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Search for other papers by E. Davies Jones in
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ABSTRACT
Previous studies have shown that freezing and thawing of human thyroid homogenates releases a water-soluble substance which reversibly binds to TSH-receptor antibodies. This substance has been designated long-acting thyroid stimulator absorbing activity (LAA). We now describe a new method for measuring LAA based on the TSH-receptor assay and application of the technique to the study of LAA.
Our results indicate that LAA is a heat-labile glycoprotein which co-elutes with haemoglobin on gel filtration. Furthermore, LAA is retarded by columns of Sepharose–TSH but not by Sepharose coupled to human chorionic gonadotrophin, normal immunoglobulin G or bovine serum albumin, suggesting that LAA contains a binding site for TSH as well as for TSH-receptor antibodies. It would seem therefore that LAA is a water-soluble fragment of the TSH receptor possibly resulting from proteolytic cleavage of the receptor at a site close to the cell surface.
J. Endocr. (1984) 100, 113–118
Search for other papers by GWYNETH E. JONES in
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Search for other papers by A. R. BOYNS in
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SUMMARY
Intravenous injections of synthetic LH-RH stimulated LH secretion in male dogs. Pretreatment with 50 μg oestradiol-17β, 60 or 165 min but not 15 min before LH-RH, inhibited LH secretion. Injection of 0·1–10 μg oestradiol 165 min before administration of LH-RH, blocked LH secretion. Basal plasma LH levels before LH-RH administration were lower in dogs given oestradiol than in controls.
Search for other papers by GWYNETH E. JONES in
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SUMMARY
Intravenous injections of synthetic luteinizing hormone releasing hormone (LH-RH) stimulated LH secretion in male dogs. An i.m. injection of 0·025–2·5 mg oestradiol-17β given 2·5 h but not 24 h before administration of LH-RH blocked LH secretion. Diethylstilboestrol (2·5 mg) also blocked LH secretion but meso-dihydrodibutylstilboestrol (2·5 mg) was without effect. Testosterone (2·5 and 25 mg), dihydrotestosterone (2·5 mg), 5α-androstane-3α, 17β-diol (2·5 mg), 5α-androstane-3β, 17β-diol (2·5 mg), 5α-androstane-3α, 17α-diol (0·125 mg), 5α-androstane-3β, 17α-diol (0·125 mg) and progesterone (25 and 50 mg) did not prevent LH-RH stimulation of LH secretion.
Search for other papers by E. W. HILLHOUSE in
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Search for other papers by M. T. JONES in
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SUMMARY
The rat hypothalamus in vitro preparation was used to investigate the effect of bilateral adrenalectomy, with and without replacement therapy, on the release of corticotrophin-releasing factor (CRF). Corticotrophin-releasing factor was estimated using 48 h basal hypothalamic lesioned assay rats and corticosterone production of excised adrenals was used as the end point.
Bilateral adrenalectomy resulted in depletion of hypothalamic CRF content within the first 2 h after the operation but this effect was prevented by replacement therapy with corticosterone. Thereafter, the hypothalamic CRF content returned to values not significantly different from the intact control level. Bilateral adrenalectomy caused an increase in both basal and acetylcholine-induced release of CRF and it is suggested that corticosteroids exert a negative feedback effect on the hypothalamus.
Search for other papers by G. IRVING in
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Search for other papers by D. E. JONES in
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Search for other papers by A. KNIFTON in
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SUMMARY
Plasma progesterone concentration was measured by a competitive protein-binding method in serial samples of jugular venous blood from 21 pregnant goats, 11 with twin and 10 with single foetuses.
Progesterone levels in twin pregnancies were significantly greater than in singletons. The mean progesterone concentration (ng/ml plasma) in the twin pregnancies was greatest during the 3rd month of gestation (10·7 ± 0·4 (s.e.m.)) and in the singletons during the 4th month (7·8 ± 0·2 (s.e.m.)). There was a significant decrease in mean progesterone concentration in the last month of pregnancy due to a steady decline in the last 7 days before parturition.
The mean progesterone concentrations at parturition in five twin and eight single pregnancies were 2·2 ± 0·4 and 1·5 ± 0·2 (s.e.m.) ng/ml plasma respectively; there was no significant difference between these values. In cord blood from nine kids immediately after delivery the progesterone concentration was 0·9 ± 0·1 ng/ml.
Search for other papers by H. E. H. JONES in
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Search for other papers by G. S. POPE in
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SUMMARY
1. A method is described for the isolation of miroestrol from Pueraria mirifica in about 50% overall yield.
2. Details of the oestrogenic potency of two derivatives of miroestrol are given.
3. Evidence is presented for the existence of a second, more water-soluble oestrogen in P. mirifica, and preliminary results are given of assays for oestrogen content of various parts of the P. mirifica plant and of other species of Pueraria.
Search for other papers by H. E. H. JONES in
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Search for other papers by G. S. POPE in
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SUMMARY
1. Assay of the potency of the recently isolated plant oestrogen, miroestrol, shows that when given subcutaneously in multiple doses it is as potent as oestradiol-17β, and orally more than three times as potent as stilboestrol in producing an increase in uterine weight in the immature female mouse.
2. In the immature female mouse given a single injection of oestrogens, the route of administration influences the magnitude, the latent period, and the duration of the responses in the reproductive tract. In general, the oestrogens act most efficiently on the uterus and vagina when they are given intraperitoneally instead of subcutaneously. It is suggested that this is because there is less chance of absorption rates and metabolism in the animal influencing the oestrogen introduced intraperitoneally.
3. The activity of miroestrol by single injection is described and compared with that of oestriol, oestradiol-17β and stilboestrol. It is at least as effective as oestradiol-17β and stilboestrol in promoting uterine and vaginal growth, and in increasing the amount of fluid which can be expressed from the uterine lumen by gentle pressing.
Search for other papers by R. F. GLASCOCK in
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Search for other papers by H. E. H. JONES in
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SUMMARY
1. A grass-clover mixture and turnips were grown on control plots and on plots dressed with hexoestrol at rates of 3·7 and 14·8 g/acre; that applied at the lower rate was labelled with tritium.
2. No oestrogenic activity was detected in any of the crop samples taken at intervals over 4 months, indicating that the hexoestrol content was less than the minimum which was detectable: between 10 and 19 μg/kg fresh weight.
3. The specific activities of plant samples from the plots dressed with labelled hexoestrol corresponded to 0·12–0·49 μg hexoestrol/kg fresh weight which is clinically insignificant for the consumer.
4. The presence of an unidentified oestrogen, with marked local variations in concentration, was detected in the soil of the control plots.
5. Bioassay and tritium determinations on soil extracts showed that the method used extracted 20% or less of the applied hexoestrol.
6. During 3 months there was no appreciable change in the specific activity of the soil dressed with labelled hexoestrol, showing that neither hexoestrol nor any possible decomposition products had been lost by evaporation or by leaching.
7. It required 7 days' continuous treatment with ethanol in a soxhlet apparatus before the calculated amount of radioactivity was extracted from soil samples taken at the beginning and end of the experiment, dried by heat and stored for several months. Only 9–11% of the radioactivity in the extracts was in the chemical form of hexoestrol. The significance of this is discussed.
Search for other papers by E. H. D. CAMERON in
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Search for other papers by T. JONES in
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Search for other papers by A. B. M. ANDERSON in
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Search for other papers by K. GRIFFITHS in
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SUMMARY
As part of a continuing study of adrenal steroids in relation to breast cancer, various experiments were performed in order to study relationships between androgen and corticosteroid biosynthesis. Chopped tumour tissue from a 'mixed cell' adrenal adenoma (7·4 g.) removed from a patient in Cardiff Royal Infirmary was incubated with [4-14C]pregnenolone and [7α3H]17α-hydroxypregnenolone for periods of time ranging from 30 to 120 min. The results of this work suggest that 17α-hydroxyprogesterone may not be an obligatory intermediate in androgen or cortisol synthesis. Evidence from further experiments with 'normal' human adrenal tissue removed from breast cancer patients using previously established ultramicrochemical techniques indicates that dehydroepiandrosterone (DHA) sulphokinase enzyme system is confined to the zona reticularis of the gland. The conversion of [7α-3H]DHA sulphate, [7α-3H]androstenedione and [7α-3H]testosterone to oestrogens and their conjugates by adrenal homogenates was also investigated. Conversions were extremely low from all precursors.
Search for other papers by M. T. JONES in
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Search for other papers by E. W. HILLHOUSE in
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Search for other papers by JANET BURDEN in
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SUMMARY
The effect of incubating the hypothalamus of adult male rats with various neurotransmitters upon the release of corticotrophin-releasing hormone (CRH) was studied. The CRH activity in the incubation medium was assayed in 48 h median eminence-lesioned rats and the corticosteroidogenesis of excised adrenals in vitro was used as the end-point. 5-Hydroxytryptamine (100 pg/ml–10 ng/ml) caused a dose-dependent release of CRH which was antagonized by methysergide (30–100 ng/ml). The response to 5-hydroxytryptamine was also inhibited by hexamethonium and atropine which indicated that it was acting through a cholinergic interneurone. Melatonin (10 ng) did not alter the basal release of CRH but inhibited the action of both 5-hydroxytryptamine (10 ng) and acetylcholine (3 pg). Thus it appears that both 5-hydroxytryptamine and melatonin play a role in the control of CRH release. Noradrenaline blocked the release of CRH induced by both acetylcholine and 5-hydroxytryptamine and presumably this inhibition was caused by direct action on the CRH neurone. γ-Aminobutyric acid (GABA) also inhibited the release of CRH and may also be involved in the regulation of CRH secretion. The inhibitory neurotransmitters, noradrenaline, GABA and melatonin, act via independent receptor mechanisms. A model based on the above data is presented.
