1 / 1

Further Studies of Estradiol and Intake of Palatable Ingesta

Further Studies of Estradiol and Intake of Palatable Ingesta Larry D Reid, Karen J Boswell, Lucas A Klein, Christopher A Caffalette, Joel E Schlosburg, Karen T Stitt, and Meta L Reid

ronna
Download Presentation

Further Studies of Estradiol and Intake of Palatable Ingesta

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Further Studies of Estradiol and Intake of Palatable Ingesta Larry D Reid, Karen J Boswell,Lucas A Klein, Christopher A Caffalette, Joel E Schlosburg,Karen T Stitt,andMeta L Reid Laboratory for Psychopharmacology, Siena College, Loudonville, NY andRensselaer Polytechnic Institute, Troy, NY,United States of America SIENA COLLEGE Fig. 1. The effects of injections on bodyweights, measured daily, are depicted for the day before (-1), the day of injections (0), and the following days (1-8). Notice that the injection of vehicle control (PL) did not disrupt ordinary rate of weight gain. The injection of 0.38 mg/kg of EV did reduce weight gain and even produced some weight loss. During the times depicted no F&S dietary supplement was presented. The females had ordinary laboratory rat-food and water available always. The assumption is made that during the period when the females are not gaining weight, as they would ordinarily, that they are experiencing a malaise or mild illness. If that is true and if we had presented F&S during those days, the further assumption is made that the pairing of these events would condition the malaise to the F&S and reduce its attractiveness. As exemplified in recent reviews (1,2), and supported by results from hundreds of studies using laboratory subjects such as female rats, the conclusion is that estradiol (when given as a drug) reduces food-intake. This conclusion is nicely balanced by observations that ovariectomies lead to weight gain. However, a different perspective emerges from our recently collected data. At previous meetings of the IBNS, we have presented data indicating that estradiol valerate (EV), a product for the extended release of estradiol, can increase intakes of alcoholic beverage, saccharin solutions, and chocolate cake mix batter. EV often decreases intakes shortly after injections. Subsequently, EV enhances the intakes of some ingesta, but not all kinds of them. EV did not enhance intakes of ordinary rat-food or a bittersweet saccharin solution. The doses of EV used with alcoholic beverages and saccharin solutions were very large. The doses that modified chocolate cake mix batter were considerably smaller. The fact that smaller doses modified intake of palatable ingesta opened many questions. A salient question is whether the estrogenic drugs taken by women might enhance appetite which, in turn, might increase the risk of obesity, and, in turn, account for the greater incidence of obesity among women compared to men (3). Procedural differences can account for why previous results and our new results differ. For example, we apply estradiol across a number of days and follow our female rats for prolonged periods (even after supraphysiological levels of estradiol are probably not extant). We have learned to minimize conditioned suppression of ingestion associated with a malaise that accompanies initial application of estradiol (see Fig. 1). We have used ingesta that tend to be taken in excess (e.g., alcoholic beverages and chocolate). Consequently, we see enduring increments in intake. Using a dose of EV that enhanced intakes of chocolate cake mix batter, we assessed its effects on intake of a mixture of fat and sugar (F&S), This dose, 0.38 mg/kg, is larger than doses that modify the events of the estrous cycle but considerably smaller than the doses (10 mg/kg) Brawer and his colleagues (4) demonstrated to be toxic to the arcuate n. of the hypothalamus. Method Sprague-Dawley female rats were delivered to the laboratory from Taconic Farms when they weighed about 190 g. They were housed individually with food and water always available. Shortly after their arrival, they were presented for 24 hr a day for 8 days a mixture of fat and sugar. The fat was nearly solid, white, vegetable shortening and the sugar was table sugar, both purchased from a local market. The ratio was 1 unit of one, in terms of volume, to 1 unit of the other. During the 8 days, all 20 of the females took considerable amounts of F&S. Two groups were formed so that their bodyweight were nearly the same and their last day’s intake of F&S was nearly the same. Then, the groups were randomly assigned to receive either EV or the vehicle for EV, sesame seed oil. F&S presentation was suspended for 8 days. Then, injections were given, intramuscularly, and produced the characteristic loss of weight associated with injections of EV. Eight days after injections F&S were introduced again. Measures of intake and of bodyweights were taken for 49 days. Results and Discussion. The results are summarized in the figures. Fig. 1 demonstrates what we see just after injections of EV: a loss of weight and a suspension of ordinary weight gain that lasts for days, followed by a return to rate of weight gain very similar to that of the controls. Fig. 2 presents the mean intake of F&S for the EV- and placebo-treated females for the 49 days of measurement. Total intake of the F&S group across the 49 days, for the EV-treated group, is 493.4; and for the placebo-treated group, is 405.9 g, p = .013. (for intakes in terms of total g/kg taken, not g, see figure caption). EV-treated females ate 22% more g of F&S than controls and gained 34% more weight (Day 49 to Day 1 comparisons) (Fig. 3). Fig. 3 presents the mean bodyweights for the 49 days. The EV group weighed nearly the same as the placebo group before injections, lost weight with injections (Fig. 1) and, therefore, started the days with F&S availability weighing less than the placebo group. They, however, ended the 49 days weighing more than the controls. The placebo controls gained considerable weight, gaining, on average, about 1.5 g a day. A comparable group not having a food supplement, starting at a similar weight (about 237 g) and living in the same environment, gained, on average, about 1.2 g a day. The EV-treated females gained, on average, 2.0 g a day. These data are contrary to the generalization that estrogenic drugs reduce food intake. Doses of EV may reduce food intake initially, but they can surely increase intakes subsequently. These data provide evidence to support the contention that the enhanced appetites that follow applications of estradiol can lead to excessive weight gain, i.e., obesity. The initial studies (5,6,7) involving injections of EV and measures of ingestion used the doses used by Brawer et al. (2 mg a female rat or about 10 mg/kg), because we were interested in the specific lesions of the arcuate n. that the large doses produced. When, however, we found that smaller doses, such as the 0.38 mg/kg used in this experiment, had a profound effect on intake of palatable ingesta, a different perspective emerged. The resulting circulating levels of estradiol are probably similar to those produced by pregnancy and are comparable to the levels that might be achieved by women who take estrogenic drugs for treating the adverse effects associated with menopause and for birth control. Notice the dramatic feature of the results. As long as F&S was available, a single dose of EV (whose effects, in terms of circulating estradiol, had probably diminished to nil) had lasting effects on weight gain that would probably extend to the point of inducing morbid obesity. Our conclusion that estradiol can enhance appetite may be applicable to women. A side-effect of estrogenic medicines, herbal supplements, and soy products may exceed a threshold for estrogenic stimulation that, in turn, enhances appetite for F&S and, thereby, increases the risk of obesity. Fig. 2. Daily intakes of F&S by two groups of female rats (n = 10 for each group) are depicted. The bars represent standard errors (SEM) of the mean. Notice that on most days, but not all, the means are two SEMs apart (statistical significance). Total intake of the F&S group across the 49 days, for the EV-treated group, is 1711.9 g/kg; and for, for the placebo-treated group, is 1448.5 g/kg, p = .021. References. 1. Eckel LA. (2004). Estradiol: a rhythmic, inhibitory, indirect control of meal size. Physiol Behav 82, 35-41.   2. Horvath TL, Diano S, Tschop M. (2004). Brain circuits regulating energy homeostasis. The Neuroscientist, 10, 235-46. 3. Flegal KM, Carroll MD, Ogden CL, Johnson CL. (2002). Prevalence and trends in obesity among US adults, 1999-2000. JAMA 288,1723-27. 4. Brawer JR, Beaudet A, Desjardins GC, Schipper HM. (1993). Pathologic effect of estradiol on the hypothalamus. Biol Reprod 49, 647-652. 5. Boswell KJ, Reid ML, FitchJV, Bennett SM, Narciso SP, HubbellCL, ReidLD. (2005). Estradiol valerate and intake of sweetened water. Pharmacol Biochem Behav, 80, 1-7. 6. Reid ML, Hubbell CL, Reid LD. (2003). A pharmacological dose of estradiol can enhance appetites for alcoholic beverages. Pharmacol Biochem Behav 2, 381-8. 7. Reid LD, Marinelli PW, Bennett SM, Fiscale LT, Narciso SP, Oparowski CJ, Reid ML, Merrigan BA, Moricone J, Hubbell CL, Gianoulakis C (2002). One injection of estradiol valerate induces dramatic changes in rats' intake of alcoholic beverages. Pharmacol Biochem & Behav 72, 601-616 Fig. 3. Mean bodyweights each day of presentation of F&S are depicted. Note that the females receiving EV weighed less than those receiving placebos initially. The EV-treated females, however, gained weight at a more rapid rate than their counterparts. Presented at the International Behavioral Neuroscience Society meeting, Santa Fe, New Mexico, USA—June 2005

More Related