Relationship between saturation of LH receptors and steroidogenic response in isolated rat granulosa cells.
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Biomedical subjects
Publications and source records attributed to P Doerr.
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The 24-h sleep-wake pattern of plasma LH was studied in 18 patients with severe weight loss. Sixteen patients had anorexia nervosa, one suffered from schizophrenia and one had a gastric ulcer. The age of the patients ranged from 13 to 31 years. Seventeen women and one boy participated in the study. Their weight ranged from 51 to 73% of the ideal body weight (IBW) at the first 24-h study which was at one week after admission to the hospital. Blood was taken through an indwelling venous catheter every 30 min. The patients' weight increased under behavioural therapy and they were re-studied when they had gained approximately 10% IBW and again prior to release from the psychiatric ward. The LH patterns were classified as infantile, pubertal or adult. All patients except for two had an infantile pattern at the first study. Except for the two patients who had no anorexia nervosa, all developed a pubertal and/or an adult pattern. All patients whose weight was below 69% IBW had an infantile LH pattern. All patients whose weight was below 69% IBW had an infantile LH pattern. Adult patterns were only seen when the body weight was greater than 80% IBW. The increase of the average 24-h LH values was slower the older the patients were and the longer they had been anorectic.
Sleep disturbances, which are a prominent symptom of depressive illness, were analyzed in endogenously depressed patients during depression and during full remission. These disturbances may be described at the level of sleep stages, at the level of the sleep profile, and at the level of consecutive sleep records. The scoring of sleep stages in sleep records of depressive patients provides difficulties, because the temporal coherence of different electrophysiological descriptors of sleep is weakened during depression. The sleep profile of depressed patients is characterized by alterations in the normal sequence of sleep stages and frequent stage changes. The disturbances in the sleep profile are unstable in that they show marked day to day fluctuations. It could be shown in some patients that there is a correlation between parameters of the first REM sleep and urinary free cortisol excretion in corresponding nights.
Radioimmunoassays for the measurement of pregnenolone, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEA) and androstenediol (5-androstene-3beta, 17beta-diol) have been developed. In addition the reliability criteria of these methods have been established. Age dependence of testosterone precursors in plasma was studied in 80 normal males aged 19 to 93 years. When a young to middle aged group (19-54 years) was compared with an old age group (67-93 years) a highly significant (P less than 0.001) decrease was observed for all the precursors studied: DHEA -68.1%, pregnenolone -60.3%, androstenediol -53.8%, 17alpha-hydroxyprogesterone -47.5% and androstenedione -39.2%.
Plasma estrone, dihydrotestosterone, luteinizing hormone (LH), and percentage-free testosterone levels were determined in 26 predominantly or exclusively homosexual males (20 to 33 years of age) and in an age-matched control group. Although the homosexual and control groups showed a broad overlapping for all hormonal factors measured, highly significant differences between the groups were found without exception. The medians of the homosexual group (control group) and the significance levels for the two-sample rank tests were as follows: estrone 3.07 (2.43) ng/100 ml, P less than .01; dihydrotestosterone 66.0 (49.2) ng/100 ml, P less than .01; percentage-free testosterone 10.7% (9.7%), P less than .02; LH 35.1 (24.9) ng/ml, P less than .001. These findings can in part be explained by the higher LH secretion in the homosexual subjects.
The response of plasma testosterone, LH and FSH to oral administration of cortisol or dexamethasone was studied for 26 h in 6 groups of 12 normal adult males. Twenty-four hour treatment with cortisol (60 mg at 1000 h, followed by 30 mg at 2 h intervals) or with dexamethasone (6 mg at 1000 h, followed by 3 mg at 6 h intervals) was without effect on testosterone during the day but suppressed the nocturnal rise completely. LH and FSH did not decrease at any time during the day and showed a highly significant increase during the second part of the night. Short-term treatment (1000-1600 h, 1600-2200 h or 2400 h-0800 h) with cortisol was less effective in suppressing the nocturnal rise in testosterone. It was concluded that administration of cortisol leading to plasma levels as seen under treatment with ACTH suppresses testosterone by abolishing or flattening the nocturnal rise. This effect was not mediated by changes in LH or FSH. Our data suggest that the ACTH-induced suppression of testosterone is due to an action of cortisol.
A radioimmunoassay (RIA) for oestrone (Oe1) in plasma was developed using an ether extraction, a partition between NaOH and light petroleum, and a TLC as sample purification and an antiserum cross-reacting with Oe2 for the final assay (Method A1). The reliability criteria are given in detail. In order to simplify this method a highly specific antiserum was developed by using Oe1-3-hemisuccinate-BSA as an antigen. Using this antiserum for the final assay but omitting the TLC (Method B) the Oe1 concentration in male plasma was 76% overestimated (Method B compared with Method A1). In pregnancy plasma Oe1 could specifically be determined after a simple ether extraction (Method C). It was concluded that the use of a highly specific antiserum (as determined by cross-reaction studies) for the final assay does not necessarily imply that a chromatographic sample purification can be omitted without loss in assay specificity. This appears to be true mainly in cases where the steroid concentration of the sample is low. Normal values of Oe1 from 80 healthy adult males were ascertained by Method A1. Age group I (22-61 years, n = 48) ranged from 1.22-5.60 ng/100 ml, median 2.81; age group II (67-90 years, n = 32) from 1.55-6.40, 100 median 3.41. The small increase of Oe1 with age was highly significant.
A radioimmunoassay for dihydrotestosterone (DHT) in plasma was developed using an antiserum raised against testosterone-3-oxime-bovine-serum-albumin. After extraction of 1 ml male plasma with diethylether, DHT was separated from testosterone (T) by thin-layer chromatography. A dextran-charcoal-suspension was used for the separation of bound and free ligand. The inter-assay variability was 10.4 percent (C.V.) and the detection limit 1.77 ng/100 ml. The accuracy of the method as determined by mass recoveries and the specificity were shown to be satisfactory. Normal values were obtained in 45 young to middle-aged (22-61 years) and 37 old (68-93 years) men. The median and the 95 percentiles were 20.5-51.9-76.3 (ng/100 ml) and 19.5-50.9-101.5 (ng/100 ml) respectively. While DHT did not change in old age T fell by 20.6 percent. DHT and T showed a significant correlation: rS = 0.426, P smaller than 0.01 (young men), rS = 0.752, P smaller than 0.001 (old men). After 3 daily im injections of 5000 IU human chorionic gonadotrophin (HCG), DHT increased 1.50 times (range: 1.15-2.09, n = 12), T 1.86 times (range: 1.20-2.91, n = 12). After 4 daily administrations of 40 mg fluoxymesterone DHT fell to 29.6 percent of the control level (range: 16.0-48.2 percent, n = 12). Blood samples were obtained from a 24 year old man every 15 min for 24 h. A close parallelism was observed between the concentrations of DHT and T in the plasma.
The age related changes on free plasma testosterone (T), dihydrotestosterone (DHT) and oestradiol (OE2) were determined in 82 healthy adult males. Forty-six subjects were between 22 and 61 years of age (group I), 36 between 67 and 93 years (group II). The percentage of free, non protein bound hormone was determined by equilibrium dialysis of undiluted plasma against isotonic phosphate buffer at 37 degrees C. Total hormone concentrations were measured by radioimmunoassay. The percentage of free T was 2.24% (median), 1.65-3.42 (95 percentiles) in group I and 1.65% (1.24-2.26) in group II. The percentage of free DHT decreased from 1.17% (0.80-2.03) in group I to 0.83% (0.52-1.55) in group II. The decrease in % free Oe2 was only very small: group I = 2.49% (2.13-2.96), ad group II = 2.31% (1.95-3.17). The fall in free T by 43.3% from 12.2 ng/100 ml (6.74-25.0) in group I to 6.90 ng/ml (3.57-10.6) in group II was twice as high as that of total T, which decreased on an average by 20.6%. Free DHT decreased by 25.8%: group I = 578 pg/100 ml (266-987), group II =429 pg/100 ml (168-723), while total DHT was not significantly different between the two groups (-1.9%). Free Oe2 was increased in old age: group I = 42.4 PG/100 ML (26.0-69.4), GROUP II = 55.7 PG/100 ML (35.8-118.9). The increase in free Oe2 by 31.4% was almost as high as that of the total Oe2 (46.9%).
The response of plasma oestradiol (Oe-2), oestrone (Oe-1), testosterone (T) and cortisol to dexamethasone and ACTH administration in normal adult males was ascertained. After an oral dose of 1.5 mg dexamethasone Oe-1 decreased from 2. 51 to 1.85 ng/100 ml (74% of the control level, mean of 15 subjects) over night and after continuing the dexamethasone administration for two more days (twice daily 1.5 mg) Oe-1 decreased to 1.30 ng/100 ml (52%). Oe-2 (control level 1.71 ng/100 ml) and T (678 ng/100 ml) did not change over night, but at the end of the test Oe-2 decreased to 84% and T to 91% of the control level. After a single im injection of 2 mg beta 1-24 cortrophin Oe-1 increased 1.9 times (meanof 13 subjects) without further increase during two more days of treatment (twice daily 1 mg), while Oe-2 did not change over night and decreased to 75% of the control level at the end of the test. Under ACTH T decreased to 66% of the control level over night and to 50% at the end of the test indicating a suppression of the testicular hormone secretion. From these results and those reported previously it was concluded that the testicular hormone secretion influences mainly Oe-2 in peripheral plasma, while Oe-1 depends mainly on the adrenal hormone secretion.
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