Temporal patterns of increased growth hormone secretion in mice after oral administration of L-ornithine: possible involvement of ghrelin receptors.

l-Ornithine is known to stimulate growth hormone (GH) release in mammals. Here, we demonstrated that increases in plasma GH levels after oral administration of l-ornithine were first observed 150 min after administration, and the elevated levels were sustained for more than 90 min in mice. The increase was significantly delayed compared with the reported timing of plasma and tissue levels of l-ornithine after administration. The l-ornithine-induced increase in GH release was completely blocked by [D-Lys3]-GHRP-6, a ghrelin receptor antagonist, but not by cyclosomatostatin or JV-1-38, antagonists of somatostatin and GH-releasing hormone, respectively. These results suggest the involvement of ghrelin receptor-mediated pathways in l-ornithine-induced increases in GH release.

Photoperiodic changes in hippocampal neurogenesis and plasma metabolomic profiles in relation to depression-like behavior in mice.

Photoperiod alters affective behaviors and brain neuroplasticity in several mammalian species. We addressed whether neurogenesis and signaling pathways of insulin-like growth factor-I (IGF-I), a key modulator of neuroplasticity, are regulated by photoperiod in C57BL/6 J mice, a putative model of seasonal affective disorder. We also examined the effects of photoperiod on plasma metabolomic profiles in relation to depression-like behavior to understand a possible linkage between peripheral metabolism and behavior. Mice that were maintained under long-day conditions (LD) exhibited a higher number of 5-bromo-2'-deoxyuridine-positive cells and higher levels of astrocyte marker in the dentate gyrus of the hippocampus compared to that of mice under short-day conditions (SD). Plasma IGF-I levels and levels/expression of IGF-I signaling molecules in the hippocampus (Brn-4, NeuroD1, and phospho-Akt) involved in neuronal proliferation and differentiation were higher in the mice under LD. Metabolome analysis using plasma of the mice under LD and SD identified several metabolites that were highly correlated with immobility in the forced swim test, a depression-like behavior. Negative correlations with behavior occurred in the levels of 23 metabolites, including metabolites related to neurogenesis and antidepressant-like effects of exercise, metabolites in the biosynthesis of arginine, and the occurrence of branched chain amino acids. Three metabolites had positive correlations with the behavior, including guanidinosuccinic acid, a neurotoxin. Taken together, photoperiodic responses of neurogenesis and neuro-glial organization in the hippocampus may be involved in photoperiodic alteration of depression-like behavior, mediated through multiple pathways, including IGF-I and peripheral metabolites.

Procedure for increasing the detection responses of estrogens in LC-MS based on introduction of a nitrobenzene moiety followed by electron capture atmospheric pressure chemical ionization.

A practical procedure for determining estrogens in biological fluids has been studied using liquid chromatography-electron capture atmospheric pressure chemical ionization-mass spectrometry combined with derivatization. Among the commercially available reagents (4-nitrobenzoyl chloride, 2,4-dinitrofluorobenzene, 4-nitrobenzenesulfonyl chloride and 4-nitrobenzyl bromide), 4-nitrobenzenesulfonyl chloride was of the most practical use; it rapidly and quantitatively reacted with estrogens and increased the detection responses by 8-23 times. The derivatization method allowed the reproducible and accurate quantification of serum and urine estrone and estradiol of a pregnant woman, which is useful for diagnosis of the fetoplacental function, with small amounts (10 mul) of sample and a simple pretreatment procedure. Tatsuya Higashiis Associate Professor of the Laboratory of Clinical Analytical Sciences (Professor Kazutake Shimada's research group) at the Graduate School of Natural Science and Technology of Kanazawa University. He received the Japan Society for Analytical Chemistry Award for Young Scientists in 2003 and the Pharmaceutical Society of Japan Award for Young Scientists in 2006. His current research interests are the development of methods for increasing sensitivity in LC-MS to detect and characterize trace amounts of biologically active steroids, such as estrogens, androgens and neuroactive steroids.