Gestational nicotine exposure alone or in combination with ethanol down-modulates offspring immune function.

Prenatal nicotine exposure has been shown to disrupt the development of a number of peripheral organs. In the current study, we examined the effects of gestational nicotine exposure, alone or in combination with ethanol exposure, on offspring immune function. Timed pregnant rats were treated with either nicotine (6 mg/kg/day) from gestation day 4-20 using subcutaneously implanted osmotic mini-pumps or ethanol administered in the drinking water (15% w/v) from gestation day 10-20. The combined exposure group received both treatments. The ability of offspring T and B cells to proliferate in response to nonspecific stimulation by Concanavalin A or lipopolysaccharide, respectively, was determined on postnatal days 9, 15, 22, 29, 64, and 86. Offspring splenocyte beta(2)-adrenoceptor binding was also measured. Nicotine or nicotine+ethanol suppressed splenocyte responsiveness to Concanavalin A or lipopolysaccharide which was similar in timing and magnitude to that seen with ethanol alone. Splenocytes from these groups remained subresponsive to stimulation well into adulthood. The combined drug treatment caused an overall reduction in spleen beta-adrenergic receptor binding whereas the individual drug treatments did not alter the development of spleen beta-adrenergic receptors.Our results indicate that prenatal nicotine exposure can cause long-term suppression of the proliferative response of offspring immune cells. Moreover, the effects of nicotine+ethanol may cause more severe deficits in adulthood.

Chronic and acute prenatal and postnatal ethanol exposure on lymphocyte subsets from offspring thymic, splenic, and intestinal intraepithelial sources.

The overall objective of this study was to analyze the effects of a combined prenatal and postnatal (entire gestational human chronic drinking model) ethanol exposure on T-cell development in mice. Specifically, this study evaluated the effects of chronic exposure to prenatal ethanol on lymphocyte makeup and proliferative capabilities of postnatal offspring's (4 and 12 weeks) peripheral lymphoid tissues. Chronic exposure regimens were conducted over the entire gestational period and through postnatal day 14 or 21. Thymus, spleen, and intestinal intraepithelial lymphocytes were harvested and analyzed by flow cytometry for percentages of T-cell subsets. Splenic lymphocytes were also analyzed for their ability to proliferate in response to a T-cell mitogen. Limited effects of chronic ethanol exposure were seen.

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 1.

Acute pretreatment of ovariectomized rats with genistein (G) alters gonadotropin-releasing hormone-(GnRH)-induced LH secretion in a fashion comparable to estradiol (E2). In the present studies we wished to (A) determine whether G can acutely inhibit tonic LH secretion by oral (po) or intravenous (iv) routes, (B) compare GnRH-induced LH responses following higher iv dose pretreatments with G or E2, and (C) determine effects of G or E2 pretreatments on progesterone (P)-induced secretion of LH. Mature Charles River CD rats were ovariectomized, and 2 to 5 weeks later intraatrial cannulae were placed. Serial blood samples were drawn and LH was measured by RIA. In experiments 1 and 2, G or E2 was administered acutely by gavage or iv, while in experiment 3, G and E2 were given subcutaneously (sc) oil 3 days prior to cannulation and sampling. Acute po administration of vehicle or G (0.1, 1.0, and 10 mg/kg BW) had no effect on tonic LH, while E2 suppressed LH at all doses (0.1, 1.0, and 10 mg/kg BW). Acute iv administration of vehicle and higher doses of G (1 and 10 mg/kg BW) had no effect on tonic LH, while the lowest dose G (0.1 mg/kg BW) and all doses of E2 (0.1, 1, and 10 mg/kg BW) suppressed tonic LH. In the iv-treated rats, GnRH-induced LH secretion was more profoundly suppressed by G at all doses than by E2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 2.

Acute intravenous administration of the phytoestrogen genistein (G) blocks the gonadotropin-releasing hormone-(GnRH)-induced rise of luteinizing hormone (LH) in ovariectomized rats. The present experiments were performed to determine whether subacute administration of G or the mycoestrogens zearalenone and zearalenol would affect GnRH-induced or progesterone-induced LH secretion in ovariectomized rats. Charles River CD rats were ovariectomized and used 2 to 5 weeks later. Blood samples were obtained either via decapitation or via intraatrial cannulae three days after compounds were injected subcutaneously in sesame oil or corn oil vehicle. LH was measured by RIA. Pretreatment with estradiol benzoate suppressed LH levels at 1200 h, while G had no effect. Challenge with progesterone (8 mg/kg BW, sc) evoked LH release at 1600 h in rats pretreated with estradiol benzoate, but LH levels did not change in rats pretreated with G, zearalenone, or zearalenol. While GnRH-induced LH secretion was preserved in rats pretreated with estradiol, no LH response was detected in rats pretreated with the higher dose of G (8 mg/kg BW) or either dose of zearalenol (0.8 mg/kg BW or 8 mg/kg BW). We conclude that in the ovariectomized rat 1) subacute administration of G, zearalenone, or zearalenol do not inhibit tonic LH secretion, 2) G, zearalenone, and zearalenol do not provide "estrogenic priming" for progesterone-induced LH secretion; however, 3) G and zearalenol do block GnRH-induced LH secretion. The seemingly selective neuroendocrine effects of these naturally-occurring dietary estrogens emphasize that actions of each putative estrogen must be characterized for each "estrogenic" endpoint.