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Human Reproduction, Vol. 14, No. 8, 2155-2161, August 1999
© 1999 European Society of Human Reproduction and Embryology

Tryptophan ingestion by pregnant rats induces pituitary and mammary tumours in the adult female offspring

Cristo Santana1, Lorenzo Martin2, Francisco Valladares3, Lucio Diaz-Flores3, Celsa Santana-Herrera2, Antonio Milena4 and Manuel Rodríguez Díaz2,5

1 Department of Psychobiology of the School of Psychology, University of La Laguna, Tenerife, and Laboratory of Neurobiology and Experimental Neurology; Departments of 2 Physiology and 3 Anatomy and Pathology of the School of Medicine and 4 University Hospital of Canary Islands, Canary Islands, Spain

The present study was designed to evaluate the long-term consequences of tryptophan treatment on the central serotonergic activity in the female offspring of rats, and particularly on serotonin-controlled hormone release. During the second half of gestation, tryptophan (200 mg/kg/day) was given daily by stomach intubation to pregnant rats and the brain concentrations of serotonin and 5-hydroxyindole acetic acid and the plasma concentrations of prolactin, progesterone, oestradiol and luteinizing hormone were quantified in the adult female offspring. The offspring showed an increase in hypothalamic serotonin and serum progesterone and prolactin. In addition, maternal ingestion of tryptophan induced a marked rise in 665-day-old offspring in the incidence of both pituitary prolactinomas (62%) and mammary adenomas (49%). Present data suggest that tryptophan regulates serotonergic differentiation during early development. A transitory modification of the tryptophan concentration in the fetal brain induces a permanent increase in hypothalamic serotonin level and, in addition to modifying the release of prolactin, increases the incidence of tumours in the hypophysis and mammary gland.

Key words: adenoma/prolactin/prolactinoma/serotonin/tryptophan

5 To whom correspondence should be addressed at: Departamento de Fisiología, Facultad de Medicina, Universidad de La Laguna, 38320 Tenerife, Canary Islands, Spain


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