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Biomedical subjects

H B Schiöth

Publications and source records attributed to H B Schiöth.

At least 19 recordsLinked to original sources
PubMed2005

High species variation within the repertoire of trace amine receptors.

Using a variety of search strategies, we obtained the complete or nearly complete repertoire of trace amine receptors from humans, mice, rats, zebrafish, pufferfish, and a number of invertebrates. We found that the number of functional receptors varies from 5 to 50 in each genome, showing that this family of GPCRs has a very dynamic gene repertoire. We show that the previously cloned and characterized GPCRs from insects and mollusks are more closely related to mammalian serotonin, dopamine, and adrenalin receptors than to mammalian TA receptors. This suggests that the ability to bind TAs has arisen independently in different developmental lineages.

Amino Acid Sequence↗
PubMed2005

The ancestry of the prolactin-releasing hormone precursor.

The prolactin-releasing hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.

Animals↗
PubMed2002

Food conversion is transiently affected during 4-week chronic administration of melanocortin agonist and antagonist in rats.

The central melanocortin system is involved in the regulation of food intake and body weight. In this study, we investigated the effect of a 4-week intracerebroventricular infusion of the melanocortin receptor agonist MT-II and the selective melanocortin-4 receptor antagonist HS024 on food intake and body weight homeostasis. The MT-II-treated rats ate less and lost considerably more weight than the control rats during the first week of treatment. During the second and third week, they gained weight and, by the end of the treatment period, the weight gain was similar to that of the control rats. The HS024 treatment caused hyperphagia and development of obesity during the entire period. Extensive accumulations of fat and a sixfold increase in leptin levels were observed in the HS024-treated rats, as compared with controls, after the 4-week period. Food conversion ratio, defined as body weight increase relative to weight of ingested food, was clearly increased in the HS024-treated rats, while it was lowered in the MT-II-treated rats compared with controls. The effect on food conversion ratio was transient, being greatest for both experimental groups during the first week and it was then attenuated to reach the level of controls at the end of the study. The results suggest that long-term injection of exogenous melanocortin receptor active substances may have an important transient effect on food conversion.

Analysis of Variance↗
PubMed2001

Nitric oxide mediates leptin-induced preovulatory luteinizing hormone and prolactin surges in rats.

The objective of this study was to investigate whether nitric oxide (NO) plays a significant role in mediating the facilitatory action of leptin on the reproductive system. The covariate of reproductive function we used for evaluation was preovulatory surges of luteinizing hormone (LH) and prolactin (PRL), which were simulated by priming ovariectomized rats with estradiol and progesterone. A systemic treatment of normally-fed rats with an NO synthase inhibitor (N(W)-nitro-L-arginine methyl ester) significantly decreased the magnitude of both LH and PRL surges. Three-day-fasted rats did not show a significant surge of either LH or PRL. An intracerebroventricular administration of leptin to fasted rats led to a significant recovery of these hormonal surges, but a simultaneous administration of both the NO synthase inhibitor and leptin significantly abrogated the effects of leptin. This is the first report to demonstrate a significant intermediary role of NO in leptin-induced preovulatory LH and PRL surges in rats.

Animals↗
PubMed2001

Melanocortin receptor agonist transiently increases oxygen consumption in rats.

Acute injections of melanocortin (MC) agonist and antagonist are highly effective in reducing or increasing food take, respectively. Much less is known about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the effect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this increase had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreased the food intake during the first days, but then the feeding recovered and the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, even though the weight loss was maintained. The HS024 treated rats were hyperphagic throughout the test period, continuously gaining weight, resulting in increased fat pads and high leptin levels. This is the first study that describes long term effects of MC receptor agonist and antagonist on metabolism and energy balance.

Animals↗
PubMed2001

A significant participation of orexin-A, a potent orexigenic peptide, in the preovulatory luteinizing hormone and prolactin surges in the rat.

Orexins are novel hypothalamic peptides which stimulate food intake. In view of the well-known tight connection between the nutritional state and the reproductive function, in this study we examined a possible role of orexin-A in the generation of ovarian steroid-induced luteinizing hormone (LH) and prolactin (PRL) surges in ovariectomized rats. Experiments were performed on both normally-fed and 3-day-fasted rats. Although fasting led to abolition of both LH and PRL surges, intracerebroventricular administration of orexin-A (0.3 and 3.0 nmol) resulted in a dose-dependent recovery of the hormonal surges. In addition, anti-orexin-A antisera given to normally-fed rats completely abrogated the surges of both hormones. These results demonstrate for the first time a significant participation of orexin-A in the preovulatory LH and PRL surges in the rat.

Animals↗
PubMed2001

Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat.

We previously reported that the melanocortin 4 receptor may play a significant role in mediating the preovulatory surges of luteinizing hormone and prolactin in the rat. In order to confirm this previous finding, in the present study we examined and compared the effects of intracerebroventricular administrations of 1.0 nmol of MT II (a non-selective melanocortin 3 and 4 receptor agonist) and 10 nmol of gamma(1)-melanocyte-stimulating hormone (a selective melanocortin 3 receptor agonist) on luteinizing hormone and prolactin surges in starved, gonadal steroid-primed ovariectomized female rats, which is a model deprived of inherent surges of the two hormones. MT II significantly recovered the surge of prolactin, but not of luteinizing hormone (although a tendency to increase was seen), and gamma(1)-melanocyte-stimulating hormone was without effect on both hormones. This study corroborated our previous report through a different and direct approach that the melanocortin 4 receptor, but not the melanocortin 3 receptor, plays a significant role in mediating the preovulatory prolactin surge in the rat.

Animals↗
PubMed2001

Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats.

In order to examine a possible detrimental effect of hyperleptinemia on the reproductive system, we examined whether a decrease in circulating leptin levels by fasting affects the estradiol/progesterone-induced luteinizing hormone (LH) and prolactin (PRL) surges in genetically obese OLETF (Otsuka-Long-Evans-Tokushima-Fatty) rats. Experiments were performed on both normally fed and 3-day starved groups from ovariectomized OLETF rats and their controls LETO (Long-Evans-Tokushima-Otsuka). Starved LETO rats, whose leptin levels were less than 0.5 ng/ml, did not show a significant surge of either LH or PRL. Normally fed OLETF rats, whose leptin levels were 9.7 +/- 1.8 ng/ml, showed a significant but small surge for both LH and PRL. Interestingly, starved OLETF rats, whose leptin levels (4.1 +/- 0.7 ng/ml) were similar to those in normally fed LETO rats (3.3 +/- 0.4 ng/ml), had significantly greater surges of both hormones than normally fed OLETF group. This study demonstrates for the first time that the normalization of circulating leptin levels in female OLETF rats augments the steroid-induced LH and PRL surges, and also suggests a deleterious effect of hyperleptinemia on the reproductive axis.

Animals↗
PubMed2000

Stimulation of prolactin secretion by chronic, but not acute, administration of leptin in the rat.

Leptin, the product of obese (ob) gene, has been reported to affect the secretion of all six anterior pituitary hormones, but data are especially scarce regarding the interplay between leptin and prolactin (PRL). Thus, in this study we examined and compared in vivo the effects of acute and chronic administrations of recombinant mouse leptin on PRL secretion in male rats. Normally-fed and 3-day-fasted rats received an intraperitoneal bolus injection of leptin [1.0 mg/kg body weight (BW)] or vehicle only. The leptin treatment was without effect on plasma PRL levels up to 5 h postadministration. Food deprivation for 3 days significantly decreased both PRL and leptin levels. This decrease in plasma PRL was prevented by a 3-day constant infusion of 75 microg/kg BW/day of leptin, which maintained plasma leptin levels similar to those of normally-fed rats. The administration of three times the higher dose of leptin (225 microg/kg BW/day) to fasted rats led to further increases in both PRL and leptin in the plasma. Thus, a dose-dependent stimulatory effect of chronic leptin treatment on PRL secretion was indicated. This study demonstrates that chronic, but not acute, administration of leptin stimulates PRL secretion in the rat.

Animals↗
PubMed2000

Tonic inhibition of food intake during inactive phase is reversed by the injection of the melanocortin receptor antagonist into the paraventricular nucleus of the hypothalamus and central amygdala of the rat.

Melanocortins inhibit food intake and melanocortin 4 receptor (MC(4)R) antagonists stimulate feeding behaviour. These effects may occur due to stimulation or blockade of MC(4) receptors in the hypothalamus. To test the validity of this hypothesis, a cyclic peptide, the MC(4)R selective antagonist HS014 (20, 100 and 500 pmol), or vehicle, was injected unilaterally into the paraventricular nucleus of the hypothalamus (PVN). As MC receptors are expressed also in extrahypothalamic sites involved in the regulation of feeding behaviour, HS014 was injected bilaterally into the vicinity of the central nucleus of the amygdala (CA) and the nucleus accumbens region (Acc). All doses of HS014 induced a dose-dependent increase in food intake when injected into the PVN. Intra-amygdalar injections of HS014 (50 and 250 pmol/side) also stimulated food intake, whereas a 10-pmol dose was inactive. Local microinjections of HS014 into the Acc failed to stimulate feeding. These data suggest that endogenous melanocortin receptor agonists exert a tonic inhibitory influence on food consumption by stimulating MC(4) receptors in the hypothalamus and amygdala.

Amygdala↗
PubMed2000

Involvement of prolactin-releasing peptide in the preovulatory luteinizing hormone and prolactin surges in the rat.

Prolactin (PRL)-releasing peptide (PrRP) is a novel hypothalamic peptide reported as a potent and specific stimulator of PRL secretion. In this study, we examined a possible role of PrRP in the ovarian steroid-induced PRL surge in the rat, simultaneously observing the change in luteinizing hormone (LH) surge. Experiments were performed on both normally-fed and three-day-fasted rats, which were ovariectomized and primed with estradiol and progesterone. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. All the following substances were given intracerebroventricularly at 11:00 h. Compared to control serum, anti-rat PrRP31 serum caused a significant reduction of the LH and PRL surges. The antiserum also delayed the onset of PRL surge. Fasted rats were devoid of significant surges of the hormones, while 3.0, but not 0.5 nmol of rat PrRP31 given to these animals produced a significant recovery of PRL surge. Although LH surge was not reinstated, basal LH secretion was transiently stimulated by 3.0 nmol of PrRP31. These results demonstrate for the first time a significant participation of PrRP in the preovulatory LH and PRL surges in the rat. Possible indirect pathways mediating this effect of PrRP were discussed, in view of the unique anatomical distribution of PrRP in the hypothalamus.

Animals↗
PubMed2000

Evaluation of the role for prolactin-releasing peptide in prolactin secretion induced by ether stress and suckling in the rat: comparison with vasoactive intestinal peptide.

Prolactin (PRL)-releasing peptide (PrRP) is a recently discovered hypothalamic peptide possessing a specific stimulatory action on PRL secretion. In this study, we examined whether PrRP plays a role in mediating ether stress- and suckling-induced PRL secretion in rats through administering anti-PrRP antisera intracerebroventricularly. For comparison, we also tested the effect of anti-vasoactive intestinal peptide (VIP) antisera on the hormonal responses, since VIP is another candidate for a physiological PRL-releasing factor. The immunoneutralization of VIP, but not of PrRP, led to a significant suppression of PRL responses to both ether and suckling. These results suggest that PrRP may not play a significant role, or at least play a much weaker role than VIP, in mediating PRL release induced by ether stress and suckling in the rat.

Animals↗
PubMed2000

Differential effects of melanocortin peptides on ingestive behaviour in rats: evidence against the involvement of MC(3) receptor in the regulation of food intake.

The pro-opiomelanocortin-derived peptides decrease food intake possibly via MC4 receptor. In this study we compared the effects of alpha-melanocyte-stimulating hormone (MSH), beta-MSH and gamma(1)-MSH (0.2, 1.0 and 5.0 microg, i.c.v.) on food intake. alpha-MSH and beta-MSH inhibited spontaneous food intake in a dose dependent manner, whereas the gamma(1)-MSH did not. alpha-MSH and beta-MSH but not gamma(1)-MSH (all 5.0 microg, i.c.v.) inhibited fasting-induced food intake about 50%. None of the three peptides inhibited fluid consumption in water-deprived (24 h) rats. It is suggested that MC(3) receptor, activated selectively by gamma(1)-MSH, is not involved in the regulation of food intake.

Animals↗
PubMed2000

ACTH- and alpha-MSH-induced grooming, stretching, yawning and penile erection in male rats: site of action in the brain and role of melanocortin receptors.

The effect of adrenocorticotropin (ACTH)(1-24) and alpha-melanocyte stimulating hormone (alpha-MSH) on grooming, stretching, yawning and penile erection was studied after injection into different brain areas. Both peptides induce the above responses when injected into the hypothalamic periventricular region of the third ventricle. This region includes the paraventricular nucleus, the dorsomedial nucleus, the ventromedial nucleus and the anterior hypothalamic area. The minimal effective dose of both peptides was 0.5 microg and the maximal effect was seen with 2 microg, the highest dose tested. Irrespective of the injection site, grooming started 5-7 min after injection of either peptide, while stretching, yawning and penile erection started only after 15-35 min and lasted for 90-120 min. In contrast both peptides were ineffective when injected into the preoptic area, the caudate nucleus or the CA1 field of the hippocampus. Grooming, stretching and yawning, but not penile erection, were prevented by cyclic[AcCys(11), D-Nal(14), Cys(18), AspNH(2)(22)]-beta-MSH (11-22) (HS014), a selective melanocortin 4 receptor antagonist, injected into the same periventricular area 10 min before of ACTH(1-24) or alpha-MSH. The results show that ACTH(1-24) and alpha-MSH act in the hypothalamic periventricular region to induce the above responses and that grooming, stretching and yawning, but not penile erection, are mediated by melanocortin 4 receptors.

Animals↗
PubMed2000

Anorexigenic cocaine- and amphetamine-regulated transcript peptide intensifies fear reactions in rats.

An increasing number of appetite-regulating peptides are being discovered. The list of regulators inhibiting food intake is considerably longer than that of appetite stimulators. In many cases, the peptides inhibiting food intake facilitate fear reactions, whereas the majority of the agents reducing anxiety responses stimulate appetite. Cocaine- and amphetamine-regulated transcript (CART) cDNA was isolated from hypothalamic libraries and CART was reported to inhibit food intake and to mediate the anorectic effects of leptin. Here, we show that the active core fragment of CART (CART(89-103), 0.04-5.0 nmol) injected into lateral cerebral ventricle not only inhibits food intake, but also causes a dose-dependent increase in anxiety-like reactions in elevated plus-maze test. Intracerebroventricular administration of CART(82-103) (0.04-5.0 nmol) did not inhibit water intake and did not affect spontaneous locomotor activity in the open field test ruling out unspecific effects of the peptide. Our results suggest that CART could be an endogenous factor in the brain mediating the effects of stress on appetite.

Animals↗
PubMed2000

Downregulation of melanocortin receptors in brain areas involved in food intake and reward mechanisms in obese (OLETF) rats.

The melanocortin (MC)4 receptor is important for food intake and weight homeostasis as it mediates the orexigenic and anorexigenic effects of the MCs. OLETF (Otsuka-Long-Evans-Tokushima-Fatty) rats are a selective inbred strain of polygenic variant rats which overeat and develop obesity with elevated leptin levels. We investigated by autoradiography if the expression of MC receptors were altered in ovariectomized estradiol-replaced female OLETF rats compared to their controls (Long-Evans-Tokushima-Otsuka (LETO) rats). We found that OLETF rats show a reduction in total [125I]NDP-MSH MC receptor binding in the ventromedial hypothalamic nucleus, perhaps reflecting an increased release of MC peptides in this region. The levels of MC receptors in the arcuate nucleus and the paraventricular hypothalamic nucleus were not changed. Interestingly, the OLETF rats also showed reduced MC-receptor binding in areas such as the nucleus accumbens shell, and the ventral tegmental area, both of which are believed to be involved in reward systems. Similarities in the changes of MC receptor expression in obese animals and in animals treated with opiates may suggest a neurobiological link between food intake mediated through the MC receptors and reward.

Animals↗
PubMed2000

Melanocortins and feeding behavior.

The melanocortin (ACTH/MSH) peptides exert a number of central effects. In the eighties, we described for the first time a role for melanocortins in the central control of appetite. We showed that the injection of ACTH-(1-24) into a brain lateral ventricle reduced food intake up to 76.6% in starved rats. Injections into the ventromedial hypothalamus during the nocturnal feeding phase also markedly inhibited food intake. These effects were also confirmed in mice and rabbits. Targeted disruption of the MC4 receptor resulting in obesity in mice explained the role of this receptor in mediating effects of melanocortins on food intake. Administration of MC4 receptor agonists leads to acute reduction in food intake and body weight, while the reverse effects are observed after administration of selective MC4 receptor antagonists, confirming the role of the melanocortins in mediating a tonic inhibition on feeding behavior. Moreover, immobilization stress-induced anorexia may be partially reversed by single and repeated intracerebroventricular administration of selective MC4 receptor antagonists. It is thus evident that MC4 receptor blockage can reduce stress-induced anorexia and that repeated injections of selective MC4 receptor antagonists have a sustained effect on food intake without any sign of tachyphylaxis. However, we have also shown that the behavioral effects of CRF (anorexia and grooming) are not influenced by MC4 receptor blockage. These effects of CRF are thus not due to an indirect mechanism caused by an increased release of melanocortins acting on the central MC receptors.

Adrenocorticotropic Hormone↗