Neural levels of cholecystokinin peptide and mRNA during dietary stimulation of growth and LH secretion in growth-retarded lambs

Chronic feed restriction of prepubertal male lambs adversely affects reproductive development by inhibiting the pulsatile release of luteinizing hormone (LH). Because this effect can be reversed by ad libitum feeding, the associations between diet-induced increases in LH release and concurrent changes in body weight gain, serum glucose. CCK peptide, and CCK mRNA were examined. Neonatally castrated male lambs received a restricted ration to maintain their respective weaning weights beginning at 8 wk of age. At 23 wk of age, lambs were assigned randomly to receive additional feed equivalent to 0%, 50%, or 100% of their previous daily intake. Serum profiles of LH and glucose were determined 2 and 4 wk after onset of the increased intakes. At 27 wk of age, lambs were euthanized and both hypothalamic and cerebral cortical tissues were collected for analysis of CCK peptide and CCK mRNA. With additional intakes, body weight gain increased (P < 0.001) proportional to the graded increases in feed intake. Mean serum LH concentrations, LH peak frequencies, and serum glucose concentrations also increased (P < 0.05) progressively among the 0%, 50%, and 100% dietary intake groups. Neither CCK peptide nor CCK mRNA differed (P > 0.05) among dietary groups suggesting that endogenous CCK in the whole hypothalamus did not change with the feeding-induced increase in LH release. Concentrations of CCK peptide in cerebral cortex were greater (P < 0.05) than hypothalamic concentrations, but there were no differences between hypothalamus and cerebral cortex in the relative abundance of CCK mRNA. In summary, dietary stimulation of growth-retarded male lambs resulted in progressive increases in body weight gain, mean serum LH, serum glucose, and LH peak frequencies. Because hypothalamic levels of CCK peptide and CCK mRNA did not change during feeding-induced secretion of LH, endogenous CCK in the hypothalamus seems unlikely as a chronic mediator of nutrition-sensitive LH release.     

Immunological studies in patients with mumps orchitis

A study of the effect of restriction of feed intake on the deiodination, faecal excretion, distribution and secretion of thyroid hormones was carried out in a group of eight young male goats. In the control goats fed ad libitum no changes in the concentration of circulating thyroxine were observed with increasing age or body weight during the experimental period; however, an increase in thyroxine secretion rate per animal was apparent with increasing age or body weight of the goats. In feed-restricted goats, no changes in the peripheral deiodination of [125I]thyroxine were observed, though significantly reduced faecal excretion of [125I]thyroxine was seen in goats restricted to 50 or 20% of their ad libitum feed intake. Both thyroxine turnover rate and thyroxine distribution volume were reduced by feed restriction. The secretion rate of thyroxine was reduced to 45% of the rate in ad libitum fed animals when feed intake was restricted to 20%. Calculation of thyroxine secretion rate per kilogram 0-75 body weight showed a highly significant correlation with feed intake. It was concluded that the marked reduction in thyroid activity occurring when feed restriction was imposed would be expected to cause a physiologically significant reduction in metabolic activity.     

Effects of food restriction on the periodicity of corticosteroids in plasma and on monoamine concentrations in discrete brain nuclei

The concentrations of plasma corticosteroids and of norepinephrine, dopamine and serotonin in microdissected brain regions were measured at 08.00, 12.00 and 20.00 h in male rats fed ad libitum and in rats whose food intake was restricted to 09.30-11.30 h. In ad libitum fed animals, plasma corticosteroids were lowest at 08.00 and highest at 20.00 h. As demonstrated previously, restriction of food availability was associated with appearance of a peak in corticosteroids at 08.00 h. In ad libitum fed animals, serotonin and dopamine concentrations in the median eminence were higher at 20.00 than at 08.00 h. Restriction of food availability significantly decreased the levels of these neurotransmitters at 20.00 h. In the paraventricular nucleus, amygdala, and hippocampus of ad libitum fed animals, serotonin levels were lower at 20.00 than at 08.00 or 12.00 h. In food-shifted animals, this pattern was reversed so that lowest levels of serotonin occured at 08.00 and markedly elevated levels were observed at 12.00 and 20.00 h. No changes were noted in norepinephrine content of the median eminence or paraventricular nucleus of ad libitum fed or food restricted animals. These results indicate that the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regime is accompanied by changes in the periodicity of neurotransmitter concentrations in specific regions of the brain, and that such patterns are dissimilar in different regions.     

Influence of mode and carbohydrate on the cytokine response to heavy exertion

1. This experiment was carried out to evaluate the productive and physiological consequences of a slight but long term food restriction of male broiler chickens from 2 commercial strains. 2. Cobb-500 and Ross chickens were submitted to a 20% food restriction from 8 to 21 d of age. Strain, food programme and their interactive effects were analysed in terms of consequences upon performance, mortality, incidence of sudden death syndrome (SDS) and ascites syndrome (AS), index of right cardiac hypertrophy and plasma concentrations of hormones related to metabolism and growth (T3, T4, T3:T4 ratio, IGF-I and GH). 3. Although some catch-up growth was observed by refeeding previously restricted birds after 22 d of rearing, food restriction decreased (P < or = 0.05) body weight at market age (42 d) irrespective of the strain, but improved (P < or = 0.05) food conversion. 4. The incidence of mortality was not high in non-restricted birds but SDS and AS caused more than 50% of deaths. Hypertrophic cardiac index was observed in chickens of both strains after 4 weeks of age and was higher in ad libitum fed birds. 5. During the period of food restriction, plasma T3 and IGF-I concentrations decreased whereas plasma T4 and GH concentrations increased compared to those of the age-matched ad libitum fed counterparts. During the subsequent ad libitum feeding period, few differences in circulating hormone concentrations were observed, except for the higher mean GH litres in previously food-restricted chickens at 35 d of age. 6. These results indicate that even a non-severe food restriction negatively affects body weight of 42-d-old male broilers but these are benefits with improved food efficiency and diminished mortality from metabolic disturbances. The hormone results suggest that the degree of food restriction applied was not severe because there was a very fast adaptive response with small and transient alterations in T3, T4 and GH plasma concentrations during the period of compensatory growth.     

Changes in iron, calcium, magnesium, copper, and zinc levels in different tissues of riboflavin-deficient rats

To clarify the changes of mineral levels in different tissues of riboflavin-deficient rats, Wistar rats were separated into three groups. One group was fed a diet ad libitum that was deficient in riboflavin. The other two were fed either the complete diet that was weight-matched to the riboflavin-deficient group or fed a complete diet ad libitum. In riboflavin-deficient rats, the hemoglobin concentration and riboflavin contents of blood, liver, and kidney were significantly decreased, compared with weight-matched and ad libitum-fed controls. The mineral concentrations of tissues are summarized as follows: The iron (Fe) concentration in the heart, liver, and spleen was decreased in the riboflavin-deficient group compared with the other groups. Calcium (Ca) and magnesium (Mg) concentrations in tibia were decreased in the riboflavin-deficient group compared with the other two groups. Copper (Cu) concentration was increased in the heart and liver, when the riboflavin-deficient group was compared with the other groups. Zinc (Zn) concentration was increased in tibia when the riboflavin-deficient group was compared with the other groups.     

Effect of aging on the activities of acetylcholinesterase, Na+,K(+)-ATPase and Mg(2+)-ATPase in rat pituitary and hypothalamus

Acetylcholinesterase (AChE), Na+,K(+)-ATPase and Mg(2+)-ATPase activities were estimated in homogenised rat pituitary and hypothalamus of 4- and 22-month-old rats. AChE activity was not altered in the pituitary of aged compared to adult rats, while it was found decreased by about 40% in the hypothalamus. Na+,K(+)-ATPase activity remained stable in the hypothalamus, while it was decreased by about 38% in the pituitary. Mg(2+)-ATPase activity remained unchanged in the hypothalamus, but was increased by about 83% in the pituitary. This pituitary Na+,K(+)-ATPase inactivation may result in pathological mood and decreased neural excitability and metabolic energy production in aged animals. The age-related alterations of AChE, Na+,K(+)-ATPase and Mg(2+)-ATPase activities may reflect changes in secretion and responses of some hormones of pituitary and hypothalamus.     

Modulation of prolactin receptors in the rat hypothalamus in response to changes in serum concentration of endogenous prolactin or to ovine prolactin administration

Specific binding of 125I-labeled rat prolactin (125I-rat PRL) to hypothalamic membranes was studied in Sprague-Dawley rats after ovine PRL administration and in relation to rat PRL serum variations induced by ectopic pituitary implants or by drugs which stimulate (domperidone) or inhibit (bromocriptine) PRL release. Repeated treatments with ovine PRL markedly increased specific binding values of 125I-rat PRL to hypothalamic membranes of female rats. Repeated treatments with domperidone also increased specific PRL binding in the hypothalamus. This effect was associated with an increase in PRL serum levels. Similar results were obtained in male rats after renal pituitary implants which resulted in a state of chronic hyperprolactinaemia. In contrast, a subchronic treatment with bromocriptine decreased specific PRL binding in the hypothalamus and concomitantly caused a sharp reduction in PRL serum levels. Scatchard analysis of data obtained from competition curves showed that the variations in the level of PRL binding to hypothalamic membranes were related to the number of PRL binding sites but not to the dissociation constant (Kd), which was unaffected by different treatments or by pituitary implantation. These results demonstrate a correlation between circulating concentrations of PRL and number of its receptors in the rat hypothalamus and give further support to the hypothesis that these binding sites may have a specific functional role in regulating the homeostasis of pituitary PRL secretion.     

Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator?

Several endogenous oscillators determine circadian rhythms. One, light-entrained, is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and feeding affect rhythms, we compared nocturnally active rats fed either ad libitum or for 2 hr/d during light [restricted feeding (RF)] and either with or without colchicine-induced disruption of VMN. We measured rhythms in temperature, locomotor activity, feeding, drinking, corticosterone, and the numbers of cells expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN, whereas the VMN and sPVNz lacked light/dark differences except after RF and RF plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere maintaining dark > light. By contrast, levels of corticosterone peaked before food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos activity driven by the SCN. The VMN may contain a food-entrained oscillator, and the sPVNz may integrate output from several oscillators.     

Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats

To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.     

Adrenocorticotropic hormone therapy for infantile spasms alters pyruvate metabolism in the central nervous system

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl compounds that are believed to stimulate the release of GH by a direct effect on the pituitary somatotrope and by stimulation of growth hormone-releasing hormone (GHRH) release and the suppression of somatostatin (SRIH) tone. Recently, the receptor for these pharmacologic agents was cloned and its expression localized to the pituitary and hypothalamus. The elucidation of an unique GHS receptor (GHS-R) suggests there is a yet to be identified endogenous ligand which could exert an important role in regulation of GH secretion. It is clearly established that GH acts to regulate its own production by feeding back at the level of the hypothalamus to downregulate GHRH and upregulate SRIH synthesis and by induction of IGF-I, which acts at the pituitary to block somatotrope responsiveness to GHRH. If the endogenous GHS/GHS-R signaling system is important in regulating GH release, it might be reasoned that changes in circulating GH concentrations would also directly or indirectly (via generation of IGF-I) modify GHS-R production. To test this hypothesis we used RT-PCR to examined pituitary and hypothalamic GHS-R mRNA levels in the spontaneous dwarf rat (SDR), an animal model characterized by the absence of GH due to a point mutation in the GH gene. In the absence of GH feedback regulation, SDR pituitary GHS-R mRNA levels were 385 +/- 61% greater (p < 0.01) than those observed in normal controls while SDR hypothalamic GHS-R mRNA levels were not significantly different from those in normal rats. Three-day subcutaneous infusion of rat GH by osmotic pump reduced SDR pituitary GHS-R mRNA levels to 55 +/- 9% of vehicle-treated controls (p < 0.05) but did not significantly alter hypothalamic GHS-R mRNA levels. To test if the changes in GHS-R mRNA levels observed following GH treatment were due to elevation of circulating IGF-I concentrations, SDRs were infused with recombinant human IGF-I. Replacement of IGF-I did not significantly alter either pituitary or hypothalamic GHS-R mRNA levels, indicating that GH acts independent of circulating IGF-I to regulate pituitary GHS-R expression in the SDR model.     

Effect of clenbuterol on growth and body composition during food restriction in rats

Clenbuterol was administered as a dietary admixture (4 mg/kg diet) to three groups of male Wistar rats (n = 8) housed individually in metabolism cages and fed for 15 d at 110, 160, and 235% (ad libitum) of estimated requirement for energy maintenance. Untreated groups at each level of energy intake were also included. There was no effect of clenbuterol on food intake in the ad libitum group, but the drug produced significant increases in body weight, feed efficiency, and carcass weight, dressing and protein content at all three levels of energy intake. This effect of clenbuterol was particularly noticeable in the restricted animals. Clenbuterol caused changes in body composition (increased percentage of water and protein, decreased percentage of fat) in the ad libitum rats but had no effect in the restricted groups. The reduction in the growth of the viscera caused by energy restriction was not affected by clenbuterol, apart from in the 110% restricted group, where the gastrointestinal tract was 26% heavier in the clenbuterol-treated rats. The results show that the growth anabolic actions of clenbuterol can be sustained and may be even more marked in rats fed restrictively than in those given ad libitum access to feed.     

Chicken extract stimulates haemoglobin restoration in iron deficient rats

Chicken essence is widely used as a traditional remedy for several ailments including anaemia. To test this claim for objective evidence, a series of experiments was carried out in anaemic rats by supplementing iron deficient diets with either liquid or lyophilised essence, which contains mainly protein and peptides (83 mg/ml) and free amino acids (3.1 mg/ml), very little iron (1 microgram/ml), and no fat. Haemoglobin returned to normal significantly more rapidly in rats supplemented with ad libitum liquid BEC over a period of up to 27 days compared with controls fed only water in addition to the ad libitum iron deficient diet. Haemoglobin was also significantly increased after 1 week in animals fed ad libitum diets supplemented with lyophilised chicken essence than with controls fed the unsupplemented diet. The effect was greater with supplementation at the level of 0.2% than at 1% lyophilised essence. The results indicate that the effects were mediated by increased appetite and by enhanced availability of food iron. These studies provide objective evidence for the traditional belief that chicken essence remedies anaemia.     

Effects of feeding level on growth, composition of gain, carcass quality and mature body size in steers at ages up to six years

Tissue gain and efficiency and carcass characteristics of seventy-eight Angus steers were compared on three feed intake regimens and serially slaughtered at 6 months to 6 years. The regimens were: (A) continuous ad ad libitum feeding, (B) restricted to gain about 0.45 kg daily and (C) restricted as in B until 6 months before slaughter then fed ad libitum. Steers, regardless of feeding regimen, made their greatest gains up to 12 months of age and became less efficient after that time. Steers fed ad libitum had the highest percentage of fat but the lowest percentage of lean and bone when compared with steers fed for restricted gain. Carcasses of the steers fed ad libitum contained more lean and fat at each slaughter age. Average daily gain, feed efficiency and percentage of lean and bone decreased with age; and feed intake, slaughter grade, dressing percent, taste panel desirability and percent of fat tended to increase with age. All steers reached their maximum growth in height at withers, depth of chest and length of body at about 3 years. Steers that were restricted up to 6 months before slaughter showed compensatory growth during their ad libitum feeding period and during the first 12 months of the study; protein and fat were produced most efficiently by this growth. It would appear that it is possible to modify fat deposition by changing feed intake level.     

Severe experimental uraemia does not decrease the population of rat pituitary somatotrophs

BACKGROUND: Growth hormone (GH) secretion by the anterior pituitary has been shown to be depressed in severely uraemic rats. Changes in the population of pituitary somatotrophs might be partially responsible for this decrease. METHODS: To analyse the population of pituitary somatotrophs in severe uraemia, immunocytochemical detection and quantification of GH-producing cells were carried out on paraffin sections from young rats either 5/6 nephrectomized, sham-operated fed ad libitum or sham-operated pair-fed with the nephrectomized animals. Results: Nephrectomized rats were severely uraemic and growth retarded. The overall cell density (total pituitary cells/mm2) was higher in 5/6 nephrectomized animals in comparison with the two sham-operated groups. Thus, although the percentage of GH cells was slightly lower in nephrectomized than in control rats, no difference in either the density (cells/mm2) or the cross-sectional area of GH cells was found among groups. CONCLUSIONS: These results suggest that severe experimental uraemia interferes with the maturation process of the pituitary gland and support the contention that differences in either the number or the size of pituitary somatotrophs cannot explain the reduced GH secretion previously reported in severely uraemic rats.     

Physiological and pathophysiological aspects of thyrotropin-releasing hormone gene expression in the human hypothalamus

Although the tripeptide thyrotropin-releasing hormone (TRH) was the first hypothalamic hormone to be isolated and characterized, only very few data were available on the central component of the hypothalamus-pituitary-thyroid (HPT) axis in the human brain until recently. We used immunocytochemistry to describe, for the first time, the distribution of TRH-containing cells and fibers in the human hypothalamus. Brain material was obtained with a short postmortem delay followed by fixation in paraformaldehyde, glutaraldehyde, and picric acid. Many TRH-containing cells were present in the paraventricular nucleus (PVN), especially in its dorsocaudal part. Some TRH cells were found in the suprachiasmatic nucleus (SCN), which is the circadian clock of the brain, and in the sexually dimorphic nucleus (SDN), which is in agreement with earlier observations in the rat hypothalamus. Dense TRH-containing fiber networks were present not only in the median eminence but also in a number of other hypothalamic areas, suggesting a physiological function of TRH as a neuromodulator or neurotransmitter in the human brain, in addition to its neuroendocrine role in pituitary secretion of thyroid-stimulating hormone (TSH). As a next step, we developed a technique for TRH mRNA in situ hybridization using a [35S] CTP-labeled TRH cRNA antisense probe in formalin-fixed paraffin-embedded sections. Numerous heavily labeled TRH mRNA-containing neurons were detected in the caudal part of the PVN, while some cells were present in the SCN and in the perifornical area. These results demonstrated the value of in situ hybridization for elucidating the chemoarchitecture of the human hypothalamus in routinely fixed autopsy tissue and enabled us to perform quantitative studies. As part of the neuroendocrine response to disease, serum concentrations of thyroid hormone decrease without giving rise to elevated concentrations of TSH, suggesting altered feedback control at the level of the hypothalamus and/or pituitary. In order to establish whether decreased activity of TRH cells in the PVN contributes to the persistence of low TSH levels in nonthyroidal illness (NTI), hypothalamic TRH gene expression was investigated in patients whose plasma concentrations of thyroid hormones had been measured just before death. Quantitative in situ hybridization showed a positive correlation of total TRH mRNA in the PVN and serum concentrations of TSH and triiodothyronine (T3) less than 24 hours before death, supporting our hypothesis. Current experiments aim at elucidating the mechanism by which hypothalamic thyroid hormone feedback control in TRH cells of patients with NTI is changed.     

Effects of short- and long-term dexamethasone treatment on growth and growth hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in conscious rats

Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX (200 microg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed. Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.     

Intact leptin receptor is selectively expressed in human fetal pituitary and pituitary adenomas and signals human fetal pituitary growth hormone secretion

Leptin, a circulating hormone secreted by adipocytes, communicates peripheral nutritional status to hypothalamic centers affecting satiety, energy expenditure, and body weight. The intact leptin receptor (OB-R), a single membrane-spanning peptide containing an approximately 300-amino acid intracellular domain, is highly expressed in the hypothalamus, whereas shorter OB-R isoforms with truncated cytoplasmic regions resulting from alternative splicing have also been identified. We studied expression of OB-R isoforms in human fetal pituitaries, adult anterior pituitaries, and human pituitary adenomas. Using RT-PCR, messenger ribonucleic acid expression of the OB-R intact isoform was detected in fetal anterior pituitary tissues, but not in adult anterior pituitary glands, whereas both fetal and adult tissues expressed the short forms. Messenger ribonucleic acid of both intact and short OB-R isoforms were expressed in 4 of 5 GH-secreting, all 9 PRL-secreting, and 26 of 29 nonfunctioning pituitary adenomas. Recombinant human leptin (3-6 nmol/L) specifically stimulated GH secretion from primary human fetal pituitary cultures by 40-90% (P < 0.05) without altering fetal ACTH, PRL, or gonadotropin secretion. Thus, the intact OB-R is selectively expressed in human fetal and adult pituitary tumor tissues, but not in normal adult pituitary. Leptin specifically stimulates GH release from normal fetal somatotrophs, substantiating the functionality of its intact receptor in the fetal pituitary. Thus, pituitary adenomas appear to revert to a fetal phenotype of leptin receptor expression.     

Temporal stability of polydipsia-hyponatremia

Among its many proposed functions, neuropeptide Y (NPY) is thought to modulate the hypothalamic-pituitary axis. Specifically, increased hypothalamic NPY signaling may be critical in mediating the neuroendocrine response to fasting. To determine the consequences of NPY deficiency on endocrine physiology, multiple hormones were quantitated in wildtype and NPY-knockout mice under fed and fasted conditions. Serum concentrations of leptin, corticosterone, thyroxine, and testosterone were normal in NPY-knockout males fed ad libitum. A 48-hour fast resulted in a 50% reduction in leptin, a 60% reduction in thyroxine, a 75% reduction in testosterone, and a 12-fold increase in corticosterone in both wildtype and NPY-knockout mice. Fasting also increased the estrous cycle length by 3 days in both wildtype and NPY-deficient female mice. We conclude that NPY is not essential for appropriate function of the gonadotropic, thyrotropic, or corticotropic axes under ad lib fed conditions or in response to acute fasting.     

Galanin in the hypothalamus of fed and fasted lean and obese Zucker rats

Galanin (GAL), a 29 aminoacid peptide, is widely distributed in the central nervous system and especially in the hypothalamus. It strongly stimulates food intake when it is injected in the paraventricular nucleus (PVN) of normal rats. The obese Zucker rat with a well-established hyperphagia is characterized by a general dysregulation of some important neuropeptides involved in the regulation of feeding behavior e.g. neurotensin, NPY or CCK and the aim of this study was to measure GAL in different microdissected brain areas in lean (Fa/Fa) and obese (fa/fa) male Zucker rats. As feeding status may modulate the central peptide concentrations, it was measured in ad libitum fed rats and in 48-h fasted rats of both genotypes. GAL was measured by a specific radioimmunoassay in the arcuate nuclei (ARC) and parvocellular (PVNp) and magnocellular (PVNm) parts of the PVN as well as in the median eminence (ME), median preoptic area (MPOA), supraoptic (SON) and dorsomedian (DMN) nuclei. Two-way analysis of variance revealed a very significant effect of genotype in the PVNp (P < 0.001), SON (P < 0.001) and in the ME (P < 0.02). No significant variations at all were noted in the ARC, PVNm, MPOA and DMN. GAL concentrations were more than doubled in the PVNp and SON of ad lib obese rats when compared to the ad lib lean rats (P < 0.005). On the other hand, in the ME where GAL concentration was about 4-fold greater than in the other areas, there was a 20 to 30% decrease in GAL concentrations in the obese rat (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)