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324. Cyclic changes of plasma testosterone in the human male
Abstracts
9B 2. Steroid levels in abnormal conditions-II 323. An assessment of the usefulness of the simultaneous estimation of several individual steroids in blood and urine BROWNING,MARGARETC. K., DOWNIE, W. W., BROWN, ALI~ON and GROVES,MADELEINE,Departments of Clinical Chemistry and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland It has become common practice in diagnostic laboratories to estimate either groups of steroid hormones, e.g. 17-hydroxycorticosteroidsorindividual steroids, e.g. testosterone in biological fluids. Many factors including past or present therapy and concurrent disease states can affect the metabolism of steroid hormones and consequently the results obtained for “group analysis” methods or single individual hormone assays. It is therefore suggested that more valuable information would be obtained if multiple analyses were carried out on single samples and the values obtained for the various hormones correlated. In 1966 Gardiner and Horning described a gas chromatographic method for the fractionation of urinary steroids. This method has been modified and has been used to investigate the alterations in steroid excretion which may occur after the administration of various drugs and also to study the excretion of steroid hormones in cases of hirsutism. Plasma samples have also been analyzed for several steroid hormones and the relative concentrations in various physiological and pathological conditions will be discussed. 324. Cyclic changes of plasma testosterone in the human male DOERING,C. H., KRAEMFX,H. C., BRODIE,H. K. H. and HAMBURG,D. A., Department of Psychiatry, Stanford University School of Medicine, Stanford, California, U.S.A. Our overall interest is in biological substrates of human mood and behaviour. Since testosterone (T), among other steroid hormones, has been associated with behaviour and states of mind, we wanted to assess the lability of circulating T in the human male over a long period of time. Blood samples obtained from 20 healthy young men every second day for 2 months were analyzed for total T concentration by radioligand saturation analysis with late-pregnancy plasma. We found that the fluctuations of T over the total time span were substantial for most individuals; the coefficients of variation ranged from 14 to 42% (median 21%). The presence of periodic functions in these fluctuations was tested by 4 different, relatively independent methods. Close agreement among at least 3, in some cases all 4, analytic methods was found for 12 out of the 20 subjects. These 12 subjects had cycles of plasma T levels with periods ranging between 8-30 days, with a cluster of periods around 20-22 days. The majority of such cycles were significant at least at the 5% level. The amplitudes of these cycles avergaged 17% of the subjects’ mean T levels (range 9-28x).
325. The clinical signikence of measurements of unconjugated-l’lgoestradiol in human urine EDWARDS,R. and JEFFCOATE,S. L., Department of Chemical Pathology, St. Thomas’s Hospital Medical School, London, S.E. 1, England
313
The aim of this study was to measure concentrations of unconjugated oestradiol-17fi (E,) in urine from human subjects and to determine the relationship to the unbound and unconjugated fraction of E, in blood, which is considered to be the biologically active fraction. 1 ml aliquots of urine were extracted with dichloromethane, chromatographed on Sephadex LH-20 (0.5 x 4.5 cm) and assayed for E, using a sensitive and specific radioimmunoassay. The radioimmunoassay used an antiserum raised against an Ez (6 linked)-protein conjugated, antibody coated tubes and ‘**I-histamine-6-E, as tracer. Using this assay unconjugated Ez can be readily measured in urine from normal male and female subjects. An excretion of approximately 100 ng E,/24 h was found for normal males. Levels in normal females were higher and varied throughout the menstrual cycle with midcycle peaks of up to 500 ng E2/ 24 h. Gonadotrophin (Pergonal) administration to both male and female subjects produced increases of urinary unconjugated E,. There was good correlation between blood total E, variations (also measured by RIA) and urine unconjugated E, variations in samples from normal subjects, infertile women during gonadotrophin therapy, stimulation tests with ACTH or FSH and in males with evnaecomastia. The results suggest that measurement of uzonjugated steroid in urine may be a useful indication of circulating biologically active steroid concentrations. 326. Plasma pregnenolone and 17-hydroxypregnenolone in health and disease MCKENNA,T. J., BROWN,R. D. and LIDDLE,G. W., Vanderbilt University School of Medicine, Nashville, Tennessee. U.S.A. To study the physiological and pathological significance of pregnenolone (A 5-P) and 17-hydroxypregnenolone (17A 5-P) precursors common to adrenal and gonadal steroidogenesis, radioimmunoassays for these steroids were developed. Utilizing standard methods of adrenal and gonadal suppression and/or stimulation the following observations were made in normal subjects and in patients with abnormal steroidogenesis. The gonads and adrenals contribute similarly to plasma A 5-P in men and premenopausal women whilst 17-A 5-P is mainly of adrenal origin. In postmenopausal women both steroids are solely of adrenal origin. A diurnal rhythm of 17-A 5-P was noted. Only postmenopausal women and premenopausal women receiving estrogens showed a diurnal rhythm of 45-P. Gonadal A 5-P in men and untreated premenopausal women may have obscured a diurnal variation of adrenal A 5-P. Both steroids were responsive to ACTH and correlated closely with plasma fluorogenic corticosteroids 0, < 0.001). Plasma 17- A 5-P was higher during the follicular than during the luteal phase of the menstrual cycle @ < 0.001); a pattern for A5-P was not seen. A small rise in both steroids was seen following administration of human chorionicgonadotropin. Most patients with adrenal carcinoma had elevated A 5-P or 17- A 5-P. Patients with Cushing’s disease or an adrenal adenoma had normal basal levels of A 5-P and 17- A 5-P, however the normal diurnal rhythm and suppressibility were absent and the corresponding plasma fluorogenic corticosteroids were higher than in normal subjects (suggesting more efficient intra-adrenal utilization of precursors). Basal A 5-P and 17- A 5-P were normal in hirsute women, but 17-A 5-P failed to suppress normally with dexamethasone. In patients with 21-hydroxylase deficiency A 5-P and 17- A 5-P were elevated but fell during treatment with glucocorticosteroids.
9B 2. Steroid levels in abnormal conditions-II 323. An assessment of the usefulness of the simultaneous estimation of several individual steroids in blood and urine BROWNING,MARGARETC. K., DOWNIE, W. W., BROWN, ALI~ON and GROVES,MADELEINE,Departments of Clinical Chemistry and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland It has become common practice in diagnostic laboratories to estimate either groups of steroid hormones, e.g. 17-hydroxycorticosteroidsorindividual steroids, e.g. testosterone in biological fluids. Many factors including past or present therapy and concurrent disease states can affect the metabolism of steroid hormones and consequently the results obtained for “group analysis” methods or single individual hormone assays. It is therefore suggested that more valuable information would be obtained if multiple analyses were carried out on single samples and the values obtained for the various hormones correlated. In 1966 Gardiner and Horning described a gas chromatographic method for the fractionation of urinary steroids. This method has been modified and has been used to investigate the alterations in steroid excretion which may occur after the administration of various drugs and also to study the excretion of steroid hormones in cases of hirsutism. Plasma samples have also been analyzed for several steroid hormones and the relative concentrations in various physiological and pathological conditions will be discussed. 324. Cyclic changes of plasma testosterone in the human male DOERING,C. H., KRAEMFX,H. C., BRODIE,H. K. H. and HAMBURG,D. A., Department of Psychiatry, Stanford University School of Medicine, Stanford, California, U.S.A. Our overall interest is in biological substrates of human mood and behaviour. Since testosterone (T), among other steroid hormones, has been associated with behaviour and states of mind, we wanted to assess the lability of circulating T in the human male over a long period of time. Blood samples obtained from 20 healthy young men every second day for 2 months were analyzed for total T concentration by radioligand saturation analysis with late-pregnancy plasma. We found that the fluctuations of T over the total time span were substantial for most individuals; the coefficients of variation ranged from 14 to 42% (median 21%). The presence of periodic functions in these fluctuations was tested by 4 different, relatively independent methods. Close agreement among at least 3, in some cases all 4, analytic methods was found for 12 out of the 20 subjects. These 12 subjects had cycles of plasma T levels with periods ranging between 8-30 days, with a cluster of periods around 20-22 days. The majority of such cycles were significant at least at the 5% level. The amplitudes of these cycles avergaged 17% of the subjects’ mean T levels (range 9-28x).
325. The clinical signikence of measurements of unconjugated-l’lgoestradiol in human urine EDWARDS,R. and JEFFCOATE,S. L., Department of Chemical Pathology, St. Thomas’s Hospital Medical School, London, S.E. 1, England
313
The aim of this study was to measure concentrations of unconjugated oestradiol-17fi (E,) in urine from human subjects and to determine the relationship to the unbound and unconjugated fraction of E, in blood, which is considered to be the biologically active fraction. 1 ml aliquots of urine were extracted with dichloromethane, chromatographed on Sephadex LH-20 (0.5 x 4.5 cm) and assayed for E, using a sensitive and specific radioimmunoassay. The radioimmunoassay used an antiserum raised against an Ez (6 linked)-protein conjugated, antibody coated tubes and ‘**I-histamine-6-E, as tracer. Using this assay unconjugated Ez can be readily measured in urine from normal male and female subjects. An excretion of approximately 100 ng E,/24 h was found for normal males. Levels in normal females were higher and varied throughout the menstrual cycle with midcycle peaks of up to 500 ng E2/ 24 h. Gonadotrophin (Pergonal) administration to both male and female subjects produced increases of urinary unconjugated E,. There was good correlation between blood total E, variations (also measured by RIA) and urine unconjugated E, variations in samples from normal subjects, infertile women during gonadotrophin therapy, stimulation tests with ACTH or FSH and in males with evnaecomastia. The results suggest that measurement of uzonjugated steroid in urine may be a useful indication of circulating biologically active steroid concentrations. 326. Plasma pregnenolone and 17-hydroxypregnenolone in health and disease MCKENNA,T. J., BROWN,R. D. and LIDDLE,G. W., Vanderbilt University School of Medicine, Nashville, Tennessee. U.S.A. To study the physiological and pathological significance of pregnenolone (A 5-P) and 17-hydroxypregnenolone (17A 5-P) precursors common to adrenal and gonadal steroidogenesis, radioimmunoassays for these steroids were developed. Utilizing standard methods of adrenal and gonadal suppression and/or stimulation the following observations were made in normal subjects and in patients with abnormal steroidogenesis. The gonads and adrenals contribute similarly to plasma A 5-P in men and premenopausal women whilst 17-A 5-P is mainly of adrenal origin. In postmenopausal women both steroids are solely of adrenal origin. A diurnal rhythm of 17-A 5-P was noted. Only postmenopausal women and premenopausal women receiving estrogens showed a diurnal rhythm of 45-P. Gonadal A 5-P in men and untreated premenopausal women may have obscured a diurnal variation of adrenal A 5-P. Both steroids were responsive to ACTH and correlated closely with plasma fluorogenic corticosteroids 0, < 0.001). Plasma 17- A 5-P was higher during the follicular than during the luteal phase of the menstrual cycle @ < 0.001); a pattern for A5-P was not seen. A small rise in both steroids was seen following administration of human chorionicgonadotropin. Most patients with adrenal carcinoma had elevated A 5-P or 17- A 5-P. Patients with Cushing’s disease or an adrenal adenoma had normal basal levels of A 5-P and 17- A 5-P, however the normal diurnal rhythm and suppressibility were absent and the corresponding plasma fluorogenic corticosteroids were higher than in normal subjects (suggesting more efficient intra-adrenal utilization of precursors). Basal A 5-P and 17- A 5-P were normal in hirsute women, but 17-A 5-P failed to suppress normally with dexamethasone. In patients with 21-hydroxylase deficiency A 5-P and 17- A 5-P were elevated but fell during treatment with glucocorticosteroids.