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SUMMARY
1. The administration of 17α-hydroxyprogesterone to a patient with congenital adrenal hyperplasia resulted in 12% of the dose being excreted as pregnanetriol, 6% as 17α-hydroxypregnanolone and < 0·2% as androsterone plus aetiocholanolone.
2. It is concluded that in order to account for the large amounts of androsterone and aetiocholanolone excreted by the untreated patient it is necessary to postulate the secretion by the adrenal of large amounts of a C19 precursor of these two steroids.
3. The possible routes for the biosynthesis of this adrenal androgen are discussed.
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SUMMARY
Administration of 17α-ethyl-19-nortestosterone (50–100 mg/day) to four men with peptic ulcers caused a reduction in the excretion of 17-ketosteroids and 17-ketogenic steroids. All the major urinary 17-ketosteroids were decreased by this treatment, but 11β-hydroxyandrosterone appeared to be least affected.
Single injections of androst-4-ene-3:17-dione were given to one patient both before and during the period of ethyl-nortestosterone treatment. Recovery of the metabolites of androstenedione in the 48 hr following injection was virtually the same in the pretreatment and treatment periods. This was interpreted to mean that alteration of the metabolism of this adrenal steroid was not the basis of the suppression of ketosteroid excretion.
It is therefore concluded that 17α-ethyl-19-nortestosterone can cause suppression of adreno-cortical secretion.
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SUMMARY
The steroid excretion of patients with three types of post-pubertal hirsutism has been studied both before and during the administration of corticotrophin. The types of hirsutism distinguished were post-pubertal adrenal virilism (three cases), idiopathic hirsutism (five cases) and the Stein-Leventhal syndrome (seven cases).
1. The patients in the adrenal virilism group were found to have a pattern of steroid excretion of the type seen in congenital adrenal hyperplasia. Thus they excreted relatively small amounts of cortisol metabolites in the urine, but the excretions of pregnanetriol, 17-hydroxypregnanolone, 11-oxopregnanetriol and 11-hydroxyandrosterone were high.
2. The patients with idiopathic hirsutism showed a tendency to excrete relatively more of those 17-oxosteroids derived from C19 precursors compared with those derived from cortisol. The evidence suggests, however, that this disproportion is due not to an impairment of cortisol synthesis but to a potentiation of the production of adrenal androgens.
3. A similar abnormality in the patterns of steroid excretion was also found in some of the patients with the Stein-Leventhal syndrome. Since this abnormality includes the excretion of increased amounts of those 17-oxosteroids thought to be exclusively of adrenal origin, viz. dehydroepiandrosterone and 11-hydroxyandrosterone, this would suggest adrenal involvement in at least some of the cases.
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SUMMARY
1. 17-Ketosteroids (KS) and 17-ketogenic steroids (KG) may be determined in guinea-pig urine by the method of Norymberski, Stubbs & West [1953]. Studies on the fractionation of urinary steroids showed the method was applicable to the urine of pregnant guinea-pigs.
2. So little material in the faeces of guinea-pigs behaved as KS that excretion by this route may be ignored.
3. Daily vaginal lavages shortened the oestrous cycle in the guinea-pig and abolished the peak of KS excretion seen at oestrus in normal cycles. No consistent trend in the excretion of KG was seen during normal oestrous cycles. No cyclical change in KS excretion was seen after ovariectomy.
4. During pregnancy in the guinea-pig, there was a rise in the excretion of KG and KS. The increase was not abolished by ovariectomy. The rise did not occur in one adrenalectomized animal which went to term, though it continued to excrete significant amounts of KS. The contribution of the foetal adrenals to the excretion of steroids by the pregnant mother was probably small.
5. Non-specific adrenal stimulation caused a rise in the urinary excretion of KS and KG.
6. Fractionation of the KS released from the urine of an intact non-pregnant guinea-pig by a mild hydrolytic procedure gave five major compounds, one in the 11-deoxy and four in the 11-oxy fraction. All five compounds were excreted in increased amounts by a pregnant intact and by a pregnant adrenalectomized guinea-pig.
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SUMMARY
Changes in response of the adrenal cortex to corticotrophin caused by the simultaneous intravenous administration of tri-iodothyronine have been studied in two patients with anterior pituitary insufficiency.
Tri-iodothyronine caused increases in urinary excretion of ketogenic steroids and in plasma hydrocortisone. Blood eosinophils fell sharply. In addition, changes in sodium and potassium balance, and fasting blood sugar levels were observed which were consistent with increased activity of the adrenal cortex. Rapid changes in b.m.r., serum creatine and blood cholesterol were those known to be produced by tri-iodothyronine alone; so, to a large extent, was the increased negative nitrogen balance.
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SUMMARY
Ovarian metabolism of C19-steroids and oestrogens has been assessed at ovarian wedge resection in 22 patients with polycystic ovaries. There were marked variations between different patients.
High concentrations of androstenedione were found in ovarian vein plasma in some patients, and always after stimulation with human pituitary follicle-stimulating hormone (HP-FSH) in vivo. Its contribution to the daily production of testosterone has been considered. No measurable amounts of testosterone or dehydroepiandrosterone were found. Oestradiol concentration was sometimes normal or above.
Large amounts of androstenedione were generally isolated from cyst fluid. Occasionally testosterone was found and also epitestosterone after FSH. That concentrations of oestrogens in cyst fluid are low was confirmed, but sometimes higher levels were found after FSH.
Slices of ovarian tissue generally converted progesterone or pregnenolone to androstenedione in high yield but conversion to oestrogen appeared to be low. However, the difficulty of making quantitative comparisons by this method, in the absence of knowledge of the sizes of the pools of endogenous steroids in the tissue, has been recognized.
No evidence was found in any of the 18 cases examined for a lack of 3β-hydroxysteroid dehydrogenase.
In vitro synthesis of epitestosterone by both normal and polycystic ovaries has been observed.
A coincidental granulosa cell tumour in one patient synthesized testosterone in high yield.
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SUMMARY
In this paper the problems of establishing the identity of a compound isolated from biological material with a steroid are outlined and discussed. The nature of evidence required for identification and some techniques for obtaining this are briefly considered. The importance of establishing the specificity of a method for the quantitative measurement of a steroid in a biological extract is emphasized.
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SUMMARY
C19-steroids, testosterone and oestrogen production rates have been measured simultaneously by urinary isotope dilution in a group of 18 patients with polycystic ovaries and in two normal women.
The production of total C19-steroids remained high in seven patients under dexamethasone suppression, suggesting a major ovarian contribution. In eight it did not remain high, suggesting a major adrenal contribution.
The rate of testosterone production was usually normal under dexamethasone. The rate of oestrogen production was not subnormal and even occasionally raised.
Ovarian wedge resection produced a good clinical response in 75% of the observations, and C19-steroid production fell. The latter was not so evident if there was no clinical response. Testosterone production was usually reduced. Oestrogen production rate changed irregularly.
Administration of human pituitary follicle-stimulating hormone caused a concurrent increase in C19-steroids, testosterone and oestrogen production in four out of five patients.
The inadequacy of the urinary isotope dilution technique, in attempting to measure testosterone secretion and interconversion of testosterone and androstenedione in these patients, has been stressed and discussed.
Some correlations have been established with direct observations on ovarian steroid metabolism in certain patients reported elsewhere.
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Search for other papers by G. S. SPATHIS in
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SUMMARY
1. Various parameters of androgen metabolism have been studied in a group of 11 hypogonadal men. They included the rates of: 17-oxosteroid excretion, total production of C-19 steroids, secretion of testosterone and total production of testosterone (including testosterone converted peripherally from other steroids). The concentrations of testosterone and androstenedione were also measured in peripheral and testicular venous plasma. In addition the effects of stimulation and suppression of adrenocortical function and of testicular stimulation were studied.
2. The patients were divided into three groups according to clinical features, gonadotrophin excretion and testicular histology and an attempt was made to correlate these tests with the steroid studies.
3. Patients with poorly developed secondary sexual characteristics had a low testicular secretion of testosterone. There was also an indication that in these cases the adrenal gland contributed significantly to the plasma testosterone.
4. Methods involving estimations of androgens in blood are shown to be of more value than estimations in urine. In some instances anomalous results were obtained for the rates of secretion of testosterone. The possible significance of these anomalies is discussed.
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SUMMARY
A patient is described who showed evidence of 25 years' duration of intermittent hyperadrenocorticalism due to adrenocortical hyperplasia. The most pronounced clinical symptom was oedema formation, which was shown to be associated with phases of increased adrenocortical activity. Cortisol secretion rates, for example, ranged from 24 to 161 mg./24 hr. There was also potassium depletion.
The response to dexamethasone was repeatedly anomalous, there being a tenfold increase in excretion of urinary 17-hydroxycorticosteroids. Responses to metyrapone and pyrogen were absent but the response to insulin appeared excessive. There was no alteration by dexamethasone in vitro of synthesis of cortisol or corticosterone. Binding of plasma cortisol and corticosteroid-binding globulin were decreased.
