ETHANOL BLOCKS THE CENTRAL ACTION OF IGF-1 TO INDUCE LUTEINIZING HORMONE SECRETION IN THE PREPUBERTAL FEMALE RAT
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Insulin-like growth factor-1 (IGF-1) is emerging as a signal of peripheral origin capable of acting centrally to induce luteinizing hormone (LH) secretion and accelerate the initiation of female puberty. Since we have shown previously that ethanol (ETOH) can suppress prepubertal LH release and delay female puberty, we hypothesized that these detrimental effects might be due, at least in part, to the drugs ability to alter the central actions of IGF-1. Thus, we have investigated the effects of ETOH on IGF-1 induced LH release in vivo, and on IGF-1 induced prostaglandin-E2 (PGE2) and LH-releasing hormone (LHRH) release in vitro from rats during the juvenile phase of development as well as from rats during the early stage of first proestrus. For the in vivo experiment three initial jugular blood samples were taken at 10-min. intervals from all rats, then the animals received either a 3g/Kg dose of ETOH or an equal volume of saline by gastric gavage. The rats were subsequently left undisturbed for 90 min. to allow time for ETOH absorption, then a single blood sample was drawn from each rat. Finally, IGF-1 (200 ng/3 microl) was microinjected into the third ventricle of all animals and five more blood samples were withdrawn at 10 min. intervals. We demonstrated that IGF-1 induced the release of LH (p<0.01) in the saline controls from rats in both phases of pubertal development. Conversely, this effect of IGF-1 was blocked by ETOH in both developmental groups. For the in vitro experiment, median eminences (MEs) were dissected, then incubated in the presence or absence of ETOH (50 mM). The amount of PGE2 and LHRH released was measured from the same samples following the addition of IGF-1 (100 ng/ml). As above, similar responses were observed from rats in both developmental phases. IGF-1 stimulated the release of PGE2 (p<0.001) and LHRH (p<0.01) from the incubated nerve terminals in the absence of ETOH; however, these effects were blocked by the presence of ETOH. Thus, these combined in vivo and in vitro results suggest that ETOH can acutely block IGF-1 induced LH release during the juvenile-peripubertal transition period, and that this is a centrally mediated action which is due to the diminished formation of PGE2 resulting in decreased LHRH release.
author list (cited authors)
Hiney, J. K., Srivastava, V., Lara, T., & Dees, W. L.
complete list of authors
Hiney, JK||Srivastava, V||Lara, T||Dees, WL