摘要:

SUMMARYPatterns of circulating prolactin bioactivity during three stages of the menstrual cycle were studied in detail in four normally cycling women. Serial blood samples were withdrawn at 10 or 15 min intervals for up to 8 h. Plasma prolaction concentrations were quantitated by a bioassay which is based on the replication of a rat lymphoma cell line (Nb2node) and by conventional radioimmunoassay. A total of 50–103 samples from each patient was analysed. Using a threshold‐based algorithm, definite pulsations of prolactin biological (B) and immunological (I) activity were detected at most stages of the menstrual cycle. The periodicity of these peaks ranges from 1 to 11/2 h. However, pulsations were less evident in one subject who had asymptomatic hyperprolactinaemia although circulating prolactin was fully bioactive (mean B:I ratios being 1 02–1.25). B:I ratios in the three normoprolactinaemic women were generally lower, ranging from 0.39±0.02 to 0–93±0.03. Elevations in the B:I ratio of normoprolactinaemic women were associated with bioactive peaks; this was not always the case in the hyperprolactinaemic subject. Thus, the lack of symptoms in this hyperprolactinaemic subject could not be due to bioinactive prolactin, but might perhaps be due to the absence of episodic prolactin secretion which would desensitise targ

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03248.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYClinical studies in patients with 21‐hydroxylase deficiency congenital adrenal hyperplasia (CAH) were designed to ascertain the genetics of the salt‐wasting component of the disorder. The gene controlling aldosterone biosynthesis may not be the same gene that controls 21‐hydroxylase in the adrenal zona fasciculata. This we infer from the following clinical observations: (1) concordance for salt‐wasting is not observed in all HLA‐identical sibs with CAH; (2) the defect in aldosterone biosynthesis does not persist throughout life as does the fasciculate defect; (3) there is a significantly increased gene frequency of B40 and Bw47 in salt‐wasting CAH; (4) obligate heterozygote parents of patients with salt‐wasting CAH do not express a partial defect in aldosterone biosynthesis, as they do in the fasciculata. These observations cast doubt on the accepted concept of the autosomal recessive transmission of the glomerulosa 21‐hydroxy

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03249.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYChronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5α‐dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D‐Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2±0.3 (SEM) to 1.1±0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43±0.04 to 0.030±0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26±0.03 to 0.03±0.01. In the same patients, serum testosterone levels were decreased from 3.91±0.51 to 0.14±0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032±0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03250.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYSensitive direct (non‐extraction) radioimmunoassays for assay of progesterone (Po) in saliva and capillary blood dried on filter paper have been developed to facilitate collection of specimens for the assessment of luteal function in the investigation of infertility. The antiserum had been raised to a Po I lα‐hemisuccinyl conjugate and the assays employ Po 11α‐glucurony 1‐[25I] tyramine as tracer with separation by solid phase double antibody. Po levels in saliva and capillary blood were compared with those in serum in matched specimens collected daily throughout the menstrual cycle from six female volunteers. The correlation between blood (y) and serum (x) Po levels (y= 0.439x‐2.98,r=0.98) was superior to that between salivary (y) and serum levels (x) (y=0.0637x+0.020.r= 0.89). Blood spot and serum Po levels were uniformly undetectable throughout the follicular phase, whereas in 2 out of 72 saliva specimens Po was inappropriately raised (60 and 120 pmol/l) possibly reflecting contamination of the specimens. Salivary and blood progesterone assays both lack adequate sensitivity to measure Po reliably in early or late luteal phases when serum levels are<12 nmol/l but are well suited to assess luteal function during the mid‐luteal phase of the cycle (4–10 d before menses) when serum levels in the six subjects ranged from 22–84 nmol/l, with corresponding blood levels of 6.2–35 nmol/l and saliva levels of 130–620 pmol/l. We conclude that blood spot and saliva Po levels both correlate well with Po levels in serum, but that blood spot Po lev

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03251.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe abnormal intermediate‐affinity T4 binding to albumin which is characteristic of familial dysalbuminaemic hyperthyroxinaemia (FDH) is dependent on buffer, temperature, and ionic composition. Scatchard analysis of T4‐binding to isolated albumin preparations from FDH subjects showed that half the circulating albumin showed the higher‐affinity T4 binding site, assuming one site per molecule. Using dextran‐charcoal separation at 40C the T4 affinity (Ka) of purified albumin from FDH subjects was 7.5 nmol/l in phosphate and 17 nmol/l in Tris‐CI‐ buffer. T4 binding to FDH albumin was inhibited by a range of substances in the order: 8‐anilino‐l‐naphthalene sulphonic acid>merthiolate>propylthiouracil>methyl‐thiouracil>carbimazole>salicylate>barbitone. Binding of T4 was competitively inhibited by low concentrations of dithiothreitol (DTT). The effect of DTT 0.1–0.5 mmol/l was reversed by removal of DTT by dialysis. Competition with a range of iodothyronines indicated that the 3′, 5′‐iodine atoms are most important for binding to this site. Serum binding of salicylate. frusemide. fenclofenac and barbituric acid, and a range of steroid hormones was similar in FDH and normal sera. Serum levels of sex hormone binding globulin (SHBG), were not significantly different from sex‐matched controls. Nuclear [125I]‐T3 binding sites in circulating lymphocytes from two FDH subjects showed affinities (Kd) of 59 and 79 pmol/l (normal 67±7 pmol/l,n= 6. These findings suggest that the highly specific binding anomaly of FDH is due to a disulphide‐dependent structural change in albumin. The normal T3 affinity of lymphocytic receptors and normal SHBG levels are consistent with a normal relationship between free

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03252.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYA radioimmunoassay (RIA) procedure was devised for the estimation of PRL in eluates of dried whole blood from filter paper. Levels of PRL were measured in newborn blood obtained during the first week of life from 530 infants of normal birthweight (>2500 g) with normal T4 values, 114 infants of normal birthweight with low T4 values (T4<6.0 μg/dl), 47 infants with congenital hypothyroidism, 57 infants of low birthweight (<2500 g) with normal T4 values, and 114 infants of low birthweight with low T4 values. Examination of PRL concentrations among comparably aged infants from the various groups revealed that the mean PRL values of the hypothyroid group were consistently greater than those of any of the other groups of infants regardless of the mean T4 levels. With the exception of the hypothyroid infants. the groups with both the lowest mean T4 concentrations and mean body weights also had the lowest mean PRL values

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03253.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYAbsorption of the diphosphonate etidronaEe (HEDP) was measured in 20 volunteer subjects at two centres (Glasgow and Madison) using a new method based on simultaneous administration of HEDP and intravenous99Tc‐HEDP (Osteoscan). The mean absorption of HEDP in fasting subjects in Glasgow was 3.5% (range 1–8.9%) and in Madison 1.5% (0.7–2.8%) (P<0.035). In four subjects studies were repeated with good agreement between results (mean 3.9 cf. 3.5%). Six subjects had studies repeated when drug was ingested with food and in all cases absorption was effectively reduced to zero. We conclude that absorption of HEDP is significantly higher in normal subjects in Glasgow than in Madison. This may be of importance with regard to the finding of histological osteomalacia and fracture associated with HEDP use in Gl

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03254.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYWe report an 8‐year follow‐up of three sisters born of a consanguineous marriage and who originally presented with short stature and enlarged pituitary fossa. All have shown progressive failure of anterior pituitary hormone function. In addition, the two eldest sisters were eventually found to have an empty sella while the youngest, who initially showed an enhancing intrasellar mass consistent with a tumour, later showed an empty sella. A familial pituitary tumour developing early in childhood but subsequently undergoing involution could account for these findi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03255.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThis study was designed to assess the effect of an altered level of serum oestrogen and progesterone on the prolactin (PRL) response to gonadotrophin releasing hormone (GnRH). Six normal women were studied in the early follicular phase and the mid‐luteal phase of one cycle and five menopausal women were studied before and after treatment with progesterone. Blood samples were collected at 15 min intervals for 6 h after a basal collection period of 30 min. Intravenous boluses of GnRH (1 μg, 10 μg and 50 μg) were given at 0, 2 and 4 h. Basal samples were assayed for 17β‐oestradiol (E2), oestrone (E1) and progesterone (P); LH, FSH and PRL were measured in all samples. Serum PRL was significantly elevated in all groups after 10 μg of GnRH with maximum increments (±SEM) ranging from 3.9±1.3 μg/l in early follicular phase women to 14.7 ± 4.7 μg/l in progesterone‐treated menopausal women. The PRL response to GnRH was significantly greater in the luteal phase and in menopausal women compared to early follicular phase women. There was a significant correlation between the maximum PRL response and the maximum LH response to GnRH in all the women studied (r= 0.7;P<0.01). A significant correlation was also found between the maximum PRL response and the basal serum oestrogen concentration in the normal cycling women (r= 0.8;P<0.01), but not when the menopausal women were included in the analysis. Administration of progesterone to menopausal women did not significantly affect the PRL response to GnRH and no significant correlation was found between the basal serum progesterone and the PRL response to GnRH. We conclude that GnRH stimulates the secretion of PRL in normal, cycling and in menopausal women to a degree which is more closely correlated with the LH response than with the circulating oestrogen or progesterone concentration. This is consistent with the hypothesis that GnRH exerts an indirect effect on the lactotrophe by stimulating the prodution of a paracrine factor from the gonadotrophe. We suggest that the action of GnRH on the lactotrophe may be physiological in view of its reported action in synchronizing the secretion of LH and PRL and in maintaining the acute releasable pool of PRL in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03256.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

SUMMARYThe distribution of TSH receptor antibody activity in the 7S and 19S fractions of Graves' sera has been re‐evaluated. Serum fractions were obtained by gel filtration from 12 Graves' sera and assayed for TSH receptor binding activity in a radioreceptor assay. Thyroid stimulating activity was determined in a cultured porcine thyroid cell bioassay. In apparent contrast to the findings of Bakeret al. (1983) TSH receptor binding activity was confined to the 7S gel filtration fraction, containing IgG, and was not detected in the 19S fraction, containing IgM. Similarly thyroid stimulating activity was detected only in the 7S fraction. 7S fractions from seven Graves' sera were fractionated by isoelectric focusing and the fractions analysed for TSH receptor binding activity and TSH agonist and antagonist activities. Five of the IgGs showed TSH agonist activity and in all five, the peak thyroid stimulating activity (measured by stimulation of cyclic AMP release from isolated porcine thyroid cells) was in fractions with a pI of between 8.0 and 9.5. In four of these five IgGs, TSH receptor binding activity showed similar isoelectric distribution to the thyroid stimulating activities. High levels of TSH receptor binding activity without associated TSH agonist or antagonist activity were however observed in some isoelectric fractions of the fifth stimulating Graves’IgG studied. All the isoelectric fractions from the fifth IgG with thyroid stimulating activities contained TSH receptor binding activity. Two of the Graves' IgGs showed TSH antagonist activity and both the TSH receptor binding and TSH antagonist activities of these IgGs showed similar isoelectric distribution with the peak activities at a pI of around 9.0. Consequently, it was not possible to separate TSH agonist or TSH antagonist activities from TSH receptor binding activity in seven Graves' sera by isoelectric focusing although in one IgG several isoelectric fractions contained isolated receptor binding activity. These findings are in keeping with the hypothesis that the biological activities of Graves' IgGs are intimately related to their ability to bind to the TSH recep

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1986.tb03257.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY