Uterine Metab & Body Temp in Decidualized Pseudopreg: Dex Reproduct Therapy: Rat

Spencer, Fitzgerald

Abstract

The mechanism whereby the glucocorticoids can promote resistance to the stimulatory effects of growth factors in target tissues remain unknown and generally confined to uncertainty. In this regard, studies conducted by Rabin et al., 1990 have indicated that such mechanisms may function by the production of intracellular proteins which regulate the steps involved in signal transduction form the growth factor receptors. Hence the specific aim of the project will be to investigate whether there are possible broad avenues through which the synthetic glucocorticoid (DEX) could be involved in the inhibition of cellular and biological functions during reproduction. The proposed investigation will incorporate two aspects: 1. the more specific uterine metabolism during decidualized pseudopregnancy (DCPG); and 2. the more general body temperature rhythm during this reproductive tenure. While employing the albino rat as a mammalian model, the studies will be focused on the post-implantational period (Days 5-12 DCPG) which is critical for embryonic development and fetal organogenesis. Also the time-dependent administration of DEX will also be studied. This will help to clarify the circadian effectiveness of the treatment. Consequently, the hypotheses to be tested are as follows: Firstly, whether DEX, a synthetic glucocorticoid, can adversely influence DCPG (a possible anti-deciduogenic action). This will be accomplished by studying the growth of the decidualized uterus following its stimulation on Day 4 DCPG. In this regard the levels of uterine protein and glycogen will be employed as endpoints for the possible antagonistic activity of DEX on uterine growth. Uterine progesterone content, plus cytosolic and nuclear progesterone and estrogen receptor measurements should shed some light on uptake/receptor interactive involvement. Secondly, whether DEX can negatively interrupt the more general body temperature function during DCPG will also be ascertained. The endpoints to be tested whether the time-related treatment (a possible chronotoxic effect) with DEX is of any importance in biological responsiveness and/or sensitivity will constitute a point which will also be tested.