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A J van der Lely
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W W de Herder
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J A M J L Janssen
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S W J Lamberts
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We have studied the physiological and clinical relevance of measurements of serum total and free IGF-I and IGF-binding protein-3 (IGFBP-3) in 57 previously untreated patients with active acromegaly (32 males, 25 females; mean age 47 years) as compared with sex- and age-matched normal healthy controls. Serum total and free IGF-I, but not IGFBP-3, are suitable biochemical parameters for screening for acromegaly. In acromegalics, the mean 24 h serum GH, total IGF-I and IGFBP-3 levels tend to decrease with age. However, in our series of patients, mean 24 h serum GH levels, IGFBP-3, total and free IGF-I do not correlate with disease activity in acromegaly.

Journal of Endocrinology (1997) 155, S9–S13

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P J D Delhanty Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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B C J van der Eerden Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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M van der Velde Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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C Gauna Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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H A P Pols Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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H Jahr Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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H Chiba Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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A J van der Lely Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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J P T M van Leeuwen Departments of Internal Medicine and
Orthopedics, Erasmus Medical Centre, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands
Department of Pathology, Sapporo Medical University School of Medicine, University of Sapporo, S-1, W-17, Sapporo 060-8556, Japan

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Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin’s cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin. Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.

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