Does neuropeptide Y contribute to the anorectic action of amylin?

Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.     

Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats

Oxyntomodulin (OXM) is a product of proglucagon processing in the intestine and the central nervous system. We reported that intracerebroventricular (ICV) and intranuclear administration of OXM caused an inhibition of food intake in rats (Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, and Bloom SR. Endocrinology 142: 4244-4250, 2001). In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmol, for 7 days. A pair-fed control was included. These animals were restricted to the food intake of the OXM group but injected twice daily with saline. OXM-treated animals gained significantly less weight than either control group (day 8: OXM, 12.2 +/- 1.9 g vs. pair fed, 21.0 +/- 2.1 g; P < 0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13 +/- 0.03 g vs. pair fed, 1.29 +/- 0.04 g; P < 0.05) and interscapular brown adipose tissue (OXM, 0.15 +/- 0.01 g vs. pair fed, 0.18 +/- 0.01 g; P < 0.05) and increased core temperature compared with saline control, suggestive of enhanced energy expenditure. The food restriction-induced suppression in plasma TSH, seen in the pair-fed group, was prevented by OXM, potentially via increased release of hypothalamic TRH. In summary, ICV OXM causes reduced body weight gain and body adiposity following chronic administration.     

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats

The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4+/-0.1 g (vehicle) vs 1.6+/-0.5 g (180 pmol H3), 2.4+/-0.5 g (540 pmol H3) and 2.2+/-0.5 g (1,620 pmol H3), p<0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8+/-7.1 g (vehicle) vs 261.6+/-6.7 g (ad libitum fed H3), p<0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake.     

Influence of neuropeptide Y (NPY) on food intake and growth of penaeid shrimps Marsupenaeus japonicus and Penaeus semisulcatus (Decapoda: Penaeidae)

The effects of neuropeptide Y (NPY) administered intramuscularly or orally on postlarvae (PLs) of two penaeid species were investigated in this study. In experiment 1, food intake (FI) of Marsupenaeus japonicus PLs (0.96 g), injected with NPY at 0.6 microg per g BW, was investigated within 48 h posttreatment. In experiment 2, oral administration of NPY (at doses of 0, 0.125, 0.25, 0.5 microg g(-1) food) on feed intake and growth performance of Penaeus semisulcatus PLs (0.27 g) was examined for 6 weeks. In experiment 1, NPY injection significantly increased average daily FI of M. japonicus PLs within the first 24 h compared to the control (P<0.05), but its stimulatory effect decreased on the second day (P>0.05). The increase in FI was 33% during the first 24 h and 17% during the next 24 h. In experiment 2, significant (P<0.05) differences were found among the groups in terms of weight gain and food utilization (P<0.05). Mean FI significantly increased (as much as 1.3-fold over the control) when NPY was orally administered at doses from 0.125 to 0.5 microg g(-1) feed. There was a positive relationship between FI and final weight (y=-0.972+2.098x, R(2)=0.81) and between FCE and NPY doses in the diets (y=45.37+3.46x, R(2)=0.91). The present findings indicated for the first time that NPY is a potent stimulator of food intake when administered either intramuscularly or orally to penaeid shrimps.     

Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.

For this study, we have determined the effects of neonatal leptin treatment on the evolution of body weight. Experiment 1: pups were divided into two groups: LepF - injected with leptin (8 micro g/100 g of body weight) for the first 10 days of lactation and control (C) - receiving saline. Experiment 2: pups were divided into two groups: LepL - injected with the same leptin concentration of experiment one for the last 10 days of lactation, and C, which received saline. Body weight and food intake were monitored until age 150 days, after which leptin concentrations were measured by ELISA. The LepF group had a significant increase in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day 74 onward, and higher serum leptin concentration compared to the control (108 %, p < 0.05). The LepL group had a significant increase in body weight (p < 0.05) from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher serum leptin concentration compared to controls (6.9 %, p < 0.05). These results suggest that both periods of lactation constituted a critical window for body weight and food intake programming, but the effects are more marked when the leptin is injected within the first ten days.     

Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces no effect or a transient reduction in daily food intake and body weight. Our aim was to identify an intermittent dosing strategy for intraperitoneal infusion of salmon calcitonin (sCT), a homolog of amylin that produces a sustained 25-35% reduction in daily food intake and adiposity in diet-induced obese rats. Rats (649 +/- 10 g body wt, 27 +/- 1% body fat), with intraperitoneal catheters tethered to infusion swivels, had free access to a 45% fat diet. Food intake, body weight, and adiposity during the 7-wk test period were relatively stable in the vehicle-treated rats (n = 16). None of 10 sCT dosing regimens administered in succession to a second group of rats (n = 18) produced a sustained 25-35% reduction in daily food intake for >5 days, although body weight and adiposity were reduced by 9% (587 +/- 12 vs. 651 +/- 14 g) and 22% (20.6 +/- 1.2 vs. 26.5 +/- 1.1%), respectively, across the 7-wk period. The declining inhibitory effect of sCT on daily food intake with the 6-h interinfusion interval appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of sCT on daily food intake with the 2- to 3-h interinfusion interval suggested possible receptor downregulation and tolerance to frequent sCT administration; however, food intake increased dramatically when sCT was discontinued for 1 day after apparent loss of treatment efficacy. Together, these results demonstrate the activation of a potent homeostatic response to increase food intake when sCT reduces food intake and energy reserves in diet-induced obese rats.     

Chronic leptin administration promotes lipid utilization until fat mass is greatly reduced and preserves lean mass of normal female rats

Leptin is a hormone synthesized and secreted from adipose tissue. To study the physiologic effects of chronic leptin treatment, normal adult female Sprague-Dawley rats were injected subcutaneously for 35 days. Twice daily injections (250 microgram/day, b.i.d.) resulted in a significant (P<0.05) decrease in food intake that was maintained for 10 days before gradually returning to control level by day 21. Leptin decreased body weight by a maximum of 12% of the initial body weight on day 22 and remained reduced for the duration of the treatment. After 35 days of treatment, visible peritoneal adipose tissue was not detected. Body composition analysis showed that chronic injection of leptin resulted in a dramatic decrease in fat content (28+/-2 to 4+/-2 g, P<0.05; mean+/-SEM) while the lean content remained unchanged. Rats pair-fed to the leptin-treated group but treated with vehicle had the same body composition (23+/-3 g fat mass) as that measured for the ad libitum fed controls. Using indirect calorimetry we observed that leptin decreased respiratory quotient and thus increased fat oxidation. Leptin also prevented energy expenditure reduction typically associated with food restriction. Leptin treatment for 35 days decreased plasma triglyceride (0.75+/-0.07 to 0.30+/-0.03 mM, P<0.05), free fatty acid (0.56+/-0.06 to 0.32+/-0.04 mM) and insulin (3.2+/-0.5 to 1. 4+/-0.4 ng/ml, P<0.05) concentrations despite the fact that food intake was normalized by day 35. Withdrawal of leptin triggered hyperphagia indicating that leptin biology remained throughout the duration of the chronic treatment. These data suggest that leptin reduces fat mass by initially decreasing appetite and by maintaining enhanced fat utilization even when food intake has returned to that of vehicle-treated control.     

Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.     

Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats.

Neuropeptide Y (NPY) is a powerful appetite stimulant, and hypothalamic concentrations rise after food deprivation and in experimental diabetes. Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin in chow-fed rats and in rats with dietary obesity, and examined the effect of dexfenfluramine on these peptides in this model. Sixty-five rats were fed a palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs. 113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or 28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay. Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was significantly higher in the palatable diet group compared to chow-fed controls (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than 0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at reducing weight gain in the animals fed the palatable diet, this did not result in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be of importance in diet-induced obesity but the weight loss produced by dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.     

Photoperiodic variation of Leydig cell numbers in the testis of the golden hamster: a possible mechanism for their renewal during recrudescence

Golden hamster testes regress after short day exposure. The present study asks: 1) are Leydig cell numbers depleted during short days, and 2) if so, how are they replenished during recrudescence. Control hamsters were shown 14 h of light and 10 h of dark (LD 14:10) for 10 weeks (n = 12). Testicular regression was induced by LD 6:18 for 10 weeks (n = 4), and recrudescence by switching regressed hamsters to LD 14:10 for 3 and 5 weeks (n = 8 for each group). All hamsters were injected with [3H]thymidine [3 microCi/gm body wt., intraperitoneally (i.p.)] 1 h or 2 weeks before sacrifice. Leydig cell number per testis was determined by stereological analysis of sections of perfusion-fixed testes, and labeling indices were determined by autoradiography. Leydig cell numbers were reduced significantly from 18.2 X 10(6) in control to 9.0 X 10(6) in regressed testes (p less than 0.05); then increased to 14.0 X 10(6) and 17.9 X 10(6) in 3- and 5-week recrudesced hamsters. The labeling index was nondetectable (n.d.) for regressed hamsters. In control and recrudescing hamsters the labeling index was measured at two times (t1 = 1 h vs. t2 = 2 weeks post-injection): in controls, t1 = 0.22 +/- 0.15% (mean +/- SEM) vs. t2 = 0.28 +/- 0.22%; in 1 week recrudesced, n.d. vs. 1.92 +/- 0.77% (p less than 0.05); at 3 wk, n.d. vs. 4.58 +/- 1.74% (p less than 0.05); at 5 weeks, 1.92 +/- 0.61% vs. 2.25 +/- 0.59%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice

Exposure to high-fat diets for prolonged periods results in positive energy balance and obesity, but little is known about the initial physiological and neuroendocrine response of obesity-susceptible strains to high-fat feeding. To assess responses of C57BL/6J mice to high- and low-fat diets, we quantitated the hypothalamic expression of neuropeptides implicated in weight regulation and neuroendocrine function over a 2-wk period. Exposure to high-fat diet increased food consumption over a 2-day period during which leptin levels were increased when assessed by a frequent sampling protocol [area under the curve (AUC): 134.6 +/- 10.3 vs. 100 +/- 12.3, P = 0.03 during first day and 126.5 +/- 8.2 vs. 100 +/- 5.2, P = 0.02 during second day]. During this period, hypothalamic expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased by approximately 30 and 50%, respectively (P < 0.001). After 1 wk, both caloric intake and hypothalamic expression of NPY and AgRP returned toward baseline. After 2 wk, cumulative caloric intake was again higher in the high-fat group, and now proopiomelanocortin (POMC) was elevated by 76% (P = 0.01). This study demonstrates that high-fat feeding induces hyperphagia, hyperleptinemia, and transient suppression of orexigenic neuropeptides during the first 2 days of diet. The subsequent induction of POMC may be a second defense against obesity. Attempts to understand the hypothalamic response to high-fat feeding must examine the changes as they develop over time.     

Intracerebroventricular injection of proinsulin C-peptide does not influence food consumption in male Long-Evans rats.

Insulin and C-peptide are released in equimolecular concentrations in the circulation after food ingestion as they result from the enzymatic cleavage of proinsulin. In the brain, insulin inhibits food intake through hypothalamic receptors. In the present study, we tested the ability of C-peptide to modulate food intake when injected in the brain lateral ventricle of Long-Evans rats. For this purpose, 10 adult male rats (BW 320 - 350 g) were deprived of food overnight. They were intra-cerebroventricularly injected with 10 microg C-pepitde or vehicle (artificial cerebrospinal fluid [CSF]) during the first hour of the light period and chow intake was measured 1, 3, 6 and 24 hours after injection. Chow availability immediately triggered food consumption. Food intake was not different between CSF- and C-peptide-injected rats either after one hour (5.7 +/- 0.6 g [CSF] vs. 6.7 g +/- 0.5 g; ns) or after 24 hrs (23.3 +/- 1.4 g [CSF] vs. 25.1 g +/- 1.4 g; ns). In addition, a higher dose (20 microg/rat) had no effect at all in satiated rats one hour after injection or later contrary to the 100 % increase measured after injection of 2 microg of neuropeptide Y. Thus, we conclude that contrary to insulin, C-peptide does not regulate feeding behaviour in normal rats whatever their insulin status.     

Hypothalamic hypocretin/orexin and neuropeptide Y: divergent interaction with energy depletion and leptin

The aim of this study was to measure the effects of chronic leptin treatment on two orexigenic peptides present in the hypothalamus namely hypocretin/orexin and neuropeptide Y (NPY). For this purpose, recombinant murine leptin (0.2 mg/rat/day) or saline were injected intraperitoneally in Long-Evans rats for 7 consecutive days. Food intake (-8%; p < 0.002) and body weight gain (23.7 +/- 1 vs 31.5 +/- 1.3 g; p < 0.003) were significantly lower in leptin-treated rats than the saline-treated rats. NPY concentrations did not change significantly in any of the microdissected brain areas including the arcuate and paraventricular nuclei. Orexin A concentration in the lateral hypothalamus was significantly decreased by the leptin treatment (-68%; p < 0.01). A smaller decrease (-46%; p < 0.04) was also noted in saline-treated rats pairfed to the level of the leptin-treated rats. We conclude that orexin/hypocretin could be considered as a new relay for leptin in the central nervous system. Its variation in case of lower energy supply observed in pairfed rats could constitute an alerting system for the brain and therefore considered as the first step in the establishment of defense mechanisms against energy depletion.     

Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats

Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake when administered by intravenous infusion to lean and obese humans and rats. However, chronic administration of PYY(3-36) by osmotic minipump to lean and obese rodents produces only a transient reduction in daily food intake and weight gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36) every other hour for 10 days produced a sustained reduction in daily food intake, body weight, and adiposity in lean rats. Here, we determined whether intermittent delivery of PYY(3-36) can produce a similar response in diet-induced obese rats. During a 21-day period, obese rats (body fat >25%) received twice daily intraperitoneal infusion of vehicle (n = 18) or PYY(3-36) (n = 24) during hours 1-3 and 7-9 of the dark period. Rats had free access to both a 45% fat solid diet and a 29% fat liquid diet; intakes were determined from continuous computer recording of changes in food container weights. To sustain a 15-25% reduction in daily caloric intake, the initial PYY(3-36) dose of 30 pmol.kg(-1).min(-1) was reduced to 10 pmol.kg(-1).min(-1) on day 10 and then increased to 17 pmol.kg(-1).min(-1) on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11-32% and prevented body weight gain (8 +/- 6 vs. 51 +/- 11 g) and fat deposition (4.4 +/- 7.6 vs. 41.0 +/- 12.8 g). These results indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a sustained reduction in food intake and adiposity in diet-induced obese rodents consuming palatable high-fat foods.     

Effect of prolonged glucose infusion into fetal sheep on body growth, fat deposition and gestation length

Eleven Merino sheep fetuses were supplemented with glucose by direct continuous intravenous infusion of 50% dextrose into the fetus from day 115 of gestation until spontaneous delivery. Infusion rates of 15 or 25 g/day per kg were used and equivalent volumes of saline were infused into 11 control fetuses. Infusion periods approximated 27 days in both groups. Fetal plasma glucose concentrations were significantly (P less than 0.001) elevated throughout glucose infusion and resulted in variable but consistently higher plasma insulin concentrations in the glucose than in the saline-infused fetuses. Glucose-infused fetuses were significantly heavier than controls (mean +/- SEM; 3.86 +/- 0.16 vs 3.28 +/- 0.24 kg, P less than 0.05) and body fat depots (in g/kg body wt.) were larger in glucose-infused than control fetuses (9.91 +/- 0.65 vs 6.73 +/- 0.37, P less than 0.005, for internal brown fat depots; 1.25 +/- 0.44 vs 0.27 + 0.13, P less than 0.05, for subcutaneous white adipose tissue). The results indicate that growth and lipid deposition in the sheep fetus are responsive to increased glucose supply, an effect which may be mediated through the actions of insulin. Mean gestation length was 146.60 +/- 1.45 days for controls and 144.18 +/- 1.23 days for glucose-infused animals (normal term 150 days).     

Pertussis toxin inhibits neuropeptide Y-induced feeding in rats

Neuropeptide Y (NPY) is the most powerful peptide drug stimulating feeding in rats. Rats with paraventricular hypothalamic (PVH) cannulae were used to investigate the mechanisms involved in NPY-induced feeding. Consistent with previous reports, injection of 2 μg of NPY into the PVH significantly increased the cumulative food intake over 1-, 2- and 4-hr periods. Ad lib feeding decreased significantly two days after pertussis toxin (PT) administration, but recovered to nearly normal levels on the fourth day. PT had no immediate effect on NPY-induced feeding; however, four days after PT was injected NPY (2 μg) did not increase the food intake compared to control. In vitro investigations showed that isoproterenol-stimulated adenylate cyclase activity in the hypothalamus of control rats was inhibited by NPY. In PT-treated rats, however, no inhibition of cAMP production was observed. These results suggest that cAMP may mediate NPY-induced feeding and that a PT-sensitive G protein may be involved in this signal transduction.     

Neuropeptide Y chronically injected into the hypothalamus: A powerful neurochemical inducer of hyperphagia and obesity

Neuropeptide Y (NPY), a putative neurotransmitter abundant in the brain, has recently been shown to act within the hypothalamus, inducing a powerful eating response and a specific appetite for carbohydrates. In the present study, NPY (235 pmol) injected bilaterally in the paraventricular nucleus three times a day for 10 days caused approximately a two-fold increase in daily food intake, a six-fold increase in the rate of body weight gain and a three-fold increase in the body fat of female rats. Subsequently, the food intake and body weight of these subjects decreased precipitously, reaching control levels 20 days postinjection. These findings, demonstrating that exogenous NPY is capable of overriding mechanisms of satiety and body weight control, suggest that disturbances in NPY function may play a role in some disorders of eating behavior and body weight regulation.     

Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus

Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY(1-36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20 microliters/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 micrograms/min. Two perfusions of 1.0 micrograms/min NPY evoked an intake of 4.6 +/- 1.1 g of food over a 3.0-h period, whereas 4-7 and 8-15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0 +/- 1.1 g and 33.2 +/- 3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0 micrograms/min NPY caused a cumulative intake of food in the rats of 14.2 +/- 2.0 g and 31.7 +/- 3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired LH-RH release by estrogen in women with sulpiride-induced hyperprolactinemia

The effects of hyperprolactinemia on the release of immunoreactive luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH) in response to iv injection of 20 mg conjugated estrogens (Premarin) were studied. Five normal cycling women were injected with Premarin on the morning of the 7th day of the first cycle (control cycle), and then the plasma levels of LH-RH, LH, and prolactin (PRL) were determined every 8 to 16 hours for 72 h. Two months later, the same women received 200 mg of oral sulpiride daily for 8 days from the 3rd day of the cycle (sulpiride treated cycle), and then the same protocol as in the control cycle was applied. Mean (+/- SE) plasma levels of PRL on day 7 in the sulpiride treated cycle were significantly higher than those in the control cycle (118 +/- 24 ng/ml vs. 14 +/- 4 ng/ml, p less than 0.001). After estrogen injection, the mean percent increases in immunoreactive LH-RH at 32 h (control: 71 +/- 38% vs. sulpiride: 6 +/- 36%) and 40 h (154 +/- 38% vs. -5 +/- 21%) and in LH at the 48 h (175 +/- 89% vs. 57 +/- 57%) and 56 h (99 +/- 32% vs. 7 +/- 21%) were significantly (p less than 0.01 or p less than 0.05) suppressed in the sulpiride cycle. These data suggest that the impaired positive feedback effect of estrogen on LH-release in hyperprolactinemic anovulatory women may be caused, at least in part, by disturbed LH-RH release.