ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02435.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02436.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02437.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02438.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVELocally 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 cellsin vitro.DESIGNPrimary 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, PGE2and PGF2xon basal and human chorionic gonadotrophin (hCG) stimulated progesterone productionin 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.ATIENTSCorpora 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.RESULTSPGE2and 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 PGE2to PGF2synthesisin vitroby human luteal cells from endogenously incorporated arachidonic acid did not change significantly with corpus luteum age, with PGE2tending to predominate. Oestradiol treatment shifted arachidonic acid metabolism from the lipoxygenase towards the cyclo‐oxygenase pathway in cells isolated from ageing corpora lutea.CONCLUSIONSOestradiol, at relatively high concentrations, is a potent inhibitor of basal and hCG induced luteal cell steroidogenesisin 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 prod

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02439.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEAlthough there is evidence from cross‐sectional studies that percutaneous oestrogen administration protects against menopausal bone loss, few longitudinal data are available. We have examined the effect of 3 years' treatment with percutaneous oestradiol on total body calcium, spinal trabecular bone mineral density and radial bone mineral content in post‐menopausal women.DESIGNand PATIENTS Twenty‐nine post‐menopausal women, aged 37–55 years, who had undergone hysterectomy and had experienced the onset of menopausal symptoms within the previous 2 years, were studied before and for 3 years during hormone replacement with oestradiol implants, given at approximately 6‐monthly intervals.MEASUREMENTSTotal body calcium was measured by prompt gamma neutron activation analysis, spinal trabecular bone mineral density by quantitative computed tomography and radial bone mineral content by single‐photon absorptiometry.RESULTSThere was a significant increase in the mean total body calcium, spinal trabecular bone mineral density and radial bone mineral content over the 3 years of the study. The mean (± SEM) percentage change per annum was +2 4% (±0.8) for total body calcium (P<0 01), + 3.3% (±0.6) for spinal trabecular bone mineral density (P<0.001) and +12% (± 0.6) for radial bone mineral content (P<0 05).CONCLUSIONSPercutaneous oestradiol replacement therapy prevents menopausal bone loss and is associated with a sustained and significant increase in total body calcium, spinal trabecular bone mineral density and radial bone mineral content over a 3‐year treatment period. Oestradiol implants thus have skeletal effects comparable to those of oral or tra

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02440.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEFollowing the chance observation of congenital adrenal hyperplasia in a patient with Turner's syndrome we decided to evaluate the incidence of 21‐hydroxylase deficiency (21‐OHD) in patients with Turner's syndrome and in their relatives.SUBJECTSFifty‐two patients with Turner's syndrome (mean age ± SD 14.7 ± 5.6 years) and 26 relatives were studied.MEASUREMENTS17‐Hydroxy progesterone (17‐OHP) serum levels before and after i.m. administration of 0.25 mg of ACTH(1‐24) were evaluated in patients with Turner's syndrome and relatives. In Turner patients basal testosterone and dehydroepiandrosterone concentrations were determined. The results of ACTH tests were analysed according to HLA class I and II alleles of subjects.RESULTSThe baseline 17‐OHP was in the range of the classical form of 21‐OHD in one Turner patient, who had severe clitoral enlargement since birth. In 11 patients the stimulated 17‐OHP serum level was higher than in normal controls and similar to that found in 21‐OHD heterozygous subjects. Clitoral enlargement was significantly more frequent in patients with high stimulated 17‐OHP levels (P<0.001). The frequency of heterozygous‐type responses was higher in Turner subjects (1:4.6) than in the Italian population (1:47 for the classic form and 1:9.5 for the non‐classic form of the disease). In our patients the frequencies of HLA antigens and haplotypes, usually associated with 21‐OHD, were different compared to the controls. HLA‐B8, which is negatively associated to 21‐OHD, was less frequent in Turner patients than in controls and absent in those with an elevated 17‐OHP level. HLA‐B14, B22 and B35 were more frequent, though not significantly so, in Turner patients than in controls and even more so in the group with an elevated 17‐OHP level. The same investigations performed in 26 relatives of the Turner patients showed a high frequency of carriers of 21‐OHD and three subjects with the cryptic form of the disease.CONCLUSIONSAlthough in the literature there are only two reports of the association of Turner's syndrome and 21‐OHD, on the basis of our experience this association was more frequent, in the Italian population. Since some of the typical signs of 21‐OHD (short final stature, varying degrees of virilization, menstrual irregularities, amenorrhoea, infertility) in patients with Turner's syndrome could also be attributed to the chromosomal abnormality, it is therefore more difficult to diagnose 21‐OHD in Turner subjects. Adrenal function should be assessed, at least in the presence of clitoral enlargement, in patients with Turner's syndrome, particularly if their karyotype does not contain a Y chromosome. The hypothesis of the presence of cryptic Y chromosome material in these patients should also be considered.Correspondence: Dr Daniela Larizza, Clinica Pediatrica, Policlinico

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02441.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEA high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus.DESIGNCross‐sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects.SUBJECTSNineteen non‐obese, non‐diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects.MEASUREMENTSThe continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1‐hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta‐cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25‐dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects.RESULTSPHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1–9.8) mmol/l) than did controls (7.9 (7.1–8.9) mmol/l,P<0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8–85.4)) than in controls (113.7% (89.3–149.2),P<0.001); beta‐cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta‐cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5–106.4)vs120% (98.8–156.6) respectively,P<0.05). No significant correlations were found between insulin sensitivity and PTH (rs=−0.21), 1,25(OH)2D (rs=−0.14), ionized calcium (rs=–0.11) and inorganic phosphate (rs= 0.34). Beta‐cell function did not correlate with PTH (rs= 0.15), 1,25(OH)2D (rs= 0.04), ionized calcium (rs= 0.23) or inorganic phosphate (r,=− 0.35).CONCLUSIONInsulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta‐cell function are mor

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02442.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVENon‐insulin‐dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non‐insulin‐dependent diabetes from two different ethnic groups.DESIGNSubjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test.PATIENTSTwenty‐four glucose‐tolerant first‐degree relatives of patients with non‐insulin‐dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes.MEASUREMENTSInsulin, proinsulin, glucose and intermediary metabolites were measured during a 75‐g oral glucose tolerance test. Insulin sensitivity was assessed using a 15‐minute insulin tolerance test (0.05 units/kg).RESULTSAsian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 ± 17 vs 40 ± 6 pmol/l,P<0 05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 ± 9 vs 51 ± 4μmol/l,P<0.005), but fasting glucose and non‐esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements.The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non‐significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 ± 7 vs 139 ± 12μmol/l/min,P<0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 ± 11 vs 160 ± 11μmol/l/min).CONCLUSIONSFirst‐degree relatives of non‐insulin‐dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non‐insuli

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02443.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEGraves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA‐associated susceptibility in both races may occur at the HLA‐DQ loci. The aims of this study were to examine the HLA‐A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis.DESIGNHLA‐A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene.PATIENTSNinety‐seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls.MEASUREMENTSFrequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the χ2test.RESULTSHLA‐B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians.CONCLUSIONSThese findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Gra

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02444.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY