Effects of high-tryptophan diet on pre- and postnatal development in rats: a morphological study
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Tryptophan is an essential amino acid, precursor of serotonin. Serotonin (5HT) regulates the secretion of pituitary growth hormone (GH), which in turn stimulates the liver to produce insulin-like growth factor-I (IGF-I) that is necessary for development and growth. The aim of our study was to investigate the effects of an excess of tryptophan in the diet of pregnant rats on the differentiation of skeletal muscle tissue.
We conducted an immunohistochemical study on the IGF-I expression in hepatic and muscle tissues in offspring, and then, we associated this molecular data with morphological effects on the structure of the muscle fibers and hepatic tissue at different postnatal weeks, from birth to sexual maturity. Measurements of 5HT, GH in blood, and of tryptophan hydroxylase (Tph) activity in gastrointestinal tracts tissue were also taken.
Hyperserotonemia and higher values of Tph activity were detected in both pregnant rats and pups. Very low levels of GH were detected in experimental pups. Morphological alterations of the muscle fibers and lower IGF-I expression in hepatic and muscle tissue in pups were found.
Our data suggest that an excess of tryptophan in the diet causes hyperserotonemia in fetus. Hyperserotonemia results in an excess of serotonin in the brain where it has an adverse effect on the development of serotonergic neurons. The affected neurons do not regulate optimally the secretion of pituitary GH that consequently decreases. This limits stimulation in the liver to produce IGF-I, crucial for development and growth of pups.
KeywordsTryptophan Serotonin Growth hormone Insulin-like growth factor Development Diet
The study was funded by the Department of Bio-Medical Sciences, University of Catania. The authors would like to thank Prof. Iain Halliday for commenting and making corrections to the paper and Mr. Pietro Asero for technical support in the laboratory.
Conflict of interest
The authors declare that they have no conflict of interest.
Experiment was performed in accordance with the European Communities Council Directive (86/609/EEC) and Italian Animal Protection Law (116/1992).
- 3.Young S (1986) The clinical psychopharmacology of tryptophan. In: Wurtman RJ, Wurtman JJ (eds), New YorkGoogle Scholar
- 12.Hall TR, Harvey S, Chadwick A (1984) Serotonin and acetylcholine affect the release of prolactin and growth hormone from pituitary glands of domestic fowl in vitro in the presence of hypothalamic tissue. Acta Endocrinol (Copenh) 105:455–462Google Scholar
- 16.López F, Gónzalez D, Aguilar E (1986) Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries. Acta Endocrinol (Copenh) 113:317–322Google Scholar
- 18.Camarero G, Avendano C, Fernandez-Moreno C, Villar A, Contreras J, de Pablo F, Pichel JG, Varela-Nieto I (2001) Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice. J Neurosci 21:7630–7641Google Scholar
- 26.Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75:59–72Google Scholar
- 31.Lowry OH, Rosebrough NJ, Farr AL, Randal RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- 36.Pichler K, Loreto C, Leonardi R, Reuber T, Weinberg AM, Musumeci G (2013) In rat with glucocorticoid-induced osteoporosis, RANKL is downregulated in bone cells by physical activity (treadmill and vibration stimulation training). Histol Histopathol (in press)Google Scholar
- 37.Musumeci G, Loreto C, Leonardi R, Castorina S, Giunta S, Carnazza ML, Trovato FM, Pichler K, Weinberg AM (2013) The effects of physical activity on apoptosis and lubricin expression in articular cartilage in rats with glucocorticoid-induced osteoporosis. Bone and Mineral Research (in press)Google Scholar
- 39.Blazevic S, Dolenec P, Hranilovic D (2011) Physiological consequences of perinatal treatment of rats with 5-hydroxytryptophan. Periodicum Biologorum 113:81–86Google Scholar
- 40.Duan C (1998) Nutritional and developmental regulation of insulin-like growth factors in fish. J Nutr 128:306S–314SGoogle Scholar
- 43.Davies K, Richardson G, Akmentin W, Acuff V, Fenstermacher J (1996) The microarchitecture of cerebral vessels. In: Courad P, Scherman D (eds) The cerebral vascular symposium, biology and physiology of the blood-brain barrier. Plenum Press, New YorkGoogle Scholar
- 44.Philippou A, Maridaki M, Halapas A, Koutsilieris M (2007) The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. In Vivo 21:45–54Google Scholar
- 45.Scicchitano BM, Rizzuto E, Musarò A (2009) Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY) 1:451–457Google Scholar