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Search for other papers by L. J. DONALDSON in
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Search for other papers by G. H. THOMAS in
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SUMMARY
DNA synthetic activity was monitored in rat and human prostate using [125I]iododeoxyuridine ([125I]UdR). Fresh prostate tissue from 6-week-old rats showed higher incorporation of [125I]UdR than that from 12- or 26-week-old rats. During culture for up to 6 days in the absence of hormones, the incorporation of [125I]UdR fell to a low level for all three age groups. Stimulatory effects were seen when rat prostates were cultured in the presence of insulin (3 μg/ml) and testosterone (10−7 mol/l), the incorporation on day 4 of culture being commensurate with that of fresh prostate of the corresponding age. Thus the magnitude of the response was higher for the 6-week-old prostate than that for the other two age groups. A similar age-related pattern of androgen stimulation was observed in experiments in which immature and adult castrated rats were injected daily with testosterone and the freshly removed prostates were incubated with [125I]UdR.
Although insulin, by itself, had a stimulatory effect on [125I]UdR incorporation in cultured prostate, the magnitude of the response did not differ in the 6- and 26-week-old prostate tissue. Maximal stimulation was obtained using 25 μg insulin/ml.
Tissue from a benign prostatic hyperplasia was also responsive to insulin in culture but it differed from rat prostate in that increased proliferative activity occurred even in the absence of hormone stimulation. This spontaneous surge in activity during culture tended to mask the stimulatory effects of insulin and testosterone at concentrations of 3 μg/ml and 10−7 mol/l respectively.
Search for other papers by SUSAN L. RUSSELL in
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Search for other papers by G. H. THOMAS in
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SUMMARY
The metabolism and uptake of [2,4,6,7-3H]oestrone and [2,4,6,7-3H]oestradiol-17β were examined in explants of rabbit uterus, vagina and skeletal muscle in organ culture for 1 and 3 days. Irrespective of whether the uterus was cultured in the presence of [3H]oestrone or [3H]oestradiol-17β, the tissue contained predominantly [3H]oestradiol-17β. This was also true for vagina, but muscle showed only a limited ability to interconvert the two oestrogens.
The oestradiol-17β binding capacity of cultured uterus was also determined, and was shown to decline rapidly over the first 24 h of culture.
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Search for other papers by L Thomas in
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Search for other papers by CL Adam in
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Circulating concentrations of leptin in sheep correlate with body fatness and are affected by level of food intake and photoperiod. The present objective was to elucidate the short-term dynamics of leptin secretion. Frequent blood samples were taken over 48 h from 12 Soay rams after 16 weeks in short-day photoperiod (SD, 16 h darkness:8 h light) with freely available food, and then after 16 weeks in long days (16 h light:8 h darkness) with food freely available (LD) or restricted to 90% maintenance (LDR) (n=6/group). During the second 24 h of sampling, half were food deprived (n=6, SD and LD) and half had their meal times shifted (n=6, SD and LDR). A homologous RIA was developed, using antibodies raised in chicken against recombinant ovine leptin, to measure plasma concentrations. Simultaneous 24 h profiles of plasma insulin, glucose and non-esterified fatty acids (NEFA) were measured. Plasma leptin was higher in LD than SD, and in LD than LDR, associated with higher food intake, liveweight and body condition score (adiposity), but tended to be lower in LDR than SD, associated with lower food intake, liveweight and body condition score. There was no evidence for a circadian rhythm of plasma leptin, but clear evidence for post-prandial peaks of low amplitude (15-36%) 2-8 h after meals given at normal and shifted times. Complete food deprivation caused a dramatic fall in plasma leptin to basal levels within 24 h. There was a positive association of plasma leptin with plasma insulin, and negative association with NEFA, both between meals and during fasting. Thus, plasma leptin concentrations in sheep are sensitive to short-term changes in energy balance, as well as to long-term photoperiod-driven changes in food intake and adiposity.
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Search for other papers by W. G. Thomas in
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ABSTRACT
Recent evidence suggests that angiotensin II (AII) acts on the liver via specific receptors. The aims of this study were to examine the general binding properties of these receptors in the rat and to determine the role of dietary Na+ and AII in the regulation of AII receptors.
Binding of 125I-labelled Ile5-AII to liver membranes was saturable and behaved as a single class of sites with an affinity (K a) of 2·9 l/nmol and a Hill coefficient of 0·99. Kinetic analysis of AII binding gave estimates for the rates of association and dissociation of 42 l/μmol per min and 1·5 × 10−2/min respectively. The binding of analogues exhibited the following order of potency: Val5-AII > Ile5-AII > AIII > Sar1-Ala8-AII > Sar1-Gly8-AII > AI > des-Asp-AI > C4−C8 pentapeptide > Phe1-Tyr8-AII > neurotensin > luteinizing hormone-releasing hormone. Binding was enhanced by Mg2+ and Ca2+ and inhibited by EDTA and the reducing agent dithiothreitol. Low dietary Na+ affected in a biphasic manner both the K a and concentration (R o) of liver AII receptors. Initially, R o decreased from 25·9±3·8 (control) to 16±1·9 (s.e.m.) pmol/g tissue by 1·5 days but thereafter it rapidly increased to 47·3±8·7 pmol/g tissue (3·5 days) and remained elevated to the end of the experiment, 8·5 days later. The K a initially increased from 2·7±0·3 (control) to 4·3±0·5 l/nmol (1·5 days) and then decreased steadily to 1·2±0·1 l/mol (8·5 days). The effect of AII was examined by infusing 24 pmol AII/kg per min for 5 days into the jugular vein by subcutaneous osmotic minipumps. The response was qualitatively similar to that for low dietary Na +. It was concluded that the rat liver has a high content of specific AII receptors that are responsive to changes in Na+ and AII.
J. Endocr. (1985) 106, 103–111
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Search for other papers by MARGARET ABEL in
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Search for other papers by P. W. NATHANIELSZ in
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It is now well established that several hormones are secreted in an episodic or pulsatile fashion (McNatty, Cashmore & Young, 1972; Murray & Corker, 1973). When plasma concentrations of certain hormones are examined, peaks occur at intervals related to different features of the 24-h cycle, circadian rhythms (Retiene, Zimmerman, Schindler, Neuenschwander & Lipscomb, 1968). Circadian and episodic patterns in thyroid function have been claimed by certain workers (Bakke & Lawrence, 1965; Blum, Greenspan & Magnum, 1968) and refuted by others (Schatz & Volpe, 1959; Odell, Wilber & Utiger, 1967). A partial explanation of these conflicting results probably lies in functional differences in the level of the hypothalamo-pituitary-thyroidal-peripheral target tissue axis under investigation by different techniques.
Five Jersey bull calves aged between 2 and 80 days were investigated on a total of nine occasions. Five experiments were conducted under natural lighting conditions (daylight from 04.30 to 19.30 h). Calves in the
Search for other papers by R. D. BULBROOK in
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Search for other papers by B. S. THOMAS in
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Search for other papers by B. W. L. BROOKSBANK in
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SUMMARY
1. There is a very high correlation between the amounts of urinary androstenol and those of dehydroepiandrosterone, androsterone and aetiocholanolone in women with metastatic breast cancer.
2. In spite of this correlation, which implies a common precursor, tritiated dehydroepiandrosterone or testosterone are not metabolized to androstenol at the periphery (maximum conversion: 0·4% of injected dose) in amounts sufficient to account for the urinary androstenol.
3. As a means of evaluating 'androgen status' androstenol assays do not appear to be more useful than those of the 11-deoxy-17-oxosteroids.
Search for other papers by G. B. Thomas in
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ABSTRACT
Hypothalamic control of prolactin secretion was studied in ovariectomized ewes by comparing the effects of hypothalamo-pituitary disconnection (HPD) and sham-operation (sham-HPD). HPD caused a two-fold increase in plasma prolactin concentrations on days 1 and 7 following surgery during anoestrus and a tenfold increase during the breeding season. Thereafter, concentrations gradually declined to be similar to those in sham-HPD ewes by day 43 (breeding season) and day 145 (anoestrus). The maximum plasma prolactin response to HPD was similar during the two seasons (anoestrus: 128 ± 15 vs breeding season: 118 ± 13 μg/l). Sham-HPD had no effect on plasma prolactin concentrations. Prolactin pulse frequency was not affected by HPD, but increases in plasma prolactin concentrations were associated with increases in pulse amplitude. At the time of the normal anoestrus, plasma prolactin concentrations rose in both the HPD and sham-HPD ewes, raising the question of extra-hypothalamic regulation of seasonal changes in prolactin secretion. Plasma LH and FSH concentrations became undetectable in HPD ewes but were unaltered in sham-HPD ewes. We conclude that hypothalamic inhibition of pituitary prolactin secretion in the sheep can be demonstrated by HPD but that this effect is not sustained. This transience may indicate the additional requirement of hypothalamic-releasing factors in the control of prolactin release. In addition, the surgically isolated ovine pituitary of the HPD animal has an inherent pulsatile secretion of prolactin.
J. Endocr. (1986) 111, 425–431
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Search for other papers by G B Thomas in
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Search for other papers by L G Moore in
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Search for other papers by I J Clarke in
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Abstract
The putative negative feedback effects of IGF-I and IGF-II on GH secretion were tested by intracerebroventricular (icv) and intrapituitary administration to sheep. Over two consecutive days, serial jugular blood samples were taken at 10 min intervals for 6 h from ewes (n=3/group) fitted with indwelling stainless steel cannulae into the lateral or third cerebral ventricles. The sheep were injected (icv) with either vehicle or purified ovine IGF-I (2, 4 or 8 μg). IGF-I injection had no effect on plasma GH secretion. Serial blood samples were taken from a second group of nine ewes in which ovine or recombinant human (rh) IGF-I was infused (2·5 μg/h for 2 h) into the third ventricle; once again, IGF-I failed to affect the episodic pattern of GH secretion. Three ewes fitted with indwelling stainless steel cannulae placed in the anterior pituitary gland were consecutively infused with either ovine or rhIGF-I (2·5 μg/h for 2 h) or vehicle. Plasma GH concentrations were suppressed in 3/3 sheep from 1–1·5 h after the commencement of infusion and GH levels remained low for the remainder of the sampling period. In another group of five ewes synergistic effects of IGF-I and IGF-II on GH secretion were tested by icv infusion of rhIGF-I, rhIGF-II, or rhIGF-I+rhIGF-II (5 μg/h for 2 h) or vehicle (sterile 10 mm HCl/saline). Each sheep received each treatment in a randomised design. Infusion (icv) of IGF-I and IGF-II alone or in combination failed to alter GH secretion.
These observations suggest that IGF-I derived from peripheral tissues may modulate GH release at the pituitary level but that IGF-I acts neither alone nor in conjunction with IGF-II as a negative feedback regulator of GH secretion via the hypothalamus in the ewe.
Journal of Endocrinology (1995) 144, 323–331
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Search for other papers by MARIAN SILVER in
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Search for other papers by A. L. THOMAS in
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SUMMARY
Foetal plasma thyroxine levels as well as thyroxine turnover and placental permeability to this hormone were investigated in the conscious pregnant ewe with foetal and maternal intravascular catheters. Foetal plasma thyroxine levels ranged from 4·6 to 6·2 μg/100 ml between 103 days of gestation and the day of birth. Maternal plasma thyroxine levels varied between 2·3 and 4·1 μg/100 ml over the same period. The maternal: foetal ratio across the placenta for thyroxine varied from 0·52 to 0·65. Distribution of radioactive thyroxine injected into the foetal or maternal circulation demonstrated the impermeability of the placenta to thyroxine. Maternal to foetal ratios for labelled thyroxine were 6·2 to 11·9 when injected into the maternal circulation and 0·013 to 0·003 when injected into the foetal circulation. The sheep placenta appears to be capable of actively transporting iodide to maintain a foetal to maternal iodide ratio of up to 8:1.
Foetal thyroxine utilization was of the same order at 111 days of gestation as immediately before parturition when expressed per unit body weight. Utilization of thyroxine per kg by the foetus was about five times that of the mother. Various factors which influence thyroid function are discussed and the activity of the foetal pituitary—thyroid system is compared with other foetal endocrine systems.
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Body reserves (long-term) and food intake (short-term) both contribute nutritional feedback to the hypothalamus. Reproductive neuroendocrine output (GnRH/LH) is stimulated by increased food intake and not by high adiposity in sheep, but it is unknown whether appetite-regulating hypothalamic neurons show this differential response. Castrated male sheep (Scottish Blackface) with oestradiol implants were studied in two 4 week experiments. In Experiment 1, sheep were fed to maintain the initial body condition (BC) score of 2.0+/-0.00 (lower BC (LBC), n=7) or 2.9+/-0.09 (higher BC (HBC), n=9), and liveweight of 43+/-1.1 and 59+/-1.6 kg respectively. LBC and HBC sheep had similar mean plasma LH concentration, pulse frequency and amplitude, but HBC animals had higher mean plasma concentrations of insulin (P<0.01), leptin (P<0.01) and glucose (P<0.01). Gene expression (measured by in situ hybridisation) in the hypothalamic arcuate nucleus (ARC) was higher in LBC than HBC sheep for neuropeptide Y (NPY; 486% of HBC, P<0.01), agouti-related peptide (AGRP; 467%, P<0.05) and leptin receptor (OB-Rb; 141%, P<0.05), but lower for cocaine- and amphetamine-regulated transcript (CART; 92%, P<0.05) and similar between groups for pro-opiomelanocortin (POMC). In Experiment 2, sheep with initial mean BC score 2.4+/-0.03 and liveweight 55+/-0.8 kg were fed a liveweight-maintenance ration (low intake, LI, n=7) while sheep with initial mean BC score 2.0+/-0.03 and liveweight 43+/-1.4 kg were fed freely so that BC score increased to 2.5+/-0.00 and liveweight increased to 54+/-1.4 kg (high intake, HI, n=9). Compared with LI, HI sheep had higher mean plasma LH (P<0.05), baseline LH (P<0.01) and pulse amplitude (P<0.01) and showed a trend towards higher pulse frequency. Although there were no differences in final mean plasma concentrations, there were significant increases over time in mean concentrations of insulin (P<0.001), leptin (P<0.05) and glucose (P<0.001) in HI sheep. Gene expression for AGRP in the ARC was higher in HI than LI animals (453% of LI; P<0.05), but expression levels were similar for NPY, OB-Rb, CART and POMC. Thus, the hypothalamus shows differential responses to steady-state adiposity as opposed to an increase in food intake, in terms of both reproductive neuroendocrine activity and hypothalamic appetite-regulating pathways. Differences in hypothalamic gene expression were largely consistent with contemporary levels of systemic leptin and insulin feedback; however, increased nutritional feedback was stimulatory to GnRH/LH whereas constant high feedback was not. The hypothalamus therefore has the ability to retain a nutritional memory that can influence subsequent responses.
