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E M de Vries Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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H C van Beeren Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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M T Ackermans Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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A Kalsbeek Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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E Fliers Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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A Boelen Department of Endocrinology and Metabolism, Hypothalamic Integration Mechanisms, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

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 °C until analysis. The right liver lobe was dissected, snap frozen in liquid nitrogen, and stored in −80 °C until further use. For the food restriction experiment, 24-h food intake was monitored for 4 days (baseline value). Subsequently, rats daily

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Renata Lopes Araujo
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Bruno Moulin de Andrade
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Álvaro Souto Padron de Figueiredo
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Monique Leandro da Silva
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Michelle Porto Marassi
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Valmara dos Santos Pereira
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Eliete Bouskela Laboratório de Fisiologia Endócrina do Instituto de Biofísica Carlos Chagas Filho, Laboratório de Pesquisas em Microcirculação, Universidade Federal do Rio de Janeiro, Rio de Janeiro, CEP 21949-900, Brazil

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Denise P Carvalho
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Introduction Moderate reduction in caloric intake has well-known systemic consequences, including weight loss and a decrease in fat mass; however, homeostatic mechanisms impair further weight loss after long periods of food restriction, such as the

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Fernando Escrivá Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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M Lucía Gavete Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Yasmín Fermín Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Coralia Pérez Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Nilda Gallardo Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Carmen Alvarez Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Antonio Andrés Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Manuel Ros Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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José M Carrascosa Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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months of moderate food restriction which is sufficient to lower visceral adiposity to values even below those of mature 3-month-old rats fed ad libitum . The effects of ageing and food restriction on adipocyte-derived factors such as resistin

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Rakefet Pando Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Majdi Masarwi Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Biana Shtaif Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Anna Idelevich Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Efrat Monsonego-Ornan Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Ron Shahar Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Moshe Phillip Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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Galia Gat-Yablonski Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Robert H. Smith Faculty of Agriculture, Faculty of Agricultural, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Petach Tikva, Israel

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food restriction (RES) and CU growth on bones, we used young, rapidly growing rats. In this experimental model, 40% RES was initiated on 24 days old rats and continued during the linear growth period for 10 days. In our previous studies, we have shown

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PJ Scarpace
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M Nicolson
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M Matheny
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To determine the effects of food restriction and leptin administration on several transcripts involved in energy homeostasis, we examined leptin, uncoupling proteins (UCP) 1, 2 and 3, lipoprotein lipase (LPL), beta3-adrenergic receptors (beta3AR) and hormone-sensitive lipase (HSL) mRNA levels in brown adipose tissue (BAT) and epididymal (EWAT) and perirenal (PWAT) white adipose tissue in three groups of rats. The groups were administered leptin for 1 week, or had food restricted to the amount of food consumed by the leptin-treated animals, or had free access to food. Leptin administration increased serum leptin concentrations 50-fold and decreased food consumption by 43%, whereas serum insulin and corticosterone concentrations were unchanged. Leptin increased LPL mRNA by 80%, UCP1 mRNA twofold, and UCP3 mRNA levels by 62% in BAT, and increased UCP2 mRNA levels twofold in EWAT. In contrast, UCP2 mRNA levels were unchanged in PWAT and BAT. In WAT from food-restricted rats, leptin gene expression was diminished by 40% compared with those fed ad libitum. With leptin administration, there was a further 50% decrease in leptin expression. LPL mRNA levels were decreased by food restriction but not by leptin in WAT, whereas beta3AR and HSL mRNA levels were unchanged with either food restriction or leptin treatment. The present study indicates that leptin increases the gene expression of UCP2 in EWAT and that of UCP1, UCP3 and LPL in BAT, whereas reduced food consumption but not leptin, decreases LPL expression in WAT. In addition, with leptin administration there is a decrease in leptin gene expression in WAT, independent of food intake and serum insulin and corticosterone concentrations.

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A Sohlstrom
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A Katsman
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KL Kind
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PA Grant
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PC Owens
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JS Robinson
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JA Owens
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The effect of fasting (17-18 h) versus food restriction (70% for 80 +/- 13 days) on the IGF-IGF binding protein (BP) axis in female guinea pigs was studied and related to body weight, weight gain and food conversion efficiency. Circulating IGF-I was reduced in the fasted (13%) and food-restricted (50%) animals. IGF-II was only decreased (61%) in the food-restricted group. There was no effect of fasting on IGFBP-1 to -4 while IGFBP-1, -3 and -4 were reduced by 56%, 60% and 44% respectively, and IGFBP-2 increased by 72%, in the food-restricted group. Food restriction reduced the relative sizes of fat depots, spleen, liver, thymus and heart, increased those of adrenals, kidneys, pancreas, gastrointestinal tract, M. Biceps, M. Soleus and brain while those of uterus, lungs, thyroids and M. Gastrocnemius were unchanged. IGFBP-1 and -2 were negatively correlated to weight gain and food conversion efficiency in the ad libitum-fed group, while IGF-I, -II, IGFBP-1, -3 and -4 were positively correlated to body weight, weight gain and food conversion efficiency in the food-restricted group. The results show that acute and chronic food restriction have different consequences for the IGF-IGFBP axis. Furthermore, IGF-II as well as IGF-I are implicated in the control of body weight, weight gain and food conversion efficiency under conditions of restricted nutrition. Finally, IGFBP-1 and -2 may have different roles during chronic undernutrition compared with unrestrained nutrition in adult life.

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J P H Wilding
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M O Ajala
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P D Lambert
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S R Bloom
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Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and rates of synthesis and release in the hypothalamus correlate closely with nutritional status. Pregnancy and lactation provide an excellent model of physiological hyperphagia. In this study the authors measured food intake, plasma glucose, insulin and luteinizing hormone (LH) and hypothalamic NPY mRNA in rats during pregnancy and in early and late lactation. The effect of food restriction (to 80% of control) during lactation was also studied. Pregnancy resulted in a modest increase in daily food intake over non-lactating controls (controls: 15·6±0·6 g, pregnant: 19·8±1·1 g, P<0·01) During lactation food intake increased dramatically to 355% of non-lactating levels by the 12th day. Insulin and glucose levels were unchanged in lactation, except in the food-restricted animals, when insulin levels were reduced to 49·5±18·4 pmol/l compared with 215±55 pmol/l (P<0·01) in lactating, non-restricted animals, and glucose was reduced to 3·7±0·2 mmol/l compared with 5·1 ± 0·2 mmol/l in non-restricted lactating animals. Hypothalamic NPY mRNA was unchanged in pregnancy, moderately increased after 5 days lactation (130±6·2% of control, P<0·01) and increased further at 14 days lactation (179 ± 14%, P<0·001). The greatest changes occurred in the animals who were food-deprived during lactation, when hypothalamic NPY mRNA levels reached 324 ± 44% (P<0·001) of non-lactating levels. Increases in hypothalamic NPY synthesis may be partly responsible for the increase in food intake seen in lactation, but unlike in food deprivation, the increase is not related to circulating insulin, suggesting involvement of other regulatory factors.

Journal of Endocrinology (1997) 152, 365–369

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G Wiesner
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BA Morash
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E Ur
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M Wilkinson
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White adipose tissue is now recognized as the source of a growing list of novel adipocyte-specific factors, or adipokines. These factors regulate energy homeostasis, including the response to food deprivation. We hypothesized that the brain and pituitary gland would also express adipokines and their regulatory factors and subsequently demonstrated that the rodent brain-pituitary system expresses mRNA and protein for leptin and resistin. We now report that the adipokines FIAF and adiponutrin, as well as the nuclear hormone receptor PPAR gamma, are expressed in pituitary, brain and adipose tissue. In pituitary gland, 24 h of food restriction reduced PPAR gamma expression by 54% whereas both adiponutrin and FIAF were increased 1.7 and 2.3 fold, respectively. These changes in expression were similar to those observed in fat, except for adiponutrin, which by contrast is dramatically reduced 95% by fasting. Furthermore, whereas PPAR gamma 2 is the main isoform affected by fasting in adipose tissue, our data suggest that only PPAR gamma 1 is present and downregulated by fasting in pituitary tissue. In contrast to the sensitivity of pituitary tissue to the effects of fasting, no significant change in expression was observed in basal hypothalamus for any of the genes studied. Overall, our data suggest that pituitary-derived adipokines may play an unexpected role in the neuroendocrine regulation of energy homeostasis.

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BA Henry
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A Rao
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AJ Tilbrook
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IJ Clarke
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Changes in the secretion of GH induced by long-term alterations in nutritional status are thought to result from alterations in somatostatin (SRIF) and growth hormone-releasing hormone (GHRH) at the level of the hypothalamus. To date however, the effect of nutrition on the gene expression of SRIF and GHRH in a species where GH secretion is increased by food restriction, as is the case for the sheep and human, remains unknown. We determined the effect of under-nutrition on the expression of SRIF and GHRH in the hypothalamus of sheep. Ovariectomised ewes were randomly divided into two groups and either fed an ad lib diet (n=6) or a restricted diet of 500 g lucerne chaff per day (food-restricted; n=5) for 7 months. In situ hybridisation was used to study hypothalamic gene expression for GHRH, SRIF and galanin (GAL). The food-restricted animals had elevated plasma concentrations of GH; this was associated with an increase in GHRH mRNA levels in the arcuate nucleus (ARC) and reduced SRIF in the rostral periventricular nucleus and ventromedial hypothalamic nucleus. The level of gene expression of GAL in the ARC and SRIF in the caudal periventricular nucleus was similar in ad lib and food-restricted animals. In conclusion, the effect of chronic food-restriction on the secretion of GH reflects increased GHRH and reduced SRIF synthesis in the hypothalamus.

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M H Monaco
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S M Donovan
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Abstract

The role of somatogenic and lactogenic hormones in the adaptative mechanisms which occur in response to nutrient restriction during lactation is unknown. To characterize the effect of food restriction during lactation on serum IGF-I, GH and prolactin concentrations and serum IGF-binding protein (IGFBP) profiles, lactating dams had free access to food (control) or were restricted to 60% of control intake during pregnancy and lactation (RPL) or only during lactation (RL). Serum, milk and mammary gland samples were collected throughout lactation. RL dams lost body weight, control dams gained weight, while RPL dams maintained body weight during lactation. By day 20, body and mammary gland weights of RL and RPL dams did not differ and were lower than control (P<0·05). Serum IGF-I concentrations in restricted groups were lower than control (P<0·05), however, hepatic expression of IGF-I mRNA did not differ between groups in early (day 1) or mid-lactation (day 8) and was increased on day 20 in RL dams compared with RPL or control. These data suggest that serum IGF-I and hepatic IGF-I mRNA expression are not co-ordinately regulated in the food-restricted lactating rat. In early lactation, serum IGFBP-3 was lower in RPL dams than control (P<0·05), whereas IGFBP-1 and -2 were increased in RL and RPL dams in late lactation compared with control. The decrease in IGFBP-3 and increase in lower molecular weight IGFBP may have contributed to the reduction in serum IGF-I by increasing IGF-I clearance from the circulation. Serum GH and prolactin were measured in samples obtained between 0900 and 1200 h. Serum GH did not differ with the exception of an increase on day 1 in control relative to RPL dams and on day 20 in RL dams relative to RPL and control. Serum prolactin was higher in the RL dams than controls on day 4. In summary, food restriction during pregnancy and lactation or solely during lactation results in similar reductions in serum IGF-I and alterations in serum IGFBP despite differences in body weight responses to food restriction during lactation.

Journal of Endocrinology (1997) 152, 303–316

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