bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CLOSE CORRELATION BETWEEN THE INHIBITORY EFFECTS OF INSULIN‐LIKE GROWTH FACTOR‐I AND SMS 201‐995 ON GROWTH HORMONE RELEASE BY ACROMEGALIC PITUITARY TUMOURS IN VITRO AND IN VIVO
Authors: LAMBERTS S. W. J. , VAN KOETSVELD P. , HOFLAND L. 
Published: March 2008

SUMMARYIn the present study we compared the in‐vitro effects of IGF‐I and SMS 201–995 on GH release by cultured tumour cells obtained from seven acromegalic patients with the preoperative in‐vivo GH dynamics, including the acute response to 50μg SMS 201–995 subcutaneously. IGF‐I and SMS 201–995 inhibited GH release during a 24 h incubation in four and five of the seven tumour cell preparations, respectively. The inhibitory effect of SMS 201–995 was greater than that exerted by IGF‐I (P < 0.01). There was a close correlation between the in‐vitro inhibitory effects of IGF‐I and SMS 201–995 (P < 0.01). In addition, the acute inhibitory effect of 50 μg SMS 201–995 on circulating GH levels in vivo correlated with the inhibitory effects in vitro of both SMS 201–995 (P < 0.01) and IGF‐I (P < 0.05). The inhibitory effects of IGF‐I and SMS 201–995 on GH release in vitro were shown to be additive in two of four tumours. There was no relation between the in‐vitro effects of IGF‐I and/or SMS 201–995 and several in‐vivo parameters, including fluctuations in GH levels, sleep‐induced GH release, a paradoxical increase of GH in response to TRH, and the circulating IGF‐I and PRL levels. In conclusion: (1) there is a close correlation between the sensitivity of GH release by cultured human adenoma cells to IGF‐I and SMS 201–995. (2) There is also a close correlation between the in‐vivo inhibitory effect on GH release of SMS 201–995 and the in‐vitro inhibitory effects of both SMS 201–995 and IGF‐I. (3) A subgroup of acromegalic patients harbour pituitary tumours in which the qualitative regulation of hormone secretion is similar to that of normal GH secretion.
PROLACTIN AND LUTEINIZING HORMONE PROFILES OF CURED ACROMEGALIC SUBJECTS
Authors: ROELFSEMA F. , FRÖLICH M. , DE BOER H. 
Published: March 2008

SUMMARYThe 24‐h PRL and LH hormone profiles were analysed of 16 cured male acromegalic patients who had undergone selective transsphenoidal surgery 4‐9 years previously. Eight of these patients also underwent pituitary irradiation. Blood samples were taken at 20‐min intervals; the PRL and LH data were analysed with the cluster program, ARIMA modelling, cross‐correlation techniques, Fourier analysis, and cosinor analysis. About 10‐11 PRL and LH peaks were demonstrated for both non‐irradiated and irradiated patients. The absolute heights of PRL pulses and the mean valley levels were significantly greater for irradiated patients than for non‐irradiated patients, but the increment in amplitude did not differ. A significant diurnal rhythm for PRL was found for all non‐irradiated patients but for only one irradiated patient. LH pulse area and amplitude were lower in the group of irradiated patients. The incremental responses of LH and PRL to GnRH and TRH, respectively, were lower in irradiated patients than in non‐irradiated patients. During the night (0200‐0800 h) the number of PRL pulses decreased in non‐irradiated patients but not in irradiated patients. Pulse nadirs and amplitudes increased during the evening and night in non‐irradiated patients but were constant in irradiated subjects. Bivariate modelling of the data for 14 patients revealed significant cross‐correlations between LH and PRL pulses in nine subjects. This study demonstrates that the pulsatile secretion of PRL and LH in treated acromegalics is basically normal. Additional radiation therapy, however, may lead to damage of the hypothalamus, as reflected by the absence of a circadian PRL rhythm. A direct influence on the pituitary by radiation is indicated by the decreased magnitude of LH pulses and the diminished response of LH and PRL after injection of GnRH and TRH, respectively.
THE EFFECT OF CALCITONIN ON GROWTH HORMONE SECRETION IN ACROMEGALY
Authors: LOOIJ B. J. , ROELFSEMA F. , FRÕLICH M. 
Published: March 2008

SUMMARYTo determine whether human calcitonin inhibits GH secretion in acromegaly, as previously described for healthy subjects, the effect of an i. v. bolus injection of calcitonin or saline on GH levels in patients with active acromegaly was studied and compared to that of an i. v. bolus injection of the synthetic somatostatin analogue, octreotide. After the injection of calcitonin, GH levels decreased by 46% of initial values, whereas octreotide reduced GH levels by 87% and saline had no significant effect. Administration of calcitonin to acromegalics did not cause the transient rise in plasma PRL and TSH levels seen in normal subjects. Octreotide induced a decrease in plasma PRL in three out of seven patients. It is concluded that human calcitonin suppresses GH secretion in acromegaly, but not to normal levels; moreover the effect is less than that found for octreotide. In addition, acromegalic patients did not exhibit the PRL and TSH‐releasing activity of calcitonin found in normal subjects, while octreotide inhibited PRL secretion in some acromegalic patients.
INHERITANCE OF MINERALOCORTICOID EFFECTOR ABNORMALITIES OF HUMAN MONONUCLEAR LEUCOCYTES IN FAMILIES WITH PSEUDOHYPOALDOSTERONISM
Authors: WEHLING MARTIN , KUHNLE URSULA , DAUMER C. , ARMANINI DECIO 
Published: March 2008

SUMMARYIn‐vitro effects of aldosterone on intracellular sodium and potassium concentrations have been described for normal human mononuclear leucocytes (HML). After incubation for 1 h at 37|MoC, intracellular sodium and potassium in HML are significantly higher in the presence of 1.4 nM aldosterone than after incubation without aldosterone. As published earlier, these effects were absent in patients with pseudohypoaldosteronism. In the present paper, the families of seven patients with pseudohypoaldosteronism (index cases) were studied. In the first family, two siblings were affected by the disease and had a reduced number of mineralocorticoid (MC) receptors on HML. Intracellular sodium and potassium in HML from these patients did not show a response to 1.4 nM aldosterone. The parents, who were first cousins, had no history of disease and normal receptor data, but in the mother, the response of HML electrolytes to aldosterone was abnormal. In the second family, the mother of a child with pseudohypoaldosteronism, the mother's sister, and her son, had low numbers of MC receptors. Only the aunt of the index case had an uncertain history of the disease. The MC effector mechanism was abnormal in both children and both mothers studied. In a third family, the effector defect was present only in HML of the father. In three further families the abnormality of the effector mechanism was detected in HML of the patient's mother. These data suggest an autosomal dominant inheritance of pseudohypoaldosteronism with variable expression of the gene. The abnormality of the MC effector mechanism seems to be a more sensitive means than the determination of aldosterone plasma levels and MC receptor studies to identify gene carriers without clinical symptoms.
THE EFFECTS OF ACUTE EXERCISE ON PULSATILE LH RELEASE IN HIGH‐MILEAGE MALE RUNNERS
Authors: McCOLL E. M. , WHEELER G. D. , GOMES P. , BHAMBHANI Y. , CUMMING D. C. 
Published: March 2008

SUMMARYEvidence suggests that acute exercise and endurance training has a suppressive effect on the hypothalamic—pituitary—gonadal (HPG) axis in men and women. To determine if training and acute exercise influence the neuroendocrine regulation of the HPG axis in men we examined pulsatile LH release in six male endurance runners with a training volume of at least 80 km per week, and compared this with values in six age‐matched sedentary controls. Blood samples were obtained through an indwelling i.v. cannula from the subjects at 15‐min intervals for 6 h following 24 h without significant physical activity and again, in the runners, following 60 min of running at a speed equivalent to 5% below the anaerobic threshold. Mean LH pulse frequency and amplitude, as well as areas under the LH pulses and total LH curve, were calculated but only the mean post‐exercise area under the total LH curve area was significantly lower than basal values (P<0.05) following exercise compared with the resting values in runners. Other measures of LH release did not change with acute exercise. Basal and pre‐exercise testosterone levels were also measured and found to be at the lower end of normal men. The mean pre‐exercise serum testosterone levels were significantly higher than basal levels. Mean testosterone levels, mean pulse amplitude, and mean area under the LH curve were significantly lower in resting runners than in the controls. The data suggest that exercise induces a general lowering of LH levels but does not inhibit LH pulsatile release. An anticipatory increase in serum testosterone occurred before exercise.
EFFECTS OF INHIBITION OF CHOLESTEROL SYNTHESIS BY SIMVASTATIN ON THE PRODUCTION OF ADRENOCORTICAL STEROID HORMONES AND ACTH
Authors: MOL M. J. T. M. , STALENHOEF A. F. H. , STUYT P. M. J. , HERMUS A. R. M. M. , DEMACKER P. N. M. , VAN 'TLAAR A. 
Published: March 2008

SUMMARYSimvastatin, a derivative of lovastatin, is a potent inhibitor of cholesterol biosynthesis and may interfere with steroid hormone production, for which cholesterol is required. In a single‐blind, placebo‐controlled study, 24 patients with severe primary hypercholesterolaemia (mean serum cholesterol ± SD = 10.74 ± 1.59 mmol/l) were treated with simvastatin 40 mg per day for 8 weeks. Before and after treatment, the following parameters were evaluated: basal levels of ACTH, cortisol, androstenedione, dehydroepiandrosterone and 17‐hydroxyprogesterone; urinary excretion of free cortisol; the cortisol response after short‐term infusion of ACTH; the ACTH and cortisol response during insulin‐induced hypoglycaemia. Total serum cholesterol decreased by 35.0 ± 8.1% (P < 0.001) and low‐density lipoprotein (LDL) cholesterol by 39.8 ± 9.8% (P < 0.001); high‐density lipoprotein (HDL) increased by 9.2 ± 11.1% (P < 0.001). Basal levels of ACTH were higher after simvastatin (2.9 ± 1.9 pmol/1 vs 4.1 ± 2.9 pmol/l; P < 0.05) whereas basal levels of steroid hormones were not significantly changed. The excretion of free cortisol was unaltered. The peak cortisol after ACTH infusion was lower after treatment (0.87 ± 0.23 μmol/l vs 0.78 ± 0.10 μmol/l; P < 0.05), but was unaltered during insulin‐induced hypoglycaemia. We conclude that simvastatin lowers serum cholesterol without clinically relevant effects on the adrenocortical steroid hormone secretion and the hypothalamic‐pituitary‐adrenal axis.
EVALUATION OF TSH RECEPTOR ANTIBODY BY ‘NATURAL IN VIVO HUMAN ASSAY’ IN NEONATES BORN TO MOTHERS WITH GRAVES’ DISEASE
Authors: TAMAKI H. , AMINO N. , IWATANI Y. , TACHI J. , KIMURA M. , MITSUDA N. , ICHIHARA K. , TANIZAWA O. , MIYAI K. 
Published: March 2008

SUMMARYNeonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in‐vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves’ disease was evaluated by this ‘natural in‐vivo human assay’. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin‐binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL‐5 cells (thyroid‐stimulating antibody, TSAb). Further, the binding‐stimulation index (B‐S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5–10 days after birth) born to 20 mothers with Graves’ disease who had positive TBII and/or TSAb (FT4I: r= 0.825 for TBII, r= 0.908 for TSAb, r= 0.944 for the B‐S index, P > 0.001; FT3I: r = 0.622 for TBII, P > 0.01, r= 0.812 for TSAb, r= 0.791 for the B‐S index, P > 0.001; n= 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves’ disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B‐S index and FT4I found in neonates was applied to values in adult patients with Graves’ disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B‐S index. FT4I and the ratio of FT4I to the B‐S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B‐S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B‐S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves’ disease (r=−0.288, P >0.05). The results suggest that in‐vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves’ disease may be regulated not only by circulating thyroid‐stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.
OSMOREGULATION OF THIRST AND VASOPRESSIN SECRETION IN KALLMANN'S SYNDROME
Authors: THOMPSON C. J. , WHITE M. C. , BAYLIS P. H. 
Published: March 2008

SUMMARYIt has been suggested that abnormalities of thirst and vasopressin secretion commonly coexist with Kallmann's syndrome. Out‐patient plasma osmolality, plasma sodium and 24‐hour urine volume were similar in 10 patients with Kallmann's syndrome and 10 matched controls. Six patients underwent dynamic testing of osmoregulation with hypertonic sodium chloride infusion. There were similar rises in plasma AVP concentration in patients (0.4 ± 0.1–6.2 ± 1.2 pmol/l, P > 0.001) and controls (0.4 ± 0.1– 5.7 ± 1.0 pmol/l P > 0.001). Thirst ratings rose in similar fashion in patients (0.7 ± 0.3–6.2 ± 1.0 cm, P > 0.001) and controls (1.0 ± 0.3–7.2 ± 0.5 cm, P > 0.001). Drinking rapidly abolished thirst and lowered AVP concentrations in both groups before major changes in plasma osmolality occurred. Linear regression analysis defined similar osmotic thresholds for thirst onset and vasopressin release in the two groups, and there was no difference in the calculated sensitivity of the osmoreceptor/vasopressin secretory unit as defined by the slopes of the regression lines. We conclude that osmoregulation is normal in Kallmann's syndrome.
PROLACTINOMAS PRESENTING AS PRIMARY AMENORRHOEA AND DELAYED OR ARRESTED PUBERTY: RESPONSE TO MEDICAL THERAPY
Authors: HOWLETT T. A. , WASS J. A. H. , GROSSMAN A. , PLOWMAN P. N. , CHARLESWORTH M. , TOUZEL R. , REES L. H. , SAVAGE M. O. , BESSER G. M. 
Published: March 2008

SUMMARYFourteen patients presented with arrested pubertal development associated with prolactin‐secreting pituitary tumours; serum prolactin ranged from 4000–104300 mU/1 in the ten females and 920–68000 in four males. Skull X‐ray showed a markedly expanded pituitary fossa in eight patients. CT scan and/or air encephalography showed macroadenomas in nine, of whom seven had large suprasellar extensions to their tumours, yet only five had complained of headache and only two had visual field defects. All were treated with bromocriptine (7.5–60 mg/day) which lowered prolactin substantially in all and into the normal range in 11 (range < 60–3090, median 105 mU/1). Puberty thereafter progressed spontaneously in 13, but in one patient, whose prolactin did not suppress completely, menarche could be induced only with clomiphene. Anterior pituitary function improved on bromocriptine. In seven patients with macroadenomas, tumour shrinkage into the pituitary fossa was complete and in two others incomplete shrinkage was followed by transsphenoidal hypophysec‐tomy. Seven patients received pituitary irradiation, six after bromocriptine‐induced shrinkage and one after transsphenoidal surgery. At follow‐up 6 months to 10 years (median 5 years) after presentation,' ten remain on bromocriptine with a suppressed serum prolactin, one has a normal prolactin after surgery, and three are off bromocriptine with residual hyperprolactinae‐mia (418–4680 mU/1). To date, four females have become pregnant and one male has fathered two children.Prolactinomas are an important, albeit rare, cause of arrested puberty and should therefore be sought. Most patients respond well to bromocriptine, with or without pituitary irradiation.
THE EFFECT OF OVINE CORTICOTROPHIN‐RELEASING FACTOR ON THE HORMONAL RESPONSE TO INSULIN‐INDUCED HYPOGLYCAEMIA
Authors: HOWLETT T. A. , GROSSMAN A. , McLOUGHLIN L. , PERRY L. , WHITE A. , COY D. H. , REES L. H. , BESSER G. M. 
Published: March 2008

SUMMARYIn order to investigate the role of hypothalamic corticotrophin‐releasing factor (CRF41) in the mediation of the pituitary ACTH response to hypoglycaemia, eight normal adult males were studied on four occasions. Commencing at 0830 h after an overnight fast, each received, in double‐blind, random order, intravenous boluses of: A, normal saline control; B, soluble insulin 0.15U/kg; C, ovine CRF41 (oCRF41) 100 μg; D, soluble insulin 015U/kg followed immediately by oCRF41 100 μg. Adequate hypoglycaemia (blood glucose < 2–2 mmol/1) was achieved in each subject when insulin was given alone or with oCRF41, and there was no difference in the glucose nadir between the 2 days. Peak plasma ACTH was significantly higher after insulin plus oCRF41 than after insulin alone (P<0.05) or oCRF41 alone (P<0.01) and this enhancement of ACTH release was most marked in the first phase of the response at 30 min (P<0.001, b vs d). There was no difference in the peak serum Cortisol response whether oCRF41 and insulin were given alone or together and although the area under the Cortisol curve was greater after insulin plus oCRF41, this difference was explicable simply on the basis of the earlier onset of the Cortisol response to oCRF41.There were no differences in the serum GH responses to hypoglycaemia on the 2 days. We conclude that during the initial, rising phase of the ACTH response to hypoglycaemia, secretion of hypothalamic CRF41 is not maximally stimulated and that changes in ACTH release are mediated by changes in another hypothalamic factor, the action of which is enhanced by simultaneous administration of a maximal stimulating dose of oCRF41.
INSULIN‐LIKE GROWTH FACTOR BINDING PROTEINS IN FOLLICULAR FLUID FROM NORMAL DOMINANT AND COHORT FOLLICLES, POLYCYSTIC AND MULTICYSTIC OVARIES
Authors: HOLLY J. M. P. , EDEN J. A. , ALAGHBAND‐ZADEH J. , CARTER G. D. , JEMMOTT R. C. , CIANFARANI S. , CHARD T. , WASS J. A. H. 
Published: March 2008

SUMMARYThere is now considerable evidence that the insulin‐like growth factors (IGFs) IGFs in ovarian physiology, the presence and functions of these IGFBPs will need to be characterized play an important role in the human ovary. It has also recently become apparent that the physiological activity of the IGFs is modulated by a number of specific binding proteins (IGFBPs). In order to understand the role of the. As an initial step towards this we have investigated the presence of the various binding proteins by Western ligand blotting and have measured the levels of one of them, IGFBP‐1, in follicular fluid (FF) obtained from unstimulated dominant and cohort follicles in 19 normal women and in eight patients with polycystic and one with multicystic ovaries. In normal women, IGFBP‐1 levels in dominant follicles were similar to matched serum levels but were significantly lower in cohort follicles. IGFBP‐1 levels correlated with FF‐volume (r= 0.58, P < 0.001) and with paired serum levels (r= 0.63, P < 0.001). In post‐LH surge dominant follicles this relationship with serum levels no longer held and in three out of nine subjects FF levels were higher than in serum. Thus IGFBP‐1 in normal human FF appears to be partly derived from the circulation but with additional local production in the larger developing dominant follicles. Western ligand blotting revealed five IGF‐binding proteins in FF running parallel with those identified in serum, suggesting that the IGFBP species previously identified in serum may also be present in FF. The two bands in positions corresponding to the components of the large (150kDa) binding complex were, as in serum, the predominant forms and in most FF samples these were even more prominent than in the accompanying serum sample. This contrasts with previous studies in lymph which suggested that the 150kDa complex was largely retained in the circulation. All three small IGFBPs varied considerably between FF samples even within an individual; each IGFBP varied independently of the other IGFBPs. Our results demonstrate that at least four discrete IGFBPs are present in FF and suggest that each may be produced independently within the ovary.
INOSITOL PHOSPHOLIPID TURNOVER AND INTRACELLULAR Ca2+ RESPONSES TO THYROTROPHIN‐RELEASING HORMONE, GONADOTROPHIN‐RELEASING HORMONE AND ARGININE VASOPRESSIN IN PITUITARY CORTICOTROPH AND SOMATOTROPH ADENOMAS
Authors: LEVY A. , LIGHTMAN S. L. , HOYLAND J. , MASON W. T. 
Published: March 2008

SUMMARYWe have studied the inositol phospholipid turnover response to thyrotrophin‐releasing hormone (TRH) gonadotrophin‐releasing hormone (GnRH) and arginine vasopressin (AVP) in five corticotroph and six somatotroph pituitary adenomas. GnRH (100 nM) increased inositol phospholipid turnover in five of five somatotroph adenomas tested by an average of 36.4 |Mp 9.4% (mean |Mp SE). In a fifth, which was too small to allow inositol phospholipid turnover to be assessed, GnRH produced a rapid increase in mean intracellular calcium ion concentration. Only one of five corticotroph adenomas responded to GnRH with an increase in inositol phospholipid turnover of 19%. In contrast, all the somatotroph and corticotroph adenomas tested (four of four and five of five respectively) increased inositol phospholipid turnover in response to AVP (100 nM), by an average of 61 |Mp 11.8% and 415 |Mp 186% respectively. The finding of an inositol phospholipid or intracellular Ca2+ response to thyrotrophin‐releasing hormone (TRH) (100 nM) in three of five somatotroph adenomas (Ca2+ increasing from 50 to 175 nM in one and inositol phospholipid turnover increasing by 172 |Mp 1.9% and 49 |Mp 5.2% in two) and to GnRH in all five somatotroph adenomas concurs with the common clinical finding of paradoxi‐cal growth hormone responses to these releasing factors in patients with acromegaly. The lack of such a response in three of the four corticotroph adenomas suggests that the appearance of GnRH and TRH receptors on adenomatous pituitary cells is not common to all cells.
THE CORTICOTROPHIN RELEASING HORMONE TEST IN LATE PREGNANCY: LACK OF ADRENOCORTICOTROPHIN AND CORTISOL RESPONSE*
Authors: SCHULTE HEINRICH M. , WEISNER DIETRICH , ALLOLIO BRUNO 
Published: March 2008

SUMMARYBiologically active corticotrophin‐releasing‐hormone (CRH) is produced by the placenta in large amounts and can be measured in the maternal circulation during third trimester of pregnancy. Its physiological significance is unknown. To further investigate the action of CRH in pregnancy, we performed a standard CRH‐test (1 μg/kg synthetic human CRH) in seven pregnant women 1 week prior to their calculated delivery data and 4‐5 weeks post‐partum. No response of plasma ACTH to CRH administration could be measured in any of the third trimester pregnant women. Post‐partum, basal ACTH levels were significantly lower (1.6 |Mp 0.3 vs 5.3 |Mp 0.2 pmo1/1) and reacted promptly to CRH administration (1.6 |Mp 0.3–4.2 |Mp 0.5 pmol/1; P < 0.05). Concentrations of cortisol in plasma and salivary cortisol paralleled the ACTH response to administration of CRH. However, one pregnant woman experienced physical and emotional stress during the CRH‐test and reacted with a sharp rise in cortisol secretion. The lack of the ACTH and cortisol response in this study to exogenously administered CRH in third trimester pregnancy may be due to high circulating glucocorticoid concentrations, desensitization of the pituitary corticotroph and/or in part due to circulating specific CRH‐carrier protein.