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M R Wilson
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S J Hughes
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Abstract

To test the hypothesis that poor foetal–neonatal nutrition predisposes adult animals to impaired glucose tolerance or diabetes, pregnant and lactating rats were fed a low (5%) protein diet and glucose tolerance and pancreatic islet function then assessed in the adult offspring. To expose any underlying defects the offspring were allowed access to a sucrose supplement (35%) or fed a high fat diet. Offspring born to low protein-fed females had significantly lower body weights than controls. In islets from previously malnourished rats, insulin release in batch incubations or perifusion was not significantly different to controls. In islets from previously malnourished animals fed sucrose, glucose-stimulated insulin release was reduced in perifusion by 66% (P<0·01) and batch incubations by 26–52% (6–16 mmol/l glucose, (P<0·01). Similarly, impaired secretory responses were found in islets from previously malnourished animals fed a high fat diet. These did not result from a reduced pool of releasable insulin, as arginine-stimulated secretion was not impaired. Rats previously malnourished showed a normal glucose tolerance. Glucose tolerance was impaired, however, in previously malnourished rats fed sucrose (area under the glucose tolerance test curve was increased by 42%, P<0·05) but despite the reduced islet secretory responses was not significantly different to sucrose-fed controls (area increased by 54%, P<0·05). Glucose tolerance was impaired in previously malnourished animals fed high fat diet (area increased by 48%, P<0·05) more so than in high fat fed-controls (28% increase, NS). These data support the hypothesis that poor foetal–neonatal nutrition leads to impaired pancreatic β-cell function which persists into adult life. Alone this is not sufficient to produce diabetes, but an inability to respond to a highly palatable fat diet may tip the balance towards impaired glucose tolerance.

Journal of Endocrinology (1997) 154, 177–185

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G. M. MASSON
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G. R. WILSON
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SUMMARY

There was no diurnal variation in plasma oestriol and diet, exercise and rest did not affect plasma oestriol levels in pregnant women. The 30-min, 3-h and day-to-day coefficients of variation compared favourably with that of 48-h urinary excretion.

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D. M. Wilson
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R. L. Hintz
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To explore the structural differences in various animal somatomedins, we examined the sera of 20 animal species using two region-specific radioimmunoassays, a radioimmunoassay specific for somatomedin-C and a placental membrane radioreceptor assay. Using small peptide portions of the insulin-like growth factor-I (IGF-I) C chain and D chain made by solid-state methods, we generated antisera in rabbits and developed radioimmunoassays to these regions. For a radioimmunoassay directed against intact somatomedin-C, we used the antibody distributed by the NIH (NIH-radioimmunoassay). For the detection of somatomedin peptide content, we used a placental membrane radioreceptor assay. 125I-Labelled IGF-I was used as the radioligand in all assays and an insulin-free, partially purified somatomedin preparation was used for the standard curves. All samples were chromatographed in 0·25 m-formic acid to remove any somatomedin-binding protein before assay.

The correlation between the radioreceptor assay and the NIH-radioimmunoassay was good (r 2 = 0·84) but the slope was significantly (P<0·001) different from a value of 1 which would be expected if the two assays were detecting equal amounts of somatomedin activity. In all the species, the somatomedin level measured by radioreceptor assay was greater than that measured by the NIH-radioimmunoassay, suggesting the presence of a somatomedin-like protein which has retained its ability to bind to the somatomedin receptor but which is sufficiently different to give it reduced affinity in the NIH-radioimmunoassay.

The somatomedins of rat, hamster and mouse (all rodents of the superfamily Myomorpha) were not detectable using the radioimmunoassays for the C and D chains of IGF-I, although they were high in the radioreceptor assay. This suggests that these regions have a different structure from the analogous regions in the guinea-pig (a rodent of the superfamily Caviomorpha) and implies a significant structural change in a somatomedin-like molecule during the evolution of the order Rodentia. This is analogous to the marked differences in the known sequence of the pro-insulins in these two superfamilies.

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K. M. KENDRICK
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R. F. DREWETT
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C. A. WILSON
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Measurements of the refractory period of stria terminalis neurones that are sensitive to testosterone propionate, of sexual behaviour and of plasma levels of LH were taken in castrated rats at various times after initiation of treatment with testosterone propionate. Levels of LH dropped within 24 h, before there was any change in neuronal refractory periods. The period of latency to mounting, however, was reduced to its shortest only after 7–8 days and ejaculations first occurred at the same time; these sexual responses correlated in time with the reduction of the neuronal refractory period to its lowest level.

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R. J. WILSON
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GILLIAN M. CRAIG
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I. H. MILLS
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SUMMARY

A case of phaeochromocytoma with hypokalaemia, hyperaldosteronism, normal cortisol production and normal urinary corticosteroid excretion is described. Both α-adrenergic blockade and combined α and β blockade resulted in marked antidiuresis with urinary sodium and potassium retention and a rise in plasma volume. Combined α and β blockade led to some reduction in the high aldosterone production rate. The hypokalaemia was corrected by α-adrenergic blockade. After operative removal of the tumour the aldosterone production rate was normal.

The marked reduction in urinary sodium excretion in response to α-adrenergic blockade, if reproducible in other cases of phaeochromocytoma, might be a useful test for the presence of a phaeochromocytoma.

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R C Olney
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D M Wilson
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M Mohtai
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P J Fielder
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R L Smith
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Abstract

IGF-I is the major anabolic factor for cartilage matrix production. Chondrocytes and cartilage treated with interleukin-1α (IL-1α), and chondrocytes from several models of inflammatory joint disease, exhibit reduced responsiveness to IGF-I. Since the IGF-binding proteins (IGFBPs) modulate the effects of IGF-I, we examined the effect of IL-1α and tumor necrosis factor-α (TNF-α) on IGFBP production by normal human articular chondrocytes in primary culture. Western ligand blots and immunoprecipitation of conditioned medium samples showed that articular chondrocytes produced IGFBPs-2, −3 and −4 and glycosylated IGFBP-4. Both IL-1α and TNF-α increased chondrocyte production of IGFBP-3, but did not alter IGFBP-4 production. The activity of a neutral metalloprotease with the ability to cleave IGFBP-3 was also increased by IL-1α. These data suggest that the cytokines IL-1α and TNF-α may act to reduce IGF-I access to chondrocytes by increasing production of IGFBP-3. This may be a factor in the decreased matrix production in the inflammatory arthritides.

Journal of Endocrinology (1995) 146, 279–286

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C O Lemley
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K A Vonnahme Division of Animal and Nutritional Sciences, Department of Animal Sciences, Davis College of Agriculture, Natural Resources and Design, West Virginia University, Morgantown, West Virginia 26506, USA

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L R Tager
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K M Krause
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M E Wilson
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Elevated rates of steroid clearance may lead to lower reproductive success in several mammalian species. Cytochrome P450 (EC 1.14.14.1) and aldo-keto reductases (AKR; EC 1.1.1.145–151) are involved in the first phase of steroid inactivation, before second phase conjugation and excretion of the steroid metabolite. The current objectives were to determine liver blood flow (LBF), hepatic enzyme activity, and metabolic clearance rate (MCR) of progesterone (P4) in dairy cows consuming isoenergetic and isonitrogenous diets formulated to cause divergent insulin secretion. Insulin concentrations increased by 22% in cows fed the high cornstarch diet, and both cytochrome P450 2C and cytochrome P450 3A activities were decreased (P<0.05) by ∼50%, while AKR1C tended (P<0.10) to be lower in cows fed the high cornstarch diet. LBF was similar between the two diets (1891±91 l/h). MCR of P4 tended (P<0.10) to be lower in cows fed the high cornstarch diet (25±5 l/h×BW0.75) versus the high fiber diet (40±6 l/h×BW0.75). The half-life of P4 was increased (P<0.05) in cows fed the high cornstarch diet (73±10 min) versus the high fiber diet (24±10 min). In summary, cows with elevated insulin concentrations and lower enzyme activity showed a decrease in P4 clearance without any changes in LBF. This dietary relationship with hepatic enzyme activity may explain some of the observed alterations in steroid profiles during the estrous cycle or gestation of the high producing dairy cow.

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J.A. Franklyn
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M. Wilson
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J.R. Davis
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D.B. Ramsden
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K. Docherty
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M.C. Sheppard
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ABSTRACT

We have reported previously the effect of thyroid status in vivo on pituitary cytoplasmic concentrations of messenger RNA (mRNA) encoding the thyrotrophin (TSH) β-subunit (Franklyn, Lynam, Docherty et al, 1985). Studies in vitro of the regulation of TSH β gene transcription have been confined to thyrotrophic tumour cells. We now report the demonstration of TSH β-subunit mRNA in non-tumorous rat pituitary cells in primary culture. Treatment of cells with thyrotrophin-releasing hormone (TRH) and with forskolin resulted in a marked increase in cellular concentration of TSH β-mRNA. These results suggest that TRH exerts a direct effect on the pretranslational events involved in TSH synthesis and further that the adenylate cyclase system may be involved in the regulation of synthesis. We have thus described a novel system for the study of TSH β-subunit gene expression in normal rat pituitary cells in vitro.

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R. F. Walker
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D. W. Wilson
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P. L. Truran
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G. F. Read
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G. Richards
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S. M. Walker
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D. Riad-Fahmy
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ABSTRACT

Salivary progesterone concentrations were measured in daily samples collected between 08.00 and 09.00 h throughout the menstrual cycle of women with a history of fertility. The luteal-phase salivary progesterone profiles in these normally menstruating, healthy women were characterized using a computer program based on a cumulative sum procedure. This method of statistical analysis led to the development of a 'progesterone boundary diagram', the inner and outer domains of which distinguished between the profiles of salivary progesterone considered compatible with fertility, and those observed in subfertile women attending an infertility clinic.

J. Endocr. (1985) 104, 441–446

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C. A. Wilson
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M. B. ter Haar
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R. C. Bonney
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J. Buckingham
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A. F. Dixson
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T. Yeo
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We have shown previously that pregnant mare serum gonadotrophin (PMSG) induces ovulation only in rats weighing over 60 g on the day of injection. The under-60 g rats do not ovulate although they secrete a preovulatory surge of a pleiomorphic form of LH. Presumably this pleiomorph is inactive.

Comparisons were made of plasma hormone concentrations in rats treated with PMSG that weighed over and under 60 g. The measurements were made on samples taken between 13.00 and 22.00 h on the day of the expected preovulatory LH surge. Prolactin and corticosterone levels were lower in the lighter group compared with the heavier group. A midday pulse of GH detected in the over-60 g animals did not occur in the under-60 g group. Levels of ACTH were slightly higher in the under-60 g rats and together with the low corticosterone concentrations indicate adrenal insensitivity. Oestradiol, progesterone and TSH concentrations were the same in the two groups. Since progesterone secretion is under LH control, the 'inactive' pleiomorphic form of LH must have steroidogenic activity. There was an indication that the under-60 g rats also secreted a pleiomorphic form of FSH.

Reports in the literature indicate that prolactin, corticosterone and GH have a positive modulatory influence on natural puberty. They may also influence precocious puberty induced by PMSG, since in the unresponsive under-60 g rat plasma levels of these three hormones were low. Perhaps the release of one or more of these hormones is dependent upon the physical maturity of the animal as represented by body weight.

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