Evidence of a physiological role for neuropeptide Y in ventromedial hypothalamic lesion-induced hyperphagia.

We evaluated the role of neuropeptide Y (NPY), a potent endogenous orexigenic signal, in the ventromedial hypothalamic (VMH) lesion-induced hyperphagia in rats. To produce hyperphagia and excessive weight gain, adult female rats received bilateral electrolytic or sham lesions in the VMH. Concurrently, a permanent intracerebroventricular cannula was implanted in the third ventricle of the brain.

In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals.

Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasing hormone release in vitro.

Agmatine, a clonidine displacing substance and imidazoline receptor agonist, was recently isolated from bovine brain and shown to be present in the rat hypothalamus. Since clonidine can stimulate the release of pituitary luteinizing hormone (LH), we tested the hypothesis that agmatine may similarly act in the rat to stimulate the hypothalamic luteinizing hormone-releasing hormone (LHRH)-pituitary LH axis. Administration of agmatine intracerebroventricularly rapidly augmented the release of LH in a dose-related fashion in ovariectomized, ovarian steroid-primed rats.

The effects of interleukin 1 beta on the hypothalamic tachykinin, neurokinin A.

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that appears to be an integral component of the bidirectional signalling between the immune and central nervous systems. It is produced in the hypothalamus and has been shown to inhibit the hypothalamo-pituitary-gonadal axis and to activate the hypothalamo-pituitary-adrenal axis. IL-1 beta is reported to up-regulate the tachykinin, substance P (SP), in the peripheral nervous system.

Evidence in support of nitric oxide (NO) involvement in the cyclic release of prolactin and LH surges.

Studies were undertaken to determine whether nitric oxide (NO) is involved in induction of the prolactin surge on proestrus and in that induced by ovarian steroids in ovariectomized (ovx) rats, by using inhibitors of NO synthase, the enzyme that generates NO. Two week-ovariectomized rats were treated either with estradiol benzoate (EB, 30 micrograms/rat, s.c.

The hypothalamic peptides, beta-endorphin, neuropeptide K and interleukin-1 beta, and the opiate morphine, enhance the excitatory amino acid-induced LH release under the influence of gonadal steroids.

Several hypothalamic neuropeptides and amino acids are known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not known. In this study, we have evaluated the interaction between neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.

Naloxone reduces the feeding evoked by intracerebroventricular galanin injection.

Central injection of galanin elicits feeding in satiated rats. We recently observed galanin-immunoreactive fibers in synaptic connection with a population of beta-endorphin-immunopositive cell bodies and dendrites in the basal hypothalamus. Because beta-endorphin also stimulates food intake, these morphological findings raised the possibility that stimulation of feeding by galanin may, in part, be mediated by beta-endorphin release.

Facilitatory effects of testosterone on hypothalamic tachykinin levels and release.

We have reported earlier that central administration of tachykinins profoundly altered the release of pituitary LH and the direction of the LH response was modulated by gonadal steroids in male rats. To further understand the relationship between androgens and hypothalamic tachykinins, we have examined the effects of castration and of testosterone (T)-replacement on levels of Neurokinin A-like immunoreactivity (NKA-li) in microdissected regions of the rat hypothalamus and on in vitro release of hypothalamic NKA-li. Results showed that castration decreased NKA-li levels specifically in the median eminence (ME) and arcuate (ARC) regions as compared to those in intact rats.

Anorectic effects of estrogen may be mediated by decreased neuropeptide-Y release in the hypothalamic paraventricular nucleus.

There is a considerable body of evidence to suggest that estrogen suppresses food intake and body weight gain by an action in the hypothalamus. However, the neurotransmitter/neuromodulator mediating the anorectic effects of estrogen are unknown. Neuropeptide-Y (NPY) is the most potent orexigenic signal known, and NPY-producing neurons in the hypothalamus concentrate 17 beta-estradiol (E2).

Evidence that neuropeptide Y is a physiological signal for normal food intake.

Neuropeptide Y is the most potent orexigenic signal known. To test the hypothesis that NPY is a physiological messenger molecule for normal food intake in rats, we studied the effects of passive immunization against endogenous NPY on cumulative daily food intake in non-fasted spontaneously feeding rats. The results show that continuous central infusion of NPY antibodies markedly suppressed the nighttime and the cumulative 24 h food intake in a dose-dependent fashion.

Role of multiple voltage-sensitive calcium channels in depolarization-induced release of neuropeptide y and luteinizing hormone-releasing hormone from rat median eminence-arcuate nucleus.

The objective of the present studies was to identify the subtypes of voltage-sensitive Ca(2+) channels (VSCC) that regulate the basal and depolarization-induced release of neuropeptide Y (NPY) and LH-releasing hormone (LHRH) from rat hypothalamus. Tissues containing median eminence-arcuate nucleus (ME-ARC) were dissected from male rats and incubated in vitro in the presence and absence of agents selectively affecting N- or L-type VSCC. KCl depolarization-induced release of NPY, but not basal release, was abolished by Ca(2+)-free/EGTA medium and was significantly reduced by cobalt.

Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge: involvement of excitatory amino acids.

The involvement of excitatory N-methyl-D-aspartate (NMDA) receptors in the hypothalamic control of pituitary LH secretion is well recognized. Recent evidence shows that nitric oxide (NO), a free radical gas, may act as neurotransmitter in the brain, and its efflux is stimulated by activation of NMDA receptors. Studies were undertaken to determine whether NO is involved in the hypothalamic release of LHRH and in the LH surge induced by progesterone (P) in estrogen-primed ovariectomized rats.

Evidence that luteinizing hormone suppression in response to inhibitory neuropeptides, beta-endorphin, interleukin-1 beta, and neuropeptide-K, may involve excitatory amino acids.

A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling.

Mode of action of interleukin-1 in suppression of pituitary LH release in castrated male rats.

These studies were undertaken to elucidate the mechanisms whereby the cytokine, Interleukin (IL-1) suppresses pituitary LH release in orchidectomized rats. Since LH secretion is pulsatile in castrated rats, the effects of IL-1 on the components of the LH pulsatility were assessed. Intracerebroventricular (i.

Neuropeptide K stimulates corticosterone release in the rat.

We have investigated the effects of the tachykinin, neurokinin A (NKA) and N-terminally extended forms NPK and NP gamma on plasma levels of corticosterone. Both peripheral and central injections of these three NK-2 receptor agonists stimulated adrenal corticosterone release in gonad-intact and castrated male rats. A comparison of their effects revealed that NPK was relatively more potent than NKA and NP gamma.

Ageing of the neuropeptidergic signals in rats.

With advancing age, subtle and progressive disintegration of several components of peptidergic signals that drive luteinizing-hormone-releasing hormone (LHRH) secretion contribute to diminished pituitary-gonadal function in both sexes of the rat. The results show that in female rats, ageing per se and unopposed exposure to oestrogen disrupt different loci in the transmission line to neurones that release LHRH. Ageing per se appears to abolish the restraint on the influence of inhibitory opioids induced by a neural clock--an event necessary for the preovulatory surge of luteinizing hormone to occur in young rats.

Effect of d-fenfluramine on neuropeptide Y concentration and release in the paraventricular nucleus of food-deprived rats.

Recent evidence indicates that Neuropeptide Y (NPY) is an important signal in the hypothalamic neural circuitry that stimulates feeding in the rat. Administration of d-fenfluramine (FEN) has been shown to rapidly inhibit feeding in the rat. Because food deprivation increases the levels and release of NPY in the paraventricular nucleus (PVN) of the hypothalamus, the aim of this study was to investigate whether the rapid anorectic effects of FEN in food-deprived (FD) rats are associated with alterations in the hypothalamic NPYergic system.

Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats.

We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ)-induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN.

Diverse effects of tachykinins on luteinizing hormone release in male rats: mechanism of action.

The tachykinins are a group of structurally related peptides found in the rat hypothalamus and anterior pituitary. We have evaluated the effects of four tachykinins on LH release in male rats. In intact male rats, intracerebroventricular (icv) injection of neurokinin A (NKA), neuropeptide K (NPK), and neuropeptide-gamma (NP gamma) elicited dose-related, transient increases in plasma LH.

Hypothalamic neuropeptide Y gene expression in rats on scheduled feeding regimen.

Recent evidence suggests that neuropeptide Y (NPY) is an important signal in the neural circuitry that controls feeding behavior. Previously we observed that in rats entrained to 4 h daily scheduled feeding regimen (SFR), NPY content and release in the paraventricular nucleus (PVN) was elevated but decreased rapidly in association with food consumption. In the present study, we investigated the pattern of hypothalamic NPY gene expression in SFR rats before and after food consumption by measuring the content of preproNPY mRNA in the medial basal hypothalamus (MBH).

Neuropeptide Y release is elevated from the microdissected paraventricular nucleus of food-deprived rats: an in vitro study.

Intracerebroventricular injection of neuropeptide Y (NPY) stimulates a robust dose-related feeding response in the rat. Experimental evidence attests to the view that the release of NPY in the paraventricular nucleus (PVN), a site richly innervated by NPY immunopositive fibers, is responsible for stimulation of feeding behavior. However, there is little information on the neuroendocrine factors involved in regulation of NPY release, in part due to the unavailability of reliable techniques to monitor PVN NPY release.

Nephrotic-range proteinuria associated with right atrial myxoma.

A case of right atrial myxoma presenting with right heart failure and proteinuria is described. Proteinuria was variable and this corresponded with the degree of systemic venous congestion. On one occasion the proteinuria was within the nephrotic range.

Steroidal regulation of hypothalamic neuropeptide Y release and gene expression.

Neuropeptide Y (NPY) readily stimulates the release of hypothalamic LHRH and pituitary LH release in intact and gonadal steroid-primed gonadectomized rats. We have now tested the hypothesis that the release and synthesis of hypothalamic NPY may be regulated by gonadal steroids. To measure the effects of gonadal hormones on NPY release, a permanent push-pull cannula was implanted in the anterior pituitary (AP) of sham castrated (controls) or castrated (CAST) male rats, and 1 week later, the AP was perfused with artificial cerebrospinal fluid over a 3-4 h period.