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  • 1
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100–1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the hypothalamic-pituitary-gonadal axis. These effects are likely to be mediated via the hypothalamic LHRH system.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Melanin-concentrating hormone (MCH) is implicated in the control of a number of hormonal axes including the hypothalamic-pituitary adrenal (HPA) axis. Previous studies have shown that there is evidence for both a stimulatory and an inhibitory action on the HPA axis; therefore, we attempted to further characterize the effects of MCH on this axis. Intracerebroventricular injection of MCH increased circulating adrenocorticotropic hormone (ACTH) at 10 min post injection. Injection of MCH directly into the paraventricular nucleus (PVN) was found to increase both circulating ACTH and corticosterone 10 min after injection. Additionally, MCH was found to increase corticotropin-releasing factor (CRF) release from hypothalamic explants, and this effect was abolished by the specific SLC-1 antagonist SB-568849. Neuropeptide EI, a peptide from the same precursor as MCH was also found to increase CRF release from explants. These results suggest that MCH has a stimulatory role in the HPA axis via SLC-1, and that MCH exerts its effects predominantly through the PVN CRF neuronal populations
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A number of neuropeptides implicated in the hypothalamic regulation of appetite are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic. The pro-opiomelanocortin (POMC) product alpha-melanocyte-stimulating hormone (α-MSH) is anorectic. Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) decreases food intake. However, recent results show that CART is orexigenic when injected into discrete hypothalamic nuclei. There is almost complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of CART-containing neurones in the Arc also contain POMC mRNA. We investigated possible interactions between these neuropeptides in vitro using a rat hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to hypothalamic explants significantly increased release of Agrp(83-132)-immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of CART(55-102)-IR and α-MSH-IR from hypothalamic explants. Agrp(83-132) (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. Agrp(83-132) (10 and 100 nm) significantly decreased the release of CART(55-102)-IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55-102) to hypothalamic explants resulted in a significant increase in NPY-IR release. Administration of 10 nm CART(55-102) to hypothalamic explants significantly increased the release of Agrp(83-132)-IR. NDP-MSH (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. NDP-MSH (10 and 100 nm) significantly increased the release of Agrp(83-132)-IR from hypothalamic explants. These data suggest that orexigenic neuropeptides in the arcuate nucleus stimulate the release of each other, perhaps reinforcing orexigenic behaviour via a positive-feedback loop. Our results are also in keeping with the possibility that the melanocortin-3 receptor in the arcuate nucleus may influence the release of arcuate neuropeptides.
    Type of Medium: Electronic Resource
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