Peripheral steroid-gonadotropin interactions and diagnostic significance of double-stimulation tests with luteinizing hormone-releasing hormone in polycystic ovarian disease.
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Biomedical subjects
Publications and source records attributed to J Hammerstein.
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The effects of two consecutive LH-RH injections at 120 min intervals with either a varying first or second LH-RH dose on pituitary gonadotrophin response were investigated in 15 eugonadal women to study pituitary secretory processes. Each volunteer underwent a total of 4 LH-RH double stimulation tests. In group I (n = 8) the first LH-RH dose of each of the 4 tests was fixed at 25 microgram, whereas the second LH-RH dose consisted of either 6, 25, 100 or 400 microgram. In group II (n = 7) the first LH-RH dose varied between 6 and 400 microgram, while the second LH-RH dose was kept constant at 25 microgram. Serum gonadotrophin and serum ovarian steroid levels were determined by radioimmunoassay before and after LH-RH administration. The volunteers in both groups served as their own controls. A linear log-dose response relationship was found between the various doses of LH-RH injected and the corresponding LH and FSH elevations elicited. However, the dose of the first LH-RH injection also significantly influenced the gonadotrophin reaction after the second LH-RH injection in a linear log-dose response relationship. Serum levels of oestradiol, 17-hydroxyprogesterone and progesterone significantly increased in response to the elevated serum gonadotrophin levels after LH-RH stimulation during the 4 h test period, but the rise did not correlate to the LH-RH dose used. The results indicate that LH-releasing hormone stimulates not only the release, but also the synthesis of LH and FSH in a dose-related manner. These findings are consistent with our previously reported concept that the magnitude of LH and FSH response to the first LH-RH injection reflects the "storage capacity", while the increase observed after the second LH-RH injection represents the "synthesis capacity" of the gonadotrophs.
Results of HCG-determinations in human serum and cystfluid of benign mammary tumors are presented. HCG was determined gy RIA in 40 samples from 30 patients with different forms of fibro-cystic mastitis. In 60% of the cases positive results were obtained. It is still unclear, whether the demonstrated substance is native HCG, a free beta-subunit, a mixture of both or a different substance with immunologic properties similar to those of HCG.
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155 patients have been treated with epimestrol during 593 menstrual cycles in a daily dosage of 5, 10 or 2.5 mg from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 patients with secondary amenorrhoea, anovulatory cycles, ovulatory oligomenorrhoea, corpus luteum insufficiency, and normal cycles received epimestrol after an average period of 2.4 years of involuntary infertility. The pregnancy rate was 21% (n = 30), the spontaneous abortion rate 13% (n = 4). Twelve further patients not seeking pregnancy were treated with epimestrol because of secondary amenorrhoea and (or) anovulatory bleeding. The results were as follows: 1) In eugonadotropic secondary amenorrhoea 8 out of 12 patients ovulated, 5 out of 10 patients wanting children became pregnant. No patient with hypogonadotropism ovulated. 2) Out of 25 patients with anovulatory cycles or bleeding 13 ovulated and 4 became pregnant. 3) 17 out of 68 oligomenorrhoeic patients became pregnant. 4) In 12 out of 24 patients with corpus luteum insufficiency the hyperthermic phase improved and four patients became pregnant. 5) In 12 patients without anomalous cycles these remained unchanged and there were no pregnancies. 6) No side effects could be observed.
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The effects of ethinylestradiol (1 mug/kg body weight daily) on plasma renin substrate concentration, other factors of the renin-aldosterone-system, and on the cortisol-binding capacity of transcortin were determined in 8 young men and 9 young women. The absolute and relative elevation of plasma renin substrate after 5, 14, and 24 days of ethinylestradiol administration was significantly (P less than 0.001) greater in females than males. Control and posttreatment transcortin levels were also higher in women than men, but the percentage increase did not differ between males and females. It is likely that sex differences in the response of plasma renin substrate to the estrogen are due to differences in hepatic synthesis and/or release of renin substrate. In females, plasma renin activity, angiotensin II concentration, and urinary aldosterone excretion rose significantly although less markedly than plasma renin substrate concentration, while in males only the increase in plasma angiotensin II concentration was significant. These results indicate that no safe conclusions on metabolic effects of estrogen treatment in women can be drawn from experiments carried out in male subjects.
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In four women with cyclical oedema related to the menstrual cycle, weight, leg volume, urinary excretion of sodium, aldosterone and oestrogens, plasma concentrations of progesterone, angiotensin II and plasma renin activity were measured at intervals during 4 weeks while they were taking a fixed sodium diet. In another patient, regular biphasic changes in weight and basal body temperature, disappearing after ovariectomy, were demonstrated. Changes in weight (varying between 3.5 and 5.5 kg) with corresponding changes in sodium balance were observed. In three patients, the maximum weight occurred in the second half, and in the other patient in the first half of the menstrual cycle. Plasms renin activity was in the normal range in all patients. It tended to rise when weight fell and vice versa. Aldosterone excretion behaved similarly and seems to be related to plasma progesterone in three patients. Orthostatic increase in leg volume did not significantly correlate with change in early morning weight. Thus, renin, aldosterone and orthostatic pooling of plasma fluid did not seem to be of primary importance in the pathogenesis of oedema in these patients. Oestrogen excretion in the luteal phase of the cycle was abnormally low in two patients; both had premenstrual oedema. In none of the patients could sodium retention be explained by excessive oestrogen and/or diminished progesterone production.
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A combined adsorption-gel filtration technique has been developed for the quantitation of the cortisol-binding capacity of transcortin: Endogenous steroids are removed from plasma by adsorption on uncoated charcoal. Saturation of the "stripped" binding sites of transcortin is accomplished by equilibrating the sample with a definite amount of labeled cortisol of low specific activity (0.1 muCi/mug). Transcortin-bound [4-14C]cortisol is isolated by gel filtration over Sephadex G-50 at 4 degrees C and measured by liquid scintillation counting. The cortisol-binding capacity of transcortin is calculated directly on the basis of the known specific activity of cortisol. The modification described eliminates methodological disadvantages associated with the original gel filtration procedures, i.e. the possible interference of various endogenous steroids with cortisol binding to transcortin, and the necessity of fluorometric or colorimetric determination of protein-bound cortisol. The values of the cortisol-binding capacity of transcortin in plasma obteined by this simplified assay are in close agreement with results reported in the literature (mean +/- S.D.): healthy males 261 +/- 23 mug/l) of transcortin-bound cortisol (n = 13), healthy nonpregnant females 255 +/- 31 mug/l (n = 15), and pregnant females prior to delivery 560 +/- 82 mug/l (n = 12).
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