Endocrine mechanisms underlying the growth effects of developmental lead exposure in the rat.

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.

Peripheral endocrine and metabolic responses to centrally administered interleukin-1.

It is becoming increasingly apparent that interleukin-1 (IL-1) acts systemically and centrally to play an important role in regulating the hormonal and metabolic response to stress, infection, and trauma. The aim of this study was to observe the peripheral metabolic and endocrine responses to 15, 25, and 50 ng intracerebroventricular (i.c.v.) recombinant IL-1 beta in awake, freely moving rats over a 6-hour period. The rate and duration of elevation of temperature and plasma corticosterone and glucose were dose-dependent and did not return to control levels until 6 or more hours later. Hepatic glycogen content 6 h after i.c.v. IL-1 was 58, 52 and 78% of control after 15, 25, and 50 ng, respectively. The plasma insulin response to elevated plasma glucose in rats treated with 15 ng was absent in those treated with 25 and 50 ng. Responses of plasma glucagon to each dose of IL-1 were not significantly different from control responses. PEPCK enzyme activity was diminished to 60, 66, and 81% of control after 15, 25, and 50 ng IL-1, respectively. No changes of body temperature or plasma corticosterone were observed when 25 or 50 ng IL-1 were injected intravenously. These results are strong evidence that central actions of IL-1 significantly affect peripheral glycemia via classical hepatic and endocrine adjustments.