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In some fields of steroid endocrinology, it has long been accepted that the potency of a hormone may depend not only on its secretion rate and rate of hepatic clearance but also on specific metabolic transformation at the site of the target cell. The crucial role of tissue 5α reductase activity on the action of testosterone is a spectacular example (Peterson, ImperatoMcGinley, Gautier & Sturla, 1977). Curiously—it is easy to be wise after the event—this line of thought seems rarely to have been exercized in explanations of corticosteroid action. Clearly, the severity of diseases of corticosteroid excess, of which Cushing's and Conn's syndromes are the best known examples, is strongly correlated with the secretion rate of cortisol and aldosterone respectively. However, in some forms of hypertension where deranged corticosteroid action might be expected to provide an acceptable explanation (e.g. increased mineralocorticoid secretion in low-renin essential hypertension), no abnormalities of secretion
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Dopamine is capable of modulating zona glomerulosa function. Of this there now seems little doubt. However, whether varying dopamine levels in vivo forms the basis of a realistic normal physiological control mechanism for aldosterone secretion is far from clear. Reviewers have been cautious (Ganguly, 1984) or enthusiastic (Sowers, 1984) depending on the choice of evidence and the weight given to individual studies, but some resolution of the uncertainty is pressing since aberrations in this as yet unproven relationship have been suggested as basic abnormalities in a number of forms of hypertensive disease.
Evidence for and against the dopamine–aldosterone relationship has been obtained using dopamine itself and antagonists or agonists of its action in whole animals and in tissue preparations. Initial impetus for the dopamine hypothesis came from the observation that the dopamine agonist, bromocriptine, inhibited the response of aldosterone to frusemide-induced sodium loss (Edwards, Thorner, Miall et al. 1975) although
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SUMMARY
A method of estimating the peripheral plasma concentration of 11-deoxycorticosterone (DOC) in man by means of gas-liquid chromatography with electron capture detection is described. Purification requirements for samples and chromatographic media have been simplified by the use of a detector bypass valve which reduces the risk of detector contamination. For this reason the method is relatively short. There was no measurable blank using either plasma from an adrenalectomized subject or water. The normal range was found to lie between 4·1 and 17·2 ng/100 ml (mean 9·8). Dexamethasone administration to one subject resulted in a subnormal plasma DOC concentration.
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SUMMARY
1. A method is described of measuring the early thyroid 'clearance' by the technique of Berson, Yalow, Sorrentino & Roswit [1952], with the results expressed as the percentage of extracellular fluid cleared per half hour. This measurement has satisfactorily segregated from a normal group: 10 out of 10 definitely and 11 out of 11 probably thyrotoxic, 11 out of 12 definitely myxoedematous and 1 out of 4 probably myxoedematous patients. The technique is relatively simple and rapid.
2. Measurement of the early thyroid clearance is closely correlated with the urinary 'T' index of thyroid uptake (for log values of each, r=0·90).
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Search for other papers by H M Fraser in
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Pituitary testicular function in the neonate
The early postnatal period of male primates (including humans) is associated with activation of the hypothalamicpituitary-testicular axis. Circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) begin to rise in male infants during the second week of postnatal life, reach a peak between 2 and 4 months, and decline thereafter, reaching juvenile levels by 1 year of age (Forest 1990) (Fig. 1). Total testosterone levels rise commensurate with the increase in neonatal LH, reaching peak values that approach the low normal adult male range between 1 and 3 months of age, and then fall in concert with declining LH values to juvenile levels by 6 to 8 months of age (Forest 1990). Comparable patterns of neonatal endocrine changes have been reported in the chimpanzee, rhesus monkey, cynomolgus monkey, mangabey and marmoset (Steiner & Bremner 1981, Fuller et al. 1982, Mann et al. 1983,
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ABSTRACT
The refractoriness of guinea-pigs to the growth-promoting actions of exogenous GH has been suggested to be due to a deficiency or defect in tissue GH receptors or in GH-receptor gene expression. GH-receptor mRNA was, however, demonstrated by Northern blot analysis and by the polymerase chain reaction in extracts of guinea-pig liver, adipose tissue, brain, hypothalamus and pituitary gland. High-affinity, low-capacity binding sites for radio-labelled ovine GH were also demonstrated on the plasma membranes of guinea-pig liver and were similar to those in rat liver. These results demonstrate that the unresponsiveness of guinea-pigs to exogenous GH is not due to the absence of GH receptors.
Journal of Endocrinology (1992) 133, 357–362
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'... by analogy to the situation with calcitonin, it appears worthwhile to look for PTH in the brain and for physiological and behavioral effects of the hormone in the central nervous system' (Gennari, 1988)
Introduction
Parathyroid hormone (PTH)-like peptides, mRNA and degradative enzymes are present in hypophysiotropic regions of the hypothalamus, in which PTHbinding sites are located on neural membranes. Since exogenous PTH stimulates hypothalamic dopamine metabolism and the release of pituitary prolactin, PTH-like peptides in the hypothalamus may have neuroendocrine roles in the regulation of pituitary function. However, as PTH is produced peripherally and neurological disorders are symptomatic of hyperparathyroid disease states, parathyroidal PTH may also participate in the neuroendocrine control of the hypothalamo-pituitary axis.
PTH in the hypothalamo-pituitary axis
Unlike other peptides of the 'diffuse neuroendocrine system', PTH production was believed to be solely by the parathyroid gland (Rosenblatt et al. 1989), from which PTH
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Cancers of the breast, endometrium and ovary can display endocrine sensitivity—and a proportion of such tumours regress when deprived of hormones (Hawkins & Miller, 1988). As a consequence, endocrine deprivation therapy is a major treatment modality, particularly in patients with breast cancer (Miller, 1990).
Given that endocrine factors also play a critical role in the aetiology of certain tumours (Preston-Martin, Pike, Ross et al. 1990), hormone manipulation might also prevent cancer. Initiatives attempting hormone-prevention of cancer have been given impetus by the availability of relatively non-toxic drugs such as luteinizing hormone-releasing hormone (LHRH) agonists and antioestrogens which block hormone action without the morbidity and irreversibility of surgical and radiological procedures. In this commentary we evaluate current thinking behind the use of hormone suppressant drugs as a method of prevention of cancer and conclude that such an approach is feasible but, in parallel with steroid contraception, there are important long-term consequences
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SUMMARY
A double isotope derivative assay technique for the simultaneous estimation of aldosterone, corticosterone and cortisol in human peripheral plasma is described. With this method, concentrations of the corticosteroids in plasma from adrenalectomized subjects were not significantly different from zero. Further evidence of specificity for aldosterone was obtained by measuring the disappearance rate of a single intravenous injection of unlabelled aldosterone from peripheral plasma, by demonstrating a rapid rise in aldosterone concentration in normal subjects acutely depleted of sodium, and by a comparison of aldosterone levels in patients with primary aldosteronism before and after surgical treatment. A study has also been made of the variation of the ratio of cortisol to corticosterone in normal subjects and of the effect upon this ratio of corticotrophin administration and haemorrhage.
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SUMMARY
A method for determining the plasma concentrations of six major corticosteroids, aldosterone, 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), corticosterone, deoxycorticosterone (DOC), cortisol and 11-deoxycortisol using gas–liquid chromatography with electron capture detection is described. Esterification of suitable derivatives of these compounds with heptafluorobutyric anhydride (HFB) allowed detection of quantities of steroid, ranging from 0·3 pg for androstenetrione HFB (from cortisol) to 2·3 pg for corticosterone HFB. No detectable reagent blank was obtained for any compound when water was used instead of plasma and this was also the case when plasma from an adrenalectomized subject was analysed, with the exception of 18-OH-DOC where a reproducible but negligibly small blank occurred. Coefficients of variation for replicate determinations ranged from 8% for corticosterone to 17% for aldosterone. Concentrations in a series of normal human plasma samples were as follows: aldosterone, 4·0–18·0 ng/ 100 ml; 18-OH-DOC, 20–160 ng/ml; corticosterone, 0·08–0·80 μg/100 ml; DOC, 2·8–16·0 ng/100 ml; cortisol, 2·5–10·0 μg/100 ml;and 11-deoxycortisol, 40·0–400·0 ng/100 ml. When seven normal subjects were treated with dexamethasone, concentrations of DOC, cortisol and 11-deoxycortisol fell to below the limit of the normal range, those of 18-OH-DOC and corticosterone were at the lower end of the normal range while the concentration of aldosterone was not significantly affected.
