Melanocyte-Stimulating Hormone Stimulates Oxytocin Release from the Dendrites of Hypothalamic Neurons While Inhibiting Oxytocin Release from Their Terminals in the Neurohypophysis (original) (raw)
Related papers
The Journal of Neuroscience, 2003
The peptides ␣-melanocyte stimulating hormone (␣-MSH) and oxytocin, when administered centrally, produce similar behavioral effects. ␣-MSH induces Fos expression in supraoptic oxytocin neurons, and ␣-MSH melanocortin-4 receptors (MC4Rs) are highly expressed in the supraoptic nucleus, suggesting that ␣-MSH and oxytocin actions are not independent. Here we investigated the effects of ␣-MSH on the activity of supraoptic neurons. We confirmed that ␣-MSH induces Fos expression in the supraoptic nucleus when injected centrally and demonstrated that ␣-MSH also stimulates Fos expression in the nucleus when applied locally by retrodialysis. Thus ␣-MSH-induced Fos expression is not associated with electrophysiological excitation of supraoptic neurons because central injection of ␣-MSH or selective MC4 receptor agonists inhibited the electrical activity of oxytocin neurons in the supraoptic nucleus recorded in vivo. Consistent with these observations, oxytocin secretion into the bloodstream decreased after central injection of ␣-MSH. However, MC4R ligands induced substantial release of oxytocin from dendrites in isolated supraoptic nuclei. Because dendritic oxytocin release can be triggered by changes in [Ca 2ϩ ] i , we measured [Ca 2ϩ ] i responses in isolated supraoptic neurons and found that MC4R ligands induce a transient [Ca 2ϩ ] i increase in oxytocin neurons. This response was still observed in low extracellular Ca 2ϩ concentration and probably reflects mobilization of [Ca 2ϩ ] i from intracellular stores rather than entry via voltage-gated channels. Taken together, these results show for the first time that a peptide, here ␣-MSH, can induce differential regulation of dendritic release and systemic secretion of oxytocin, accompanied by dissociation of Fos expression and electrical activity.
PubMed, 2003
The peptides alpha-melanocyte stimulating hormone (alpha-MSH) and oxytocin, when administered centrally, produce similar behavioral effects. alpha-MSH induces Fos expression in supraoptic oxytocin neurons, and alpha-MSH melanocortin-4 receptors (MC4Rs) are highly expressed in the supraoptic nucleus, suggesting that alpha-MSH and oxytocin actions are not independent. Here we investigated the effects of alpha-MSH on the activity of supraoptic neurons. We confirmed that alpha-MSH induces Fos expression in the supraoptic nucleus when injected centrally and demonstrated that alpha-MSH also stimulates Fos expression in the nucleus when applied locally by retrodialysis. Thus alpha-MSH-induced Fos expression is not associated with electrophysiological excitation of supraoptic neurons because central injection of alpha-MSH or selective MC4 receptor agonists inhibited the electrical activity of oxytocin neurons in the supraoptic nucleus recorded in vivo. Consistent with these observations, oxytocin secretion into the bloodstream decreased after central injection of alpha-MSH. However, MC4R ligands induced substantial release of oxytocin from dendrites in isolated supraoptic nuclei. Because dendritic oxytocin release can be triggered by changes in [Ca2+]i, we measured [Ca2+]i responses in isolated supraoptic neurons and found that MC4R ligands induce a transient [Ca2+]i increase in oxytocin neurons. This response was still observed in low extracellular Ca2+ concentration and probably reflects mobilization of [Ca2+]i from intracellular stores rather than entry via voltage-gated channels. Taken together, these results show for the first time that a peptide, here alpha-MSH, can induce differential regulation of dendritic release and systemic secretion of oxytocin, accompanied by dissociation of Fos expression and electrical activity.
Neurohypophysial Peptides and the Regulation of Melanophore Stimulating Hormone (MSH) Secretion
Integrative and Comparative Biology, 1977
SYNOPSIS. Melanophore stimulating hormone (MSH) secretion from the vertebrate pars intermedia is regulated as for other pituitary hormones, by the hypothalamus. Removal of the pituitary from hypothalamic control results in an autonomous uninhibited secretion of MSH. Thus, as for prolactin, the hypothalamus exerts a tonic inhibitory control over MSH secretion. The nature of this inhibitory mechanism is presently being debated with two general models being considered. It is suggested by some investigators that peptides of neurohypophysial hormone origin act as MSH releasing and inhibiting factors (MRF's and MIF's, respectively). In this scheme, the neurohypophysial hormones such as oxytocin would serve as prohormones which by enzymatic cleavage by hypothalamic enzymes would yield MSH releasing and/or inhibiting factors. It is suggested that the terminal tripeptide side chain is an MIF whereas the N-terminal pentapeptide sequence of oxytocin is an MRF. The data supporting this hypothesis comes from work of a few investigators that espouse this scheme. To our knowledge, the so-called MSH releasing and inhibiting factors have proven ineffective in the hands of all other investigators in regulating MSH release. A large number of investigators support the view that MSH secretion is regulated by neurotransmitters. As for the prolactin inhibiting factor (PIF), MIF may be a catecholamine (dopamine). Other neurotransmitters such as serotonin and/or acetylcholine may serve as an MRF. Many investigators have demonstrated the direct affect of these neurotransmitters on MSH secretion. The possible role of neurohypophysial hormones in the control of other pituitary hormone secretions is discussed. The possible relationships between neurohypophysial peptides, MSH, and the pineal are reviewed. More data needs to be provided before we add to the list of physiological functions of neurohypophysial hormones the role of these peptides as hypothalamic pituitary inhibiting and/or releasing factors.
Hypothalamic α-melanocyte-stimulating hormone (α-MSH) is not under dopaminergic control
Brain Research, 1987
A possible dopaminergic regulation of hypothalamic proopiomelanocortin (POMC)-containing neurons has been investigated in rats by means of in vivo and in vitro approaches. Acute or 3-weeks chronic in vivo treatments with the dopaminergic agonists apomorphine (1 mg/kg; s.c.) and 2-Bra -ergocriptine (2.5 mg/kg; s.c.) or the dopaminergic antagonist haloperidol (0.15-3 mg/kg; i.p.) had no significant effect on the concentration of a-melanocyte-stimulating hormone (a-MSH) in two hypothalamic regions: arcuate nucleus (AN) and dorsolateral area (DLH). In the same way, chronic administration of the dopaminergic agonists or antagonist did not induce any change in hypothalamic contents of fl-endorphin, another peptide derived from POMC. Reverse-phase high-performance liquid chromatographic analysis revealed that acetic acid extracts of AN and DLH both contained two major forms of a-MSH-like peptides: deacetylated a-MSH and authentic a-MSH. The ratio between these two forms was not altered after acute haloperidoi treatment (3 rng/kg, i.p.). The possible effect of dopamine on th e release of hypothalamic a-MSH was studied in vitro using perifused rat hypothalamic slices. Infusion of dopamine (10-7-10-5M) or its antagonist haloperidol (10-SM) had no effect on spontaneous a-MSH release from hypothalamic tissue. In addition, none of these drugs had any effect on potassium (50 mM)-induced a-MSH release. It is concluded that dopaminergic neurons are not involved in the regulation of synthesis, post-translational processing (acetylation) or release of hypothalamic a-MSH.
2003
Both central ␣-melanocyte-stimulating hormone and corticotropin-releasing hormone (CRH) have been implicated in feeding and neuroendocrine mechanisms. The anatomical overlap and functional similarities between these two neurotransmitter systems led to the hypothesis that CRH might act as one of the mediators of the central actions of the melanocortin system. By double-labeling in situ hybridization, a subpopulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN) were shown to contain the melanocortin-4 receptor (MC4R), concentrated in the ventromedial part of the parvicellular PVN (up to 33%). Intracerebroventricular injection of melanocortin agonist MTII to conscious and freely moving rats induced a rapid induction of CRH gene transcription in the PVN. This effect was accompanied by a rise in plasma corticosterone levels in a dose-and time-dependent manner, with the maximum response observed 30 min after MTII injection. MTII (0.5 nmol)-induced increase in plasma corticosterone was attenuated by the selective MC4R antagonist HS014 (0.25-1.0 nmol) and nonselective CRH receptor antagonist ␣-helical-CRH 9-41 (0.125-0.5 nmol) in a dose-dependent manner. Moreover, the anorectic effect of MTII was evaluated at 1, 2, and 24 hr after intracerebroventricular injection. Approximately half of the inhibitory effect of MTII (0.5 nmol) on food intake was reversed by pretreatment with ␣-helical-CRH 9-41 at 0.25 and 0.5 nmol doses. Collectively, these results provide evidence that CRH acts as a downstream mediator of melanocortin signaling and contributes to the mechanisms by which the central melanocortin system controls feeding and neuroendocrine responses.
The Journal of Neuroscience
Both central ␣-melanocyte-stimulating hormone and corticotropin-releasing hormone (CRH) have been implicated in feeding and neuroendocrine mechanisms. The anatomical overlap and functional similarities between these two neurotransmitter systems led to the hypothesis that CRH might act as one of the mediators of the central actions of the melanocortin system. By double-labeling in situ hybridization, a subpopulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN) were shown to contain the melanocortin-4 receptor (MC4R), concentrated in the ventromedial part of the parvicellular PVN (up to 33%). Intracerebroventricular injection of melanocortin agonist MTII to conscious and freely moving rats induced a rapid induction of CRH gene transcription in the PVN. This effect was accompanied by a rise in plasma corticosterone levels in a dose-and time-dependent manner, with the maximum response observed 30 min after MTII injection. MTII (0.5 nmol)-induced increase in plasma corticosterone was attenuated by the selective MC4R antagonist HS014 (0.25-1.0 nmol) and nonselective CRH receptor antagonist ␣-helical-CRH 9-41 (0.125-0.5 nmol) in a dose-dependent manner. Moreover, the anorectic effect of MTII was evaluated at 1, 2, and 24 hr after intracerebroventricular injection. Approximately half of the inhibitory effect of MTII (0.5 nmol) on food intake was reversed by pretreatment with ␣-helical-CRH 9-41 at 0.25 and 0.5 nmol doses. Collectively, these results provide evidence that CRH acts as a downstream mediator of melanocortin signaling and contributes to the mechanisms by which the central melanocortin system controls feeding and neuroendocrine responses.
α-Melanocyte-stimulating hormone (α-MSH) release from perifused rat hypothalamic slices
Brain Research, 1987
A perifusion system was developed to investigate the control of a-melanocyte-stimulating hormone (a-MSH) release from rat brain. Hypothalamic slices were perifused with Krebs-Ringer bicarbonate (KRB) medium supplemented with glucose, bacitracin and bovine serum albumine. Fractions were set apart every 3 min and a-MSH levels were measured by means of a specific and sensitive radioimmunoassay method. Hypothalamic tissue in normal KRB medium released a-MSH at a constant rate corresponding to 0.1% of the total hypothalamic content per 3 min. The basal release was not altered by Ca 2+ omission in the medium or addition of the sodium channel blocker tetrodotoxine (TTX). Depolarizing agents such as potassium (50 mM) and veratridine (50/~M), which is known to increase Na + conductance, significantly stimulated a-MSH release in a Ca2+-dependent manner. When Na+-channels were blocked by TTX (0.5/~M) the stimulatory effect of veratridine was completely abolished whereas the K+-evoked release was unaffected. These findings suggest that: (1) voltage-dependent sodium channels are present on a-MSH hypothalamic neurons; (2) depolarization by K + induces a marked stimulation of a-MSH release; (3) K +-and veratridine-evoked releases are calcium-dependent. Altogether, these data provide evidence for a neurotransmitter or neuromodulator role for a-MSH in rat hypothalamus.