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Abstract
The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 μg FSH/l (high FSH) but not 20 μg FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture.
DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I. A similar increase in DNA synthesis was observed after 48 h when granulosa cells were treated with low FSH alone, which did not induce LH receptor expression. These results indicate that 1) growth and differentiation of granulosa cells are regulated inversely; 2) FSH and IGF-I act together to induce LH receptor expression; and 3) action of IGF-I is dependent on the presence of FSH.
Journal of Endocrinology (1994) 141, 301–308
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Abstract
The effect of human GH (hGH) on the regulation of epidermal growth factor (EGF) receptor was investigated during differentiation of FSH-treated rat granulosa cells, which has been reported to be mediated by a cAMP-dependent mechanism. By measuring the binding of [125I]iodo-EGF to the intact cells, FSH was shown to cause increases in the number of EGF binding sites after culture for 72 h. When granulosa cells were cultured with hGH, the number of FSH-induced EGF binding sites was augmented, with a half-maximal effect at about 10 μg hGH/l and a maximal stimulatory concentration of 100 μg/l. The stimulatory effect of hGH was absolutely dependent on insulin which by itself showed stimulatory effects on EGF binding sites. Scatchard analysis of EGF binding sites indicated that treatment with hGH increased the number of EGF binding sites (17 200 sites/cell after treatment with FSH; 31 700 sites/cell after FSH plus hGH), but did not alter the binding affinity. The augmentation was observed after culturing for 48 h and increased progressively with time, reaching 280% of the level after FSH treatment by 120 h. Although progesterone synthesis was increased by hGH, the markers of cell differentiation such as cAMP synthesis and LH binding sites were suppressed, indicating hGH inhibition of the cAMP-mediated signal. The action of hGH on the EGF binding sites was not accompanied by cell proliferation. These findings indicate that hGH has a novel action on the regulation of rat granulosa cell EGF binding sites and that the granulosa cell may possess both cAMP-dependent and -independent mechanisms for expression of EGF binding sites.
Journal of Endocrinology (1994) 142, 69–75
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Ghrelin, a 28 amino acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. The fact that administration of ghrelin, centrally or peripherally, stimulates both food intake and GH secretion suggests that stomach ghrelin has an important role in the growth of rats. We used immunohistochemistry and radioimmunoassay to determine the age at which ghrelin-immunostained cells begin to appear in the rat stomach. Ghrelin-immunoreactive cells were found to be expressed in the fetal stomach from pregnancy day 18. The number of ghrelin-immunoreactive cells in the fetal stomach increased as the stomach grew. The amount of ghrelin in the glandular part of the rat stomach also increased, in an age-dependent manner, from the neonatal stage to adult. Eight hours of milk restriction significantly decreased the ghrelin concentration in the stomachs of 1-week-old rats, and increased the ghrelin concentration in their plasma. Administration of ghrelin to 1- and 3-week-old rats increased plasma GH concentrations. The daily subcutaneous administration of ghrelin to pregnant rats from day 15 to day 21 of pregnancy caused an increase in body weight of newborn rats. In addition, daily subcutaneous administration of ghrelin to neonatal rats from birth advanced the day of vaginal opening from day 30.7+/-0.94 to day 27.9+/-0.05. These results suggest that ghrelin may be involved in neonatal development.
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ABSTRACT
The cytoplasmic concentration of free calcium was measured using aequorin, a calcium-sensitive photoprotein. The Ca2+ ionophore A23187 induced a rise in cytoplasmic free calcium and iodide discharge in cultured porcine thyroid cells. The minimum dose of A23187 effecting an increase in cytoplasmic free calcium induced iodide discharge. The A23187-induced rise in cytoplasmic free calcium was followed by iodide discharge. The results indicate that A23187-induced iodide discharge is mediated by a rise in the cytoplasmic concentration of free calcium.
J. Endocr. (1987) 115, 477–480
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We purified ghrelin from stomach extracts of a teleost fish, the Japanese eel (Anguilla japonica) and found that it contained an amide structure at the C-terminal end. Two molecular forms of ghrelin with 21 amino acids were identified by cDNA and mass spectrometric analyses: eel ghrelin-21, GSS(O-n-octanoyl)FLSPSQRPQGKDKKPP RV-amide and eel ghrelin-21-C10, GSS(O-n-decanoyl) FLSPSQRPQGKDKKPPRV-amide. Northern blot and RT-PCR analyses revealed high gene expression in the stomach. Low levels of expression were found only in the brain, intestines, kidney and head kidney by RT-PCR analysis. Eel ghrelin-21 increased plasma growth hormone (GH) concentrations in rats after intravenous injection; the potency was similar to that of rat ghrelin. We also examined the effect of eel ghrelin on the secretion of GH and prolactin (PRL) from organ-cultured tilapia pituitary. Eel ghrelin-21 at a dose of 0.1 nM stimulated the release of GH and PRL, indicating that ghrelin acts directly on the pituitary. The present study revealed that ghrelin is present in fish stomach and has the ability to stimulate the secretion of GH from fish pituitary. A novel regulatory pathway of GH secretion by gastric ghrelin seems to be conserved from fish to human.
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Ghrelin, a 28-amino-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys(12)]-ghrelin[1-11]) region and one raised against the C-terminal ([Cys(0)]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n- octanoylated Ser 3 (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the anti-ghrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.
Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima 739-8528, Japan
National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 ± 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 μg/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44± 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P < 0.01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P < 0.05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.
Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Post-genome Project, Department of Experimental Therapeutics, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Department of Clinical Innovative Medicine, and
Department of Clinical Trial Design and Management, Kyoto University Hospital, Kyoto 606-8507, Japan
Translational Research Center, Kyoto University Hospital, and Department of Geriatric Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan
Center for Southeast Asian Studies, Kyoto University, Kyoto 606-8501, Japan
Kyoto Preventive Medical Centre, Kyoto 604-8491, Japan
Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were ≥ 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 ± 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.
