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Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related(More)
The pituitary develops from the interaction of the infundibulum, a region of the ventral diencephalon, and Rathke's pouch, a derivative of oral ectoderm. Postnatally, its secretory functions are controlled by hypothalamic neurons, which also derive from the ventral diencephalon. In humans, mutations affecting the X-linked transcription factor SOX3 are(More)
Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that for GH-releasing hormone (GHRH). We have studied the hypothalamic expression and regulation of this receptor by in situ hybridization using a homologous riboprobe for rat GHS-R. GHS-R mRNA is prominently expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in(More)
GH-releasing hexapeptide (GHRP-6) is a synthetic secretagogue that stimulates the release of GH by acting at both hypothalamic and pituitary sites. GHRPs also consistently elicit small, but significant, increases in plasma concentrations of ACTH and adrenal steroids. As these secretagogues do not release ACTH directly, they probably interact with the(More)
Hypothalamic sensitivity to leptin has been suggested to be important for regulation of body fat mass. Mice heterozygous for a mutation in the leptin receptor (leptin-R) have an increased body fat mass suggesting that the abundance of leptin-R may be an important determinator of leptin sensitivity. Leptin-R cDNAs from several species contain alternative(More)
Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for(More)
Besides stimulating GH release, some GH secretagogues also release ACTH and adrenal steroids. Several novel classes of potent GH secretagogues have recently been described, and we have now tested their ability to release corticosterone in conscious normal rats. All analogs that released GH also stimulated corticosterone release to some degree, though the(More)
Using slices of rat hypothalamus maintained in vitro, we have examined release of oxytocin and vasopressin under conditions of increased neuronal activity. We report here that when the supraoptic or paraventricular nucleus is depolarized with high K+ solutions, hormone is released into areas close to the nucleus. Similar experiments with guinea pig(More)
The ultradian pulsatile pattern of growth hormone (GH) secretion is markedly sexually dimorphic in rodents as in primates, but the neuroanatomical mechanisms of this phenomenon are not clear. In the arcuate nucleus of the hypothalamus, GH-releasing hormone (GHRH) neurones receive somatostatinergic inputs through the sst2A receptor (sst2A-R) and the(More)
Recent evidence suggests that alterations in insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) can increase mammalian life span. For example, in several mouse mutants, impairment of the growth hormone (GH)/IGF1 axis increases life span and also insulin sensitivity. However, the intracellular signaling route to altered mammalian aging remains(More)