Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

The discovery of the peptide hormone ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, yielded the surprising result that the principal site of ghrelin synthesis is the stomach and not the hypothalamus Although ghrelin is likely to regulate pituitary growth hormone (GH) secretion along with GH-releasing hormone and somatostatin, GHS receptors have also been identified on hypothalamic neurons and in the brainstem Apart from potential paracrine effects, ghrelin may thus offer an endocrine link between stomach, hypothalamus and pituitary, suggesting an involvement in regulation of energy balance Here we show that peripheral daily administration of ghrelin caused weight gain by reducing fat utilization in mice and rats Intracerebroventricular administration of ghrelin generated a dose-dependent increase in food intake and body weight Rat serum ghrelin concentrations were increased by fasting and were reduced by re-feeding or oral glucose administration, but not by water ingestion We propose that ghrelin, in addition to its role in regulating GH secretion, signals the hypothalamus when an increase in metabolic efficiency is necessary

Ghrelin induces adiposity in rodents.

Ghrelin is an acylated peptide that stimulates the release of growth hormone from the pituitary. Ghrelin-producing neurons are located in the hypothalamus, whereas ghrelin receptors are expressed in various regions of the brain, which is indicative of central-and as yet undefined-physiological functions. Here we show that ghrelin is involved in the hypothalamic regulation of energy homeostasis. Intracerebroventricular injections of ghrelin strongly stimulated feeding in rats and increased body weight gain. Ghrelin also increased feeding in rats that are genetically deficient in growth hormone. Anti-ghrelin immunoglobulin G robustly suppressed feeding. After intracerebroventricular ghrelin administration, Fos protein, a marker of neuronal activation, was found in regions of primary importance in the regulation of feeding, including neuropeptide Y6 (NPY) neurons and agouti-related protein (AGRP) neurons. Antibodies and antagonists of NPY and AGRP abolished ghrelin-induced feeding. Ghrelin augmented NPY gene expression and blocked leptin-induced feeding reduction, implying that there is a competitive interaction between ghrelin and leptin in feeding regulation. We conclude that ghrelin is a physiological mediator of feeding, and probably has a function in growth regulation by stimulating feeding and release of growth hormone.

A role for ghrelin in the central regulation of feeding.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

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Antibiotic resistance—the need for global solutions

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

https://www.physiology.org/doi/pdf/10.1152/physrev.00012.2004

Ghrelin: Structure and Function

Unique methods are disclosed to determine the relative infectivity of each of multiple species of Eimeria in a multivalent live vaccine. Genomic deoxyribonucleic acid (DNA) is extracted from intestinal epithelia and mucosa of vaccinated birds and amplified using the polymerase chain reaction (PCR). The reaction allows efficient amplification of fragments from every small subunit ribosomal RNA (ssrRNA) gene in the target pool. Unique species-specific hybridization probes complimentary to sequences within the heterogeneous pool of PCR products are used to quantitate the relative levels of each of the Eimeria species in the infected hosts. The same unique probes are used to identify and quantitate species specific ssrRNA sequences in total RNA extracted from intestinal epithelia and mucosa of vaccinated chickens. The same unique probes are also used to identify and quantitate species specific ssrRNA sequences in genomic DNA isolated from mixed oocyst population purified from fecal material obtained from vaccinated chickens.

Jennifer W. Anderson

Papers

Species-specific method for identifying infecticity of eimeria species.