnancy (P < 0.05).CONCLUSIONS These findings argue against a role for circulating follistatin in the control of gonadotrophin secretion and suggest that the gonads and/or conceptus are not the primary source of follistatin immunoactivity in serum. The lower follistatin levels in the luteal phase of the menstrual cycle remain unexplained.
Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men
Authors: Rudman Daniel , Drinka Paul J. , Wilsont Charles R. , Mattson Dale E. , Scherman Francis , Cuisinier Mary C. , Schultz Shiela 
Published: March 2008

OBJECTIVES It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free‐living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin‐like growth factor I (IGF‐I), serum testosterone, habitual physical activity and mobility.SUBJECTS Forty‐nine independent, community‐dwelling older men, and 49 men of similar age residing in two Veterans Administration extended care facilities. The age range was 58–95 years.MEASUREMENTS Serum IGF‐I and testosterone were measured by radioimmunoassay. Habitual physical activity in the independent men and mobility in the institutionalized men were estimated by standard instruments. LBM and bone status at nine skeletal sites were determined by dual X‐ray absorptiometry.RESULTS The BMD and TBBMC values of the free living men were 4–20% higher than those of the institutionalized men. In the independent old men, serum testosterone was the strongest predictor of BMD and TBBMC, while age was the only predictor of LBM. In the chronically institutionalized men, age, body weight and immobility were the strongest predictors of body composition, and testosterone was correlated only with femoral neck BMD.CONCLUSIONS In aging independent men, low levels of testosterone are associated with demineralization of the skeleton. Immobility and under‐weight are associated with the osteopenia of old men residing in nursing homes. In this cross‐sectional study of elderly men, there was no evidence of a relation of the somatotrophic axis to bone status or LBM, or of the gonadotrophic axis to LBM.
Serum thyreoglobulin: an early indicator of autoimmune post‐partum thyroiditis
Authors: Parkes A. B. , Black E. G. , Adams H. , John R. , Richards C. J. , Hall R. , Lazarus J. H. 
Published: March 2008

SummaryOBJECTIVE The aim of this study was to assess whether autoimmune thyroid damage in post‐partum thyroiditis was accompanied by a significant rise in the concentration of thyroglobulin in the serum and whether its measurement could be useful In the prediction of the risk and severity of an episode of post‐partm thyroid dysfunction.PATIENTS Fifty‐one women, who had taken part in a larger survey of post‐partum thyroiditis, were selected at random for this study. Fourteen women without elevated circulating thyroid autoantibodies and 21 with raised thyroid autoantibodies remained euthyroid throughout the post‐partum year. A third group of 14 women had raised thyroid autoantibody levels and showed one or more episodes of thyroid dysfunction during the course of the first year post partum.MEASUREMENTS Thyroid autoantibodies were measured by ELISA, free T3 and free T4 by the Amerlex M method and TSH by an immunoradiometrlc method. Serum thyroglobulin was measured by a method free from interference by circulating endogenous thyroglobulin autoantibodies. Thyroid ultrasonography was performed using a General Electric RT3600 scanner operating at 7.5 MHz.RESULTS Fourteen control women had a mean serum thyroglobulin concentration of 3.3 μg/l (SD 4.4; range <1–12jxg/l; 95% confidence interval up to 6.0μg/l). Twenty‐one thyroid autoantibody positive euthyroid women had a mean serum thyroglobulin level of 5.8 μgl I (SD 6.2; range <1–36 μg/l) which was not significantly different from that seen in the control group. Sixteen thyroid autoantibody positive women who showed one or more episodes of thyroid dysfunction during the postpartum period had a mean serum thyroglobulin of 31 μg/l (SD 24–8; range up to 88 μg/l) and this was significantly elevated compared with both the control and antibody positive groups (P < 0.001). Serum thyroglobulin concentrations at 3 months post partum correlated with the degree of post‐partum hypothyroidism (as indicated by the maximum TSH and the minimum free thyroxine concentrations post partum) and, in those cases where thyroid ultrasound examinations were performed, with the degree of lymphocytic infiltration of the thyroid gland.CONCLUSIONS The data presented in this paper confirm the destructive nature of post‐partum thyroiditis and indicate that the measurement of serum thyroglobulin concentration could assist in the identification of those women at risk of post‐partum thyroiditis.