摘要:

SummaryIn recent years the techniques of molecular and cellular biology have made it possible to begin to dissect the origins and behaviour of the ACTH‐secreting tumour cell. It is becoming apparent that these tumours represent undifferentiated neuroendocrine cells, and it may be that their peptide‐secreting properties may have no more sinister oncological significance. However, an autocrine role for β‐endorphin may confer a selective growth advantage on the POMC‐expressing cell. It is still not clear why glucocorticoids fail to inhibit the POMC gene in these extra‐pituitary tumours despite the presence of glucocorticoid receptors. This may not be resolved until the mechanism for inhibition of POMC by glucocorticoids in the normal pituitary is understood, although it is tempting to speculate that a mutation in the glucocorticoid receptor or a tissue specific interaction is responsible for the resistance of POMC observed in the ectopic ACTH syndrome.In studying the peptides secreted by the extra‐pituitary tumours responsible for the ectopic ACTH syndrome it would appear that direct measurement of ACTH precursors and comparison with the circulating concentrations of ACTH can give valuable information on the percentage of tumours which do not effectively process the ACTH precursors. However, far more data have to be collected on patients with occult tumours in order to identify whether this type of processing is tissue specific. Nevertheless, these studies provide useful insights into the mechanisms of intracellular signalling and regulation in such tumours which may identify unique pharmacological tools to inhibit ACTH secretion or more importantly t

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01765.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01766.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We determined the 17‐hydroxyprogesterone (17‐OH P) response to buserelin, a GnRH agonist, and its relation to ovarian volume in the patients with polycystic ovary syndrome (PCOS).DESIGN We compared 17‐OH P response to buserelin in a large group of patients with that In a control group of healthy women. We also investigated whether there is any relation between LH‐induced 17‐OH P production in response to buserelin and ovarian volume.PATIENTS Ten normal women and 31 women with PCOS were included in the study.MEASUREMENT Pelvic ultrasound examination by abdominal or vaginal transducer was performed. Serum basal levels of LH, FSH, free testosterone and 17‐OH P were measured by radioimmunoassay. 17‐OH P responses to both ACTH and buserelin were detected. Cortisol levels were measured before and after dexamethasone suppression.RESULTS The subcutaneous administration of 1 mg buserelin produced an increase in serum 17‐OH P, which peaked within 24 hours in all groups. The mean ±SEM level of 17‐OH P, 24 hours after buserelin stimulation in the women with PCOS (15.94 ±1.31 nmol/l) was significantly higher (P<0001) than in the control group (6 75±0 69 nmol/l). The women with PCOS had increases in 17‐OH P levels exceeding 10.15 nmol/l 24 hours after buserelin testing. The increased 17‐OH P responses to buserelin were unchanged by pretreatment with dexamethasone to suppress adrenal function. The 17‐OH P response was significantly related to ovarian volume (r= 0.53,P<0.01).CONCLUSIONS Our findings suggest that the serum 17‐OH P response to a 1‐mg subcutaneous test dose of buserelin may be a diagnostic and practical test for PCOS. Increased ovarian volume in PCOS may be responsible for the elevated 17‐OH P response to buserelin, a GnRH ag

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01767.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVES We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti‐androgen flutamide (2‐methyl‐N‐[4‐nitro‐3‐(trifluoromethyl)phenyl]‐propanamide).DESIGN AND SUBJECTS Ten women, aged 28‐35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH‐stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non‐SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3α‐diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles.RESULTS Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Galiwey score<7. No adverse side‐effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti‐androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3al‐diol G levels did not change during flutamide treatment.CONCLUSION Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women us

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01768.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We measured the changes in testosterone fractions in serum of normal men over a 24‐hour period, and determined whether they could be simulated on the basis of current understanding of the interactions betwen steroids and binding proteins in the blood.DESIGN Starting from between 0830 and 0930 h, blood samples were taken every 45 minutes for 25 5 hours.PATIENTS Five healthy males aged 26‐45 years. All participants worked on a hospital campus and while being sampled carried out their normal activities during waking hours.MEASUREMENTS The concentrations of testosterone (RIA) and albumin, and the percentage non‐sex hormone binding globulin‐bound testosterone (ammonium sulphate precipitation) and percentage free testosterone (rate dialysis), were measured on each sample. Cortisol (RIA) and sex hormone‐binding globulin (SHBG) (IRMA) concentrations were measured on every second sample, and that of corticosteroid‐binding globulin on two samples from each series.RESULTS In all participants the levels of free and non‐SHBG‐bound testosterone in early morning samples (near 0530 h) were significantly different from those taken before midnight (P<0 0005). Significant circadian rhythms (P<0 05) in the concentration of testosterone and in the level of the free fraction were detected in all participants, and in four of the five participants for the non‐SHBG‐bound fraction. The amplitude of the free testosterone rhythm (34 ± 2% of basal) was greater than that for testosterone itself (24 ± 3% of basal). The 24‐hour rhythm of the non‐SHBG‐bound fraction was similar to the total and free fractions except for the period 0330‐0900 h when the level of this fraction declined by 15‐45% over 1 5‐3 hours. This decline was coincident with the initial rise in the concentration of Cortisol. A decline of 10 5 ± SEM 1 0% in the concentration of albumin, and 12 0 ± 1 1 % in that of SHBG occurred when the mean ambulant and supine levels were compared; analysis indicated significant circadian rhythms in the concentrations of these proteins. Simulation was used to investigate possible causes for the circadian rhythms in free and non‐SHBG‐bound testosterone. Simulation results matched the measured data well in qualitative terms, but quantitatively there were differences.CONCLUSIONS Increasing saturation of the binding proteins following rises in testosterone production, and the small but significant changes in protein concentration, probably related to postural changes, were implicated as the major factors in the rhythm amplitude. However, the early morning decline in the non‐SHBG‐bound fraction was not explained by these factors. The rise in Cortisol concentration at this time is a probable cause. Alternatively, simulation suggests that a substance appearing in the early morning and competing with testosterone f

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01769.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The present study was performed to characterize the molecular heterogeneity of serum FSH in normal males and to investigate the possible influence of testosterone on serum FSH in androgen‐deficient men before and during testosterone administration.DESIGN AND PATIENTS Serum samples were taken at 10‐minute intervals between 0730 and 0830 h from nine healthy, eugonadal men and from eight men with primary hypogonadism (Klinefelter's syndrome). In the hypogonadal patients, sampling was performed before treatment (n= 8), 4‐5 days after the first and the third injection of 250 mg testosterone enanthate given intramuscularly at three‐weekly intervals (n= 6), as well as 3 months after the onset of therapy (n= 3). Sampling was repeated 7 days apart in two of the nine healthy volunteers.MEASUREMENTS Aliquots from the individual serum samples were pooled and fractionated by chromatofocusing in the pH range 6‐3. Immunoreactive FSH was measured by immunofluorimetric assay (IFMA) in each fraction and the individual serum samples. In each serum pool, bioactive FSH was determined by in‐vitro bioassay (rat Sertoli cell aromatase bioassay), testosterone by RIA and LH by IFMA.RESULTS After grouping the percentage of immunoreactive FSH recovered in the individual fractions into intervals of 0 5 pH units, significant differences between controls and patients were observed in the pH regions 4‐4.5, 5.5‐6 and 6‐6.5. No statistically significant changes in the isoform distribution of FSH were detected during therapy in the Klinefelter patients. A high degree of variability, which did not follow a common pattern, was observed in the isoform distribution of FSH within the same individuals, both in the hypogonadal patients during treatment and in the two normal men whose blood samples were taken on two different occasions.CONCLUSIONS Serum FSH is highly heterogeneous in normal and hypogonadal men. There is a spontaneous intra‐individual variability in the relative abundance of the different FSH isoforms in serum that may most probably be related to metabolic deglycosylation of FSH. Minor but significant differences in the molecular heterogeneity of serum FSH could be demonstrated in Klinefelter patients compared to normal men. These differences are not modified by administration of testosterone enanthate at doses achieving normal androgenization, suggesting that factors different from testosterone may modula

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01770.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone‐binding globulin (SHBG) and insulin‐like growth factor binding globulin‐1 (IGFBP‐1) in women with polycystic ovarian disease (PCOD).DESIGN Prospective.PATIENTS Ten women with PCOD admitted to a University Infertility Clinic.MEASUREMENTS Fasting blood samples for determination of hormone levels were taken during the follicular phase before and one month after laparoscopic ovarian electrocauterization.RESULTS One month after electrocauterization the serum mean ± SE LH levels had decreased from 14 4 ± 1 9 to 10 9 ± 1 1 U/l (P<0 05), while the serum insulin levels showed no significant change (10 3 ± 2 0 and 8 1 ±1 3 μ/l). The levels of IGFBP‐1 (33 9 ± 8 2 and 38 4 ± 13 7μg/l) and SHBG (48 ± 10 4 and 43 ± 5 7 nmol/l) showed no significant changes. Testosterone decreased from 3 9 ± 2 6 to 2 9 ± 0 3 nmol/l (P<0 001) and androstenedione from 15 0 ± 1 2 to 12 0 ± 1 5 nmol/l (P= 0 05). After electrocautery seven out of ten PCOD patients ovulated either spontaneously (n= 3) or with clomiphene citrate (n= 4), and two of them conceived.CONCLUSIONS Ovarian electrocautery leads to resumption of ovulatory cycles in some but not all PCOD patients. This effect seems to be mediated by reduction of serum LH and androgen levels, while the insulin‐driven pathway via SHBG and

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01771.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women.DESIGN A double blind placebo‐controlled protocol was designed to study seven subjects in the mid follicular phase of two non‐consecutive cycles. Two mg of exogenous melatonin or placebo were given at 1600 and 2000 h, and blood samples were collected every 10 minutes from 1800 to 2400 h for hormone determination.RESULTS Melatonin treatment caused a significant upward resetting of the pulsatile pattern of PRL in six out of seven subjects. Average maximal peak height was significantly increased (median 716 mlU/l (range 198‐1433) on melatoninvs324 mlU/l (212‐688) on placebo,P<0.001), nadir value (572 mlU/l (148‐1084)vs216 mlU/l (54‐580),P<0 001) and area under the peak (26352 mlU/l min (5904‐93672)vs12096 mlU/l min (2340‐33552), P<0 001), whereas peak number, amplitude and interpeak interval did not change significantly. TSH pulsatility was unaffected by melatonin administration in four out of six subjects. Distribution of LH patterns after melatonin was inhomoge‐neous: level of pulsatility was higher in two cases and reduced in three; group analysis did not therefore show significant variation of pulsatility parameters.CONCLUSIONS Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on indiv

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01772.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likelytosuppress hypothalamic somatostatin release.DESIGN The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 μg i.v. bolus). Study 2: GHRH (100 μg i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100μg i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3μg i.v. bolus) of GHRH.SUBJECTS Four groups of eight normal male subjects, ages 22–35 years, were randomly assigned to each protocol.MEASUREMENTS Growth hormone was measured by RIA at 15‐minute intervals.RESULTS Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100μg) or submaximal (3μg) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH.CONCLUSIONS Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be es

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01773.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children.DESIGN Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency.PATIENTS Fifty‐eight children aged 58‐16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal.MEASUREMENTS GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as<16 μ/l. The values for urinary GH excretion were compared to normal ranges (2 standard deviations from the mean), established in healthy schoolchildren of normal stature.RESULTS All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n= 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of‘normal’GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were Judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.CONCLUSION The use of urinary growth hormone measurements leads to the classification of more children with disorders of growth having adequate GH secretion than that derived from GH provocati

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01774.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY