Skip to main content
Top
Published in: European Journal of Nutrition 1/2014

01-02-2014 | Original Contribution

Effects of high-tryptophan diet on pre- and postnatal development in rats: a morphological study

Authors: Paola Castrogiovanni, Giuseppe Musumeci, Francesca Maria Trovato, Rosanna Avola, Gaetano Magro, Rosa Imbesi

Published in: European Journal of Nutrition | Issue 1/2014

Login to get access

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
Literature
1.
go back to reference Mateos SS, Sánchez CL, Paredes SD, Barriga C, Rodríguez AB (2009) Circadian levels of serotonin in plasma and brain after oral administration of tryptophan in rats. Basic Clin Pharmacol Toxicol 104:52–59CrossRef Mateos SS, Sánchez CL, Paredes SD, Barriga C, Rodríguez AB (2009) Circadian levels of serotonin in plasma and brain after oral administration of tryptophan in rats. Basic Clin Pharmacol Toxicol 104:52–59CrossRef
2.
go back to reference Choi S, DiSilvio B, Fernstrom MH, Fernstrom JD (2011) The chronic ingestion of diets containing different proteins produces marked variations in brain tryptophan levels and serotonin synthesis in the rat. Neurochem Res 36:559–565CrossRef Choi S, DiSilvio B, Fernstrom MH, Fernstrom JD (2011) The chronic ingestion of diets containing different proteins produces marked variations in brain tryptophan levels and serotonin synthesis in the rat. Neurochem Res 36:559–565CrossRef
3.
go back to reference Young S (1986) The clinical psychopharmacology of tryptophan. In: Wurtman RJ, Wurtman JJ (eds), New York Young S (1986) The clinical psychopharmacology of tryptophan. In: Wurtman RJ, Wurtman JJ (eds), New York
4.
go back to reference Racke K, Reimann A, Schwörer H, Kilbinger H (1995) Regulation of 5-HT release from enterochromaffin cells. Behav Brain Res 73:83–87CrossRef Racke K, Reimann A, Schwörer H, Kilbinger H (1995) Regulation of 5-HT release from enterochromaffin cells. Behav Brain Res 73:83–87CrossRef
5.
go back to reference Whitaker-Azmitia PM (2001) Serotonin and brain development: role in human developmental diseases. Brain Res Bull 56:479–485CrossRef Whitaker-Azmitia PM (2001) Serotonin and brain development: role in human developmental diseases. Brain Res Bull 56:479–485CrossRef
6.
go back to reference Catalano M (2001) Functionally gene-linked polymorphic regions and genetically controlled neurotransmitters metabolism. Eur Neuropsychopharmacol 11:431–439CrossRef Catalano M (2001) Functionally gene-linked polymorphic regions and genetically controlled neurotransmitters metabolism. Eur Neuropsychopharmacol 11:431–439CrossRef
7.
go back to reference Lesch KP (2001) Variation of serotonergic gene expression: neurodevelopment and the complexity of response to psychopharmacologic drugs. Eur Neuropsychopharmacol 11:457–474CrossRef Lesch KP (2001) Variation of serotonergic gene expression: neurodevelopment and the complexity of response to psychopharmacologic drugs. Eur Neuropsychopharmacol 11:457–474CrossRef
8.
go back to reference Arnold MA, Fernstrom JD (1978) Serotonin receptor antagonists block a natural, short term surge in serum growth hormone levels. Endocrinology 103:1159–1163CrossRef Arnold MA, Fernstrom JD (1978) Serotonin receptor antagonists block a natural, short term surge in serum growth hormone levels. Endocrinology 103:1159–1163CrossRef
9.
go back to reference Collu R, Du Rusisseau P, Taché Y (1979) Role of putative neurotransmitters in prolactin, GH and LH response to acute immobilization stress in male rats. Neuroendocrinology 28:178–186CrossRef Collu R, Du Rusisseau P, Taché Y (1979) Role of putative neurotransmitters in prolactin, GH and LH response to acute immobilization stress in male rats. Neuroendocrinology 28:178–186CrossRef
10.
go back to reference Rabii J, Buonomo F, Scanes CG (1981) Role of serotonin in the regulation of growth hormone and prolactin secretion in the domestic fowl. J Endocrinol 90:355–358CrossRef Rabii J, Buonomo F, Scanes CG (1981) Role of serotonin in the regulation of growth hormone and prolactin secretion in the domestic fowl. J Endocrinol 90:355–358CrossRef
11.
go back to reference Casanueva FF, Villanueva L, Peñalva A, Cabezas-Cerrato J (1984) Depending on the stimulus, central serotoninergic activation by fenfluramine blocks or does not alter growth hormone secretion in man. Neuroendocrinology 38:302–308CrossRef Casanueva FF, Villanueva L, Peñalva A, Cabezas-Cerrato J (1984) Depending on the stimulus, central serotoninergic activation by fenfluramine blocks or does not alter growth hormone secretion in man. Neuroendocrinology 38:302–308CrossRef
12.
go back to reference 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) 105:455–462 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) 105:455–462
13.
go back to reference Westlund KN, Childs GV (1982) Localization of serotonin fibers in the rat adenohypophysis. Endocrinology 111:1761–1763CrossRef Westlund KN, Childs GV (1982) Localization of serotonin fibers in the rat adenohypophysis. Endocrinology 111:1761–1763CrossRef
14.
go back to reference Léránth C, Palkovits M, Krieger DT (1983) Serotonin immunoreactive nerve fibers and terminals in the rat pituitary–light- and electron-microscopic studies. Neuroscience 9:289–296CrossRef Léránth C, Palkovits M, Krieger DT (1983) Serotonin immunoreactive nerve fibers and terminals in the rat pituitary–light- and electron-microscopic studies. Neuroscience 9:289–296CrossRef
15.
go back to reference Payette RF, Gershon MD, Nunez EA (1985) Serotonergic elements of the mammalian pituitary. Endocrinology 116:1933–1942CrossRef Payette RF, Gershon MD, Nunez EA (1985) Serotonergic elements of the mammalian pituitary. Endocrinology 116:1933–1942CrossRef
16.
go back to reference 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) 113:317–322 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) 113:317–322
17.
go back to reference Saland LC (2001) The mammalian pituitary intermediate lobe: an update on innervation and regulation. Brain Res Bull 54:587–593CrossRef Saland LC (2001) The mammalian pituitary intermediate lobe: an update on innervation and regulation. Brain Res Bull 54:587–593CrossRef
18.
go back to reference 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 21:7630–7641 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 21:7630–7641
19.
go back to reference Duan C, Ren H, Gao S (2010) Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins: roles in skeletal muscle growth and differentiation. Gen Comp Endocrinol 167:344–351CrossRef Duan C, Ren H, Gao S (2010) Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins: roles in skeletal muscle growth and differentiation. Gen Comp Endocrinol 167:344–351CrossRef
20.
go back to reference Holt RI (2002) Fetal programming of the growth hormone-insulin-like growth factor axis. Trends Endocrinol Metab 13:392–397CrossRef Holt RI (2002) Fetal programming of the growth hormone-insulin-like growth factor axis. Trends Endocrinol Metab 13:392–397CrossRef
21.
go back to reference Powell-Braxton L, Hollingshead P, Warburton C, Dowd M, Pitts-Meek S, Dalton D, Gillett N, Stewart TA (1993) IGF-I is required for normal embryonic growth in mice. Genes Dev 7:2609–2617CrossRef Powell-Braxton L, Hollingshead P, Warburton C, Dowd M, Pitts-Meek S, Dalton D, Gillett N, Stewart TA (1993) IGF-I is required for normal embryonic growth in mice. Genes Dev 7:2609–2617CrossRef
22.
go back to reference Le Roith D, Scavo L, Butler A (2001) What is the role of circulating IGF-I? Trends Endocrinol Metab 12:48–52CrossRef Le Roith D, Scavo L, Butler A (2001) What is the role of circulating IGF-I? Trends Endocrinol Metab 12:48–52CrossRef
23.
go back to reference Cassano M, Quattrocelli M, Crippa S, Perini I, Ronzoni F, Sampaolesi M (2009) Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass. J Muscle Res Cell Motil 30:243–253CrossRef Cassano M, Quattrocelli M, Crippa S, Perini I, Ronzoni F, Sampaolesi M (2009) Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass. J Muscle Res Cell Motil 30:243–253CrossRef
24.
go back to reference D’Ercole AJ, Ye P, O’Kusky JR (2002) Mutant mouse models of insulin-like growth factor actions in the central nervous system. Neuropeptides 36:209–220CrossRef D’Ercole AJ, Ye P, O’Kusky JR (2002) Mutant mouse models of insulin-like growth factor actions in the central nervous system. Neuropeptides 36:209–220CrossRef
25.
go back to reference Wood AW, Duan C, Bern HA (2005) Insulin-like growth factor signaling in fish. Int Rev Cytol 243:215–228CrossRef Wood AW, Duan C, Bern HA (2005) Insulin-like growth factor signaling in fish. Int Rev Cytol 243:215–228CrossRef
26.
go back to reference 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 75:59–72 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 75:59–72
27.
go back to reference Harel Z, Tannenbaum GS (1995) Long-term alterations in growth hormone and insulin secretion after temporary dietary protein restriction in early life in the rat. Pediatr Res 38:747–753CrossRef Harel Z, Tannenbaum GS (1995) Long-term alterations in growth hormone and insulin secretion after temporary dietary protein restriction in early life in the rat. Pediatr Res 38:747–753CrossRef
28.
go back to reference Whitaker-Azmitia PM (2005) Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Int J Dev Neurosci 23:75–83CrossRef Whitaker-Azmitia PM (2005) Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Int J Dev Neurosci 23:75–83CrossRef
29.
go back to reference Janusonis S (2005) Serotonergic paradoxes of autism replicated in a simple mathematical model. Medl Hypotheses 64:742–750CrossRef Janusonis S (2005) Serotonergic paradoxes of autism replicated in a simple mathematical model. Medl Hypotheses 64:742–750CrossRef
30.
go back to reference Hranilovic D, Blazevic S, Ivica N, Cicin-Sain L, Oreskovic D (2011) The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats. Neurochem Int 59:202–207CrossRef Hranilovic D, Blazevic S, Ivica N, Cicin-Sain L, Oreskovic D (2011) The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats. Neurochem Int 59:202–207CrossRef
31.
go back to reference Lowry OH, Rosebrough NJ, Farr AL, Randal RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275 Lowry OH, Rosebrough NJ, Farr AL, Randal RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
32.
go back to reference Musumeci G, Carnazza M, Leonardi R, Loreto C (2012) Expression of beta-defensin-4 in “an in vivo and ex vivo model” of human osteoarthritic knee meniscus. Knee Surg Sports Traumatol Arthrosc 20:216–222CrossRef Musumeci G, Carnazza M, Leonardi R, Loreto C (2012) Expression of beta-defensin-4 in “an in vivo and ex vivo model” of human osteoarthritic knee meniscus. Knee Surg Sports Traumatol Arthrosc 20:216–222CrossRef
33.
go back to reference Loreto C, Lo Castro E, Musumeci G, Loreto F, Rapisarda G, Rezzani R, Castorina S, Leonardi R, Rusu MC (2012) Aquaporin 1 expression in human temporomandibular disc. Acta Histochem 114:744–748CrossRef Loreto C, Lo Castro E, Musumeci G, Loreto F, Rapisarda G, Rezzani R, Castorina S, Leonardi R, Rusu MC (2012) Aquaporin 1 expression in human temporomandibular disc. Acta Histochem 114:744–748CrossRef
34.
go back to reference Leonardi R, Loreto C, Talic N, Caltabiano R, Musumeci G (2012) Immunolocalization of lubricin in the rat periodontal ligament during experimental tooth movement. Acta Histochem 114:700–704CrossRef Leonardi R, Loreto C, Talic N, Caltabiano R, Musumeci G (2012) Immunolocalization of lubricin in the rat periodontal ligament during experimental tooth movement. Acta Histochem 114:700–704CrossRef
35.
go back to reference Musumeci G, Loreto C, Clementi G, Fiore CE, Martinez G (2011) An in vivo experimental study on osteopenia in diabetic rats. Acta Histochem 113:619–625CrossRef Musumeci G, Loreto C, Clementi G, Fiore CE, Martinez G (2011) An in vivo experimental study on osteopenia in diabetic rats. Acta Histochem 113:619–625CrossRef
36.
go back to reference 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) 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)
37.
go back to reference 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) 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)
38.
go back to reference Imbesi R, Castrogiovanni P (2008) Embryonic and postnatal development in experimental tryptophan deprived rats. A preliminary study. J Mol Histol 39:487–498CrossRef Imbesi R, Castrogiovanni P (2008) Embryonic and postnatal development in experimental tryptophan deprived rats. A preliminary study. J Mol Histol 39:487–498CrossRef
39.
go back to reference Blazevic S, Dolenec P, Hranilovic D (2011) Physiological consequences of perinatal treatment of rats with 5-hydroxytryptophan. Periodicum Biologorum 113:81–86 Blazevic S, Dolenec P, Hranilovic D (2011) Physiological consequences of perinatal treatment of rats with 5-hydroxytryptophan. Periodicum Biologorum 113:81–86
40.
go back to reference Duan C (1998) Nutritional and developmental regulation of insulin-like growth factors in fish. J Nutr 128:306S–314S Duan C (1998) Nutritional and developmental regulation of insulin-like growth factors in fish. J Nutr 128:306S–314S
41.
go back to reference Maki R (2010) Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J Clin Oncol 28:4985–4995CrossRef Maki R (2010) Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J Clin Oncol 28:4985–4995CrossRef
42.
go back to reference Raap D, Van de Kar L (1999) Selective serotonin reuptake inhibitors and neuroendocrine function. Life Sci 65:1217–1235CrossRef Raap D, Van de Kar L (1999) Selective serotonin reuptake inhibitors and neuroendocrine function. Life Sci 65:1217–1235CrossRef
43.
go back to reference 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 York 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 York
44.
go back to reference 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 21:45–54 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 21:45–54
45.
go back to reference Scicchitano BM, Rizzuto E, Musarò A (2009) Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY) 1:451–457 Scicchitano BM, Rizzuto E, Musarò A (2009) Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1. Aging (Albany NY) 1:451–457
Metadata
Title
Effects of high-tryptophan diet on pre- and postnatal development in rats: a morphological study
Authors
Paola Castrogiovanni
Giuseppe Musumeci
Francesca Maria Trovato
Rosanna Avola
Gaetano Magro
Rosa Imbesi
Publication date
01-02-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 1/2014
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-013-0528-4

Other articles of this Issue 1/2014

European Journal of Nutrition 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine