Alcohol is a teratogen known to cause extensive damage to the brain, yet its effects on the neuroendocrine control of growth and reproduction have not been investigated. The hypothesis that the hypothalamic-pituitary axis may be injured by prenatal exposure is supported only by evidence of postnatal growth deficiencies in human and animal FAS, and by a few reports of delays or changes in sexual maturation, but a vigorous test of the hypothesis is warranted, because endocrine deficiencies are treatable, unlike most of the symptoms of prenatal injury. Using a different teratogen, we have demonstrated changes in the hypothalamus and pituitary, and in the postnatal growth rate of rats exposed in utero. Based on these studies, and studies of the hypothalamic control of the reproductive system, we propose to compare offspring of rats exposed to chronic 35% ethanol-derived calories with isocaloric controls on the following measures: a) The number of growth hormone releasing factor (GRF) neurons, somatotropin release inhibiting factor (SRIF) neurons, and the number of luteinizing hormone releasing hormone (LHRH) neurons in the hypothalamus. The number and activity of these cells is related to the pituitary release of growth hormone, luteinizing hormone, and follicle stimulating hormone. b) The size and immunohistochemical composition of the anterior pituitary, where the somatotropic and gonadotrophic cells produce their hormones. c) The average circulating levels of growth hormone an luteinizing hormone, and the response of each to stimulation of the pituitary. d) The pattern of postnatal growth from birth to 60 days. e) The age of puberty, as judged by vaginal patency and estrous cyclicity in females, and by testis descent in males. f) The histological development of the male and female gonad at 4, 35, and 60 days. While these measures will not assay every way in which the systems could be deficient, they will evaluate the most likely symptoms and sources of endocrine disturbances, filling a crucial gap in the FAS literature, and, perhaps, suggesting clinical solutions to some features of the syndrome.
| Rodier, P M; Ingram, J L; Tisdale, B et al. (1997) Linking etiologies in humans and animal models: studies of autism. Reprod Toxicol 11:417-22 |
| Rodier, P M; Ingram, J L; Tisdale, B et al. (1996) Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. J Comp Neurol 370:247-61 |
| Rodier, P M (1995) Developing brain as a target of toxicity. Environ Health Perspect 103 Suppl 6:73-6 |
| Gavin, C E; Kates, B; Hoffman, G E et al. (1994) Changes in the reproductive system following acute prenatal exposure to ethanol or methylazoxymethanol in the rat: I. Effects on immunoreactive LHRH cell number. Teratology 49:13-9 |
| Gavin, C E; Kates, B; Gerken, L A et al. (1994) Patterns of growth deficiency in rats exposed in utero to undernutrition, ethanol, or the neuroteratogen methylazoxymethanol (MAM). Teratology 49:113-21 |
