title: Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat.
abstract: A dose-response study was conducted to examine the growth suppression associated with developmental lead exposure in a rat model and to determine the endocrine mechanisms underlying these effects. Ad libitum intake of lead acetate (0.05% to 0.45% w/v) was initiated in time-impregnated female Sprague-Dawley rats (n = 10-15/group) at gestational day 5. At birth, pups were culled to four male and four females per litter. Lead exposure of dams continued until weaning, following which lead exposure of pups was continued until sacrifice at age 2 , 35, 55, and 85 days. Birth weight and prepubertal and pubertal growth rates were significantly suppressed. Growth rates were suppressed to a much greater degree in male as compared to female pups. Decreased growth rates were accompanied by a significant decrease in plasma insulin-like growth factor 1 (IGF1) concentrations and (1) a significant increase in pituitary growth hormone (GH) content during puberty in pups of both sexes, (2) a delay in the developmental profiles of the GH-dependent male-specific liver enzymes cytochrome P-450 CYP2C11 and N-hydroxy-2-acetylaminofluorene sulfotransferase, and (3) continued suppression of these enzymes in lead-exposed adult male pups. In addition, significant decreases in plasma sex steroids, testosterone (male) and 17beta-estradiol (female), were observed during puberty. Postpuberty, at age 85 d, both IGF1 and sex steroid levels were indistinguishable from control pups despite continued lead exposure. Growth rates were also similar in control and lead-exposed pups between age 57 and 85 d. Data suggest that the mechanism underlying lead-induced sex-independent suppression of growth observed in these studies involves disruption of GH secretion during puberty. It is possible that the mechanisms underlying the greater suppression of somatic growth observed at puberty in lead-exposed male offspring may be due to the additional hypoandrogenization produced by the action of lead on the hypothalamic-pituitary-testicular axis.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock 72205, USA. RonisMartinJ@exchange.uams.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: T M
authors.initials: TM
authors.lastname: Badger
authors.forename: S J
authors.initials: SJ
authors.lastname: Shema
authors.forename: P K
authors.initials: PK
authors.lastname: Roberson
authors.forename: L
authors.initials: L
authors.lastname: Templer
authors.forename: D
authors.initials: D
authors.lastname: Ringer
authors.forename: P E
authors.initials: PE
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000187:drug effects* / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000254:growth & development
chemical_list: D007854:Lead; D013006:Growth Hormone