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Lewin Small, Henry Gong, Christian Yassmin, Gregory J Cooney and Amanda E Brandon

animal research facilities is usually 20–24°C, a temperature range where clothed humans are most comfortable. This environment however, may subject the rodents to mild but chronic cold stress because the thermoneutral temperature for rodents is closer to

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Holly M Johnson, Erin Stanfield, Grace J Campbell, Erica E Eberl, Gregory J Cooney and Kim S Bell-Anderson

rats causes profound whole-body and tissue-specific insulin resistance and is a routinely used means of inducing metabolic dysfunction in rodent models. In 1987, Storlien et al. clearly showed that under isocaloric conditions, dietary fat subtypes

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R. Fraser

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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M. van den ENDE

Hormones of known chemical structure have been artificially linked to proteins to form antigens in which the hormone acts as specific haptene. Immunization with such an artificial hormone antigen will result in the production of antibodies capable not only of forming a precipitate with the complete antigen or with the hormone haptene in vitro but also of inhibiting the characteristic physiological action of the whole antigen or the haptene when this is administered parenterally to test animals [Clutton, Harington & Yuill, 1938].

In spite of numerous attempts, however, it has hitherto not been possible to establish the antibody nature of the antihormones evoked by the prolonged administration of natural hormone extracts. The majority of investigators have used crude extracts of the anterior lobe of the hypophysis as immunizing antigens. The use of such crude extracts has invariably yielded sera which, in addition to antihormones, contain antibodies specific for antigens characteristic

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J. B. Koea, B. W. Gallaher, B. H. Breier, R. G. Douglas, S. Hodgkinson, J. H. F. Shaw and P. D. Gluckman

ABSTRACT

Primed constant infusions of [14C]urea were used to determine the acute effect of passive immunization against circulating free and protein-bound insulin-like growth factor-I (IGF-I) on the rate of net protein catabolism (NPC) in castrated male lambs fasted for 48 h. Following an intravenous bolus of 50 ml IGF-I antiserum, the rate of NPC increased to a peak 30 min after injection of 1·69 ± 0·16 g/kg per day from a baseline value of 1·45±0·22 g/kg per day (P<0·05, n = 4). In three animals given 50 ml equivalents of the purified immunoglobulin fraction, NPC increased from 1·31 ±0·20 to 1·59±0·16 g/kg per day (P<0·05). A similar trend was observed in animals given 25 ml antiserum (n = 4). The rate of NPC did not increase following a bolus of non-immune serum in control animals and the rate of NPC in the treated lambs returned to control levels within 60 min of antibody injection. Plasma insulin and glucose concentrations in both the treated and control groups were unchanged throughout the study. These data suggest that circulating IGF-I has a physiological role in regulating whole body protein turnover during starvation and possibly other catabolic states. The effect of immunoneutralization of circulating IGF-I is transient and this suggests that while IGF-I has an endocrine role in the regulation of protein turnover, other regulatory mechanisms are involved.

Journal of Endocrinology (1992) 135, 279–284

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D. E. Kerr, B. Laarveld and J. G. Manns

ABSTRACT

The physiological importance of circulating as opposed to locally produced insulin-like growth factor-I (IGF-I) has not been determined. By using a passive immunoneutralization technique, our objectives were to evaluate the role of circulating IGF-I in the regulation of animal growth and pituitary GH content.

A monoclonal antibody (MAb) to IGF-I, generated in our laboratory, has an affinity (K a) of 0·13 litres/pmol for recombinant human IGF-I (rhIGF-I). Cross-reactivities of recombinant des-tripeptide IGF-I and recombinant bovine IGF-II were approximately 40 and 8% respectively. This MAb inhibited binding of purified hIGF-I to human placental membranes. In a radioimmunoassay based on displacement of 125I-labelled rhIGF-I from the MAb, displacement curves generated with dilutions of acid–gel chromatography extracts of guinea-pig serum and rhIGF-I standards were parallel.

Twenty-four, 3-week-old male guinea-pigs were treated with the IGF-I MAb, a bovine herpes virus-I (BHV-I) MAb (control MAb) or vehicle (phosphate-buffered saline) (n = 8 per group). Treatments were administered i.p. every 3 days for 24 days at a dose of 20 mg/kg body weight. Blood was obtained on day 23 (48 h after treatment) and on day 25 (24 h after treatment). In a liquid-phase assay, serum from the IGF-I MAb-treated group bound 38 ± 8% (mean ± s.e.m.) (day 23) and 56 ± 7% (day 25) of an 125I-labelled rhIGF-I trace at a final dilution of 1:10 000. Because of the development of an anti-mouse immune response in the guinea-pigs, these parameters would probably have been much greater during the first 2 weeks of the trial. Of the total IGF-I in serum, 50 ± 5% and 61±4% could be immunoprecipitated with an excess of rabbit anti-mouse immunoglobulin in samples from days 23 and 25 respectively. Comparisons between the groups treated with IGF-I MAb and BHV-I MAb revealed no significant differences in whole animal growth rate, growth of individual tissues, or pituitary GH content. Mean serum concentrations of IGF-I were 69 and 99% greater in IGF-I MAb-treated group than in the BHV-I MAb-treated group on days 23 and 25 respectively. These differences probably resulted from an extension of the half-life of IGF-I in serum of animals treated with the IGF-I MAb.

The lack of effect of treatment with the IGF-I MAb suggests that local production of IGF-I is generally sufficient to maintain normal growth or that local production or activity of IGF-I is increased in a compensatory fashion.

Journal of Endocrinology (1990) 124, 403–415

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J H Shand, D W West and D J Flint

Lactating rats were treated for 48 h with bromocriptine (to inhibit prolactin release) or bromocriptine together with an antiserum to rat GH. Animals given the combined treatment were also supplemented concurrently with bovine GH (bGH) or human insulin-like growth factor-I (hIGF-I). The effects of these treatments on the activities of 3-methyl-3-glutaryl-CoA reductase (HMG-CoA reductase), acyl-CoA:cholesterol acyltransferase (ACAT) and neutral cholesteryl ester hydrolase (CEH) and on the microsomal concentrations of non-esterified and esterified cholesterol were measured.

Lack of prolactin decreased HMG-CoA reductase but did not affect ACAT, neutral CEH or the concentrations of microsomal cholesterol or cholesteryl esters. In the absence of both hormones, an even greater reduction in HMG-CoA reductase together with increases in ACAT, neutral CEH and both of the microsomal sterols were observed. Concurrent supplementation with either bGH or hIGF-I wholly or partially prevented the effects on HMG-CoA reductase but only bGH was active against the increase in ACAT. Neither bGH nor hIGF-I could prevent the effects of the anti-hormone treatment on neutral CEH, and the changes in ACAT and CEH activities were broadly reflected in the microsomal sterol concentrations.

The results indicate that the cessation of lactation brings about rapid changes in the activities of the enzymes involved in cholesterol metabolism within the mammary gland with a definite switch from synthesis to storage. Supplementation with bGH alone was sufficient to maintain cholesterol synthesis at control levels and could also significantly inhibit storage of the sterol as its ester. In the absence of GH, hIGF-I partially supported cholesterol synthesis but had no effect on its conversion to the ester. On a whole-tissue basis, enzyme activities could be correlated with the physiological effects of the anti-hormone treatments.

Journal of Endocrinology (1997) 152, 447–454

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Adrian J L Clark and Julian R E Davis

models, and this has coincided with an explosion in our understanding of the molecular and genetic basis of endocrine function. As this molecular understanding has developed it has become essential to try to integrate this with the whole organism, and

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Amanda E Brandon, Ella Stuart, Simon J Leslie, Kyle L Hoehn, David E James, Edward W Kraegen, Nigel Turner and Gregory J Cooney

showed that, similar to younger animals ( Hoehn et al . 2010 ), older Acc2 −/− mice showed increased whole-body FAO (24 h average RER=0.95±0.02 and 0.92±0.02 for WT and Acc2 −/− mice respectively, P <0.05; Fig. 2A and B ). This occurred without

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Natalia Ogonowski, Giselle Piro, Déborah Pessah, Noelia Arreche, Bernardita Puchulu, Ana M Balaszczuk and Andrea L Fellet

these changes are involved in haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Materials and methods Animals Male Sprague-Dawley rats 2months old from the breeding laboratories of the ‘Facultad de Farmacia y