The relationship of rat brain weight and pituitary weight to postnatal growth after prenatal exposure to methylazoxymethanol.
Teratogens can affect body weight in various ways, but the association of brain damage with postnatal growth abnormalities suggests a role for neuroendocrine growth-controlling systems. Growth deficiencies follow methylazoxymethanol (MAM) exposure during the period when the growth hormone releasing factor (GRF) cells of the hypothalamus form, and the pattern of growth of the animals is like that of animals deficient in growth hormone. The present studies were designed to examine the growth, body proportions, brain weight, and pituitary weight of animals treated with 20 mg/kg MAM on the 13th day of gestation, a peak period for production of GRF neurons. Among the offspring, this treatment produced about 25% dwarfs (animals smaller than the smallest control of the same sex). Significantly more females than males were categorized as dwarfs. The weight effect occurred long after birth, as is characteristic of animals and humans with growth hormone deficiency. Analyses of weights over the course of development indicated that prenatal factors, rather than factors operating between birth and weaning, predicted the adult body weight of dwarfs, while both sets of factors were significant in other animals. The growth reduction was symmetrical, as would be expected if the animals were growth hormone deficient, with an 18% reduction in weight reflecting a 6% reduction in bone length. The remaining treated animals were similar to controls in absolute weight, body proportions, and rate of growth. Neither pituitary weight nor brain weight appears to play the key role in determining which animals will exhibit growth deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Rodier
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Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, NY 14642.
Kates
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D000375:Aging; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D051381:Rats; D012016:Reference Values
D000477:Alkylating Agents; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol