Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets.

Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences.

Phase I of The National Beef Quality Audit-2011: quantifying willingness-to-pay, best-worst scaling, and current status of quality characteristics in different beef industry marketing sectors.

The National Beef Quality Audit (NBQA)-2011 benchmarked the current status of and assessed progress being made toward quality and consistency of U.S. cattle, carcasses, and beef products after the completion of the first NBQA in 1991. Unlike previous NBQA, objectives of the 2011 Phase I study were to determine how each beef market sector defined 7 quality categories, estimate willingness-to-pay (WTP) for the same quality categories by market sector, and establish a best-worst (B/W) scaling for the quality categories. Structured face-to-face interviews were conducted and responses were recorded using dynamic routing software over an 11-mo period (February to December 2011) with decision makers in each of the following beef market sectors: Feeders (n = 59), Packers (n = 26), Food Service, Distribution, and Further Processors (n = 48), Retailers (n = 30), and Government and Allied Industries (n = 47). All respondents participated in a structured interview consisting of WTP and B/W questions that were tied to 7 quality categories and then were asked to "define" each of the 7 categories in terms of what the category meant to them, resulting in completely unbiased results. The 7 quality categories were a) how and where the cattle were raised, b) lean, fat, and bone, c) weight and size, d) cattle genetics, e) visual characteristics, f) food safety, and g) eating satisfaction. Overall, "food safety" and "eating satisfaction" were the categories of greatest and second most importance, respectively, to all beef market sectors except for Feeders. Feeders ranked "how and where the cattle were raised" and "weight and size" as the most important and second most important, respectively. Overall, "how and where the cattle were raised" had the greatest odds of being considered a nonnegotiable requirement before the raw material for each sector would be considered for purchase and was statistically more important (P < 0.05) as a requirement for purchase than all other categories except "food safety." When all market sectors were considered, "eating satisfaction" was shown to generate the greatest average WTP percentage premium (11.1%), but that WTP premium value only differed statistically (P < 0.05) from "weight and size" (8.8%). Most notably, when a sector said that "food safety" was a nonnegotiable requirement, no sector was willing to purchase the product at a discounted price if the "food safety" of the product could not be assured.

National Beef Quality Audit-2011: Survey of instrument grading assessments of beef carcass characteristics.

The instrument grading assessments for the 2011 National Beef Quality Audit evaluated seasonal trends of beef carcass quality and yield attributes over the course of the year. One week of instrument grading data, HCW, gender, USDA quality grade (QG), and yield grade (YG) factors, were collected every other month (n = 2,427,074 carcasses) over a 13-mo period (November 2010 through November 2011) from 4 beef processing corporations, encompassing 17 federally inspected beef processing facilities, to create a "snapshot" of carcass quality and yield attributes and trends from carcasses representing approximately 8.5% of the U.S. fed steer and heifer population. Mean yield traits were YG (2.86), HCW (371.3 kg), fat thickness (1.19 cm.), and LM area (88.39 cm(2)). The YG distribution was YG 1, 15.7%; YG 2, 41.0%; YG 3, 33.8%; YG 4, 8.5%; and YG 5, 0.9%. Distribution of HCW was <272.2 kg, 1.6%; 272.2 to 453.6 kg, 95.1%; and ≥453.6 kg, 3.3%. Monthly HCW means were November 2010, 381.3 kg; January 2011, 375.9 kg; March 2011, 366.2 kg; May 2011, 357.9 kg; July 2011, 372.54 kg; September 2011, 376.1 kg; and November 2011, 373.5 kg. The mean fat thickness for each month was November 2010, 1.30 cm; January 2011, 1.22 cm; March 2011, 1.17 cm; May 2011, 1.12 cm; July 2011, 1.19 cm; September 2011, 1.22 cm; and November 2011, 1.22 cm. The overall average marbling score was Small(49). The USDA QG distribution was Prime, 2.7%; Top Choice, 22.9%; Commodity Choice, 38.6%; and Select, 31.5%. Interestingly, from November to May, seasonal decreases (P < 0.001) in HCW and fat thicknesses were accompanied by increases (P < 0.001) in marbling. These data present the opportunity to further investigate the entire array of factors that determine the value of beef. Data sets using the online collection of electronic data will likely be more commonly used when evaluating the U.S. fed steer and heifer population in future studies.

National Beef Quality Audit-2011: In-plant survey of targeted carcass characteristics related to quality, quantity, value, and marketing of fed steers and heifers.

The 2011 National Beef Quality Audit (NBQA-2011) assessed the current status of quality and consistency of fed steers and heifers. Beef carcasses (n = 9,802), representing approximately 10% of each production lot in 28 beef processing facilities, were selected randomly for the survey. Carcass evaluation for the cooler assessment of this study revealed the following traits and frequencies: sex classes of steer (63.5%), heifer (36.4%), cow (0.1%), and bullock (0.03%); dark cutters (3.2%); blood splash (0.3%); yellow fat (0.1%); calloused rib eye (0.05%); overall maturities of A (92.8%), B (6.0%), and C or greater (1.2%); estimated breed types of native (88.3%), dairy type (9.9%), and Bos indicus (1.8%); and country of origin of United States (97.7%), Mexico (1.8%), and Canada (0.5%). Certified or marketing program frequencies were age and source verified (10.7%), ≤A(40) (10.0%), Certified Angus Beef (9.3%), Top Choice (4.1%), natural (0.6%), and Non-Hormone-Treated Cattle (0.5%); no organic programs were observed. Mean USDA yield grade (YG) traits were USDA YG (2.9), HCW (374.0 kg), adjusted fat thickness (1.3 cm), LM area (88.8 cm2), and KPH (2.3%). Frequencies of USDA YG distributions were YG 1, 12.4%; YG 2, 41.0%; YG 3, 36.3%; YG 4, 8.6%; and YG 5, 1.6%. Mean USDA quality grade (QG) traits were USDA quality grade (Select(93)), marbling score (Small(40)), overall maturity (A(59)), lean maturity (A(54)), and skeletal maturity (A(62)). Frequencies of USDA QG distributions were Prime, 2.1%; Choice, 58.9%; Select, 32.6%; and Standard or less, 6.3%. Marbling score distribution was Slightly Abundant or greater, 2.3%; Moderate, 5.0%; Modest, 17.3%; Small, 39.7%; Slight, 34.6%; and Traces or less, 1.1%. Carcasses with QG of Select or greater and YG 3 or less represented 85.1% of the sample. This is the fifth benchmark study measuring targeted carcass characteristics, and information from this survey will continue to help drive progress in the beef industry. Results will be used in extension and educational programs as teaching tools to inform beef producers and industry professionals of the current state of the U.S. beef industry.

Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system.

AIMS: The effects of insulins detemir (Det) and glargine (Glar) on endogenous glucose production (EGP) and net hepatic glucose output (NHGO) were compared. METHODS: Arteriovenous difference and tracer ([3-(3) H]glucose) techniques were employed during a two-step hyperinsulinemic euglycaemic clamp in conscious dogs (6 groups, n = 5-6/group). After equilibration and basal sampling (0-120 min), somatostatin was infused and basal glucagon was replaced intraportally. Det or Glar was infused via portal vein (Po), peripheral vein (IV), or bilateral carotid and vertebral arteries (H) at 0.1 and 0.3 mU/kg/min (low Insulin; Glar vs. Det, respectively, 120-420 min) and 4× the low insulin rate (high insulin; 420-540 min). RESULTS: NHGO and EGP were suppressed and glucose R(d) and infusion rate were stimulated similarly by Det and Glar at both Low and high insulin with each infusion route. Non-esterified fatty acid (NEFA) concentrations during low insulin were 202 ± 37 versus 323 ± 75 µM in DetPo and GlarPo (p < 0.05) and 125 ± 39 versus 263 ± 48 µM in DetIV and GlarIV, respectively (p < 0.05). In DetH versus GlarH, pAkt/Akt (1.7 ± 0.2 vs. 1.0 ± 0.2) and pSTAT3/STAT3 (1.4 ± 0.2 vs. 1.0 ± 0.1) were significantly increased in the liver but not in the hypothalamus. CONCLUSIONS: Det and Glar have similar net effects on acute regulation of hepatic glucose metabolism in vivo regardless of delivery route. Portal and IV detemir delivery reduces circulating NEFA to a greater extent than glargine, and head detemir infusion enhances molecular signalling in the liver. These findings indicate a need for further examination of Det's central and hepatic effects.

Insulin action on the liver in vivo.

Insulin has a potent inhibitory effect on hepatic glucose production by direct action at hepatic receptors. The hormone also inhibits glucose production by suppressing both lipolysis in the fat cell and secretion of glucagon by the alpha-cell. Neural sensing of insulin levels appears to participate in control of hepatic glucose production in rodents, but a role for brain insulin sensing has not been documented in dogs or humans. The primary effect of insulin on the liver is its direct action.

Donors whose blood reacts falsely positive in transfusion microbiology screening assays need not be lost to transfusion.

Donations that repeatedly react in transfusion microbiology screening assays are usually discarded; with appropriate confirmatory testing on the index and on follow-up samples, the great majority of these can be shown to be falsely positive. Under carefully controlled conditions, with secure information transfer, these donations, although still reactive in the primary screening assays, can be made available for clinical use after testing and obtaining negative results with alternative assays from a list of assays evaluated as suitable for the release of blood donations. We will describe a generic algorithm that can be applied to all markers.

Regulation of hepatic metabolism by enteral delivery of nutrients.

The liver plays a unique role in nutrient homeostasis. Its anatomical location makes it ideally suited to control the systemic supply of absorbed nutrients, and it is the primary organ that can both consume and produce substantial amounts of glucose. Moreover, it is the site of a substantial fraction (about 25 %) of the body's protein synthesis, and the liver and other organs of the splanchnic bed play an important role in sparing dietary N by storing ingested amino acids. This hepatic anabolism is under the control of hormonal and nutritional changes that occur during food intake. In particular, the route of nutrient delivery, i.e. oral (or intraportal) v. peripheral venous, appears to impact upon the disposition of the macronutrients and also to affect both hepatic and whole-body nutrient metabolism. Intraportal glucose delivery significantly enhances net hepatic glucose uptake, compared with glucose infusion via a peripheral vein. On the other hand, concomitant intraportal infusion of both glucose and gluconeogenic amino acids significantly decreases net hepatic glucose uptake, compared with infusion of the same mass of glucose by itself. Delivery of amino acids via the portal vein may enhance their hepatic uptake, however. Elevation of circulating lipids under postprandial conditions appears to impair both hepatic and whole-body glucose disposal. Thus, the liver's role in nutrient disposal and metabolism is highly responsive to the route of nutrient delivery, and this is an important consideration in planning nutrition support and optimising anabolism in vulnerable patients.

Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse.

The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight=31+/-1.8 g versus conventionally housed body weight=41+/-2.3 g, a 25% decrease in body weight p<0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.

Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region.

UNLABELLED: Whether glucagon-like peptide-1 (GLP-1) has insulin-independent effects on glucose disposal in vivo was assessed in conscious dogs by use of tracer and arteriovenous difference techniques. After a basal period, each experiment consisted of three periods (P1, P2, P3) during which somatostatin, glucagon, insulin, and glucose were infused. The control group (C) received saline in P1, P2, and P3, the PePe group received saline in P1 and GLP-1 (7.5 pmol.kg(-1).min(-1)) peripherally (Pe; iv) in P2 and P3, and the PePo group received saline in P1 and GLP-1 peripherally (iv) (P2) and then into the portal vein (Po; P3). Glucose and insulin concentrations increased to two- and fourfold basal, respectively, and glucagon remained basal. GLP-1 levels increased similarly in the PePe and PePo groups during P2 ( approximately 200 pM), whereas portal GLP-1 levels were significantly increased (3-fold) in PePo vs. PePe during P3. In all groups, net hepatic glucose uptake (NHGU) occurred during P1. During P2, NHGU increased slightly but not significantly in all groups. During P3, NHGU increased in PePe and PePo groups to a greater extent than in C, but no significant effect of the route of infusion of GLP-1 was demonstrated (16.61 +/- 2.91 and 14.67 +/- 2.09 vs. 4.22 +/- 1.57 micromol.kg(-1).min(-1), respectively). IN CONCLUSION: GLP-1 increased glucose disposal in the liver independently of insulin secretion; its full action required long-term infusion. The route of infusion did not modify the hepatic response.

Activation of aggressive behavior by progesterone and testosterone in male tree lizards, Urosaurus ornatus.

Testosterone is usually thought to be the major sex steroid regulating adult male territorial aggression in vertebrates. However, recent evidence has suggested a role for progesterone, as well as testosterone, in the organization of the two male reproductive phenotypes of tree lizards (Urosaurus ornatus), which differ in adult levels of territorial behavior. In the present experiment we tested whether progesterone and testosterone could also play an activational role in the expression of adult aggressive behavior. We subjected post-reproductive male tree lizards to the following treatments: sham surgery, castration, castration with progesterone supplementation, and castration with testosterone supplementation. We measured several different dimensions of aggressive behavior. Overall in these post-reproductive animals, the level of aggression from lowest to highest was: castrates, shams, progesterone-treated, and testosterone-treated. Although testosterone appears to be the more potent regulator of aggressive behavior, progesterone enhanced several measures of aggression suggesting that it could play a role in natural regulation of aggressive behavior. This initial study used very high levels of progesterone (similar to or above those experienced by hatchlings) to maximize the probability of detecting an effect. Further studies are needed to determine if natural adult progesterone levels are sufficiently high to influence aggressive behavior.

Temporal patterns of limbic monoamine and plasma corticosterone response during social stress.

Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal serotonergic activity is much more rapid than one hour. To elucidate early stress responsiveness, adult male A. carolinensis were divided into four groups: isolated controls, and pairs of males sampled after 10, 20 or 40 minutes of aggressive interaction. Development of dominant-subordinate relationships was determined by behavior and by the celerity of eyespot darkening. Serotonergic activity in the hippocampus, nucleus accumbens and amygdala was elevated rapidly and equally in both dominant and subordinate males, as were plasma corticosterone concentrations. Serotonergic activity remained elevated through 40 minutes in hippocampus and nucleus accumbens. Only subordinate males had elevated corticosterone levels at 40 minutes. Social status does not impede socially induced stress responses. Rather, rapid regulation of serotonergic stress responses appears to be a mediating factor in determining both behavioral output and social status. Temporal expressions of monoaminergic and endocrine stress responses are distinctive between males of dominant and subordinate social status. Such temporal patterns of transmitter and glucocorticoid activity may reflect neurocircuitry adaptations that result in behavior modified to fit social status.

Effect of captivity in semi-natural enclosures on the reproductive endocrinology of female lizards.

Long-term captivity can result in abnormal behavior and physiology in many vertebrates. Here, we examine whether semi-natural, outdoor captive environments can offer a compromise, allowing much of the experimental control afforded by captivity, while providing the environmental conditions essential for normal behavior and physiology. We first determined plasma concentration of the sex steroid hormones progesterone, testosterone, and estradiol of free-ranging female striped plateau lizards (Sceloporus virgatus) throughout the reproductive season, and second, compared the results to those from conspecific females maintained in semi-natural outdoor enclosures. Among free-ranging females, levels of progesterone and estradiol were elevated during vitellogenesis, with an apparent surge in progesterone and testosterone occurring in association with ovulation. Following ovulation, estradiol fell to non-reproductive levels while progesterone remained elevated during the month-long period of gravidity. Long-term captivity in outdoor enclosures did not significantly affect progesterone or estradiol levels at any stage of the reproductive cycle, and did not affect testosterone levels during normal ovarian development and gravidity. However, (1) females with delayed oviposition in captivity had lower testosterone levels than free-ranging females with normal oviposition, and (2) when all females sampled were post-reproductive, captive females continued to have lower testosterone levels than free-ranging females. Thus, the endocrine response to captivity may be greater among post-reproductive females than among reproductive females. Our results are in marked contrast to many studies that show captivity can dramatically impair reproduction of female vertebrates.

Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes.

OBJECTIVE: In normal adults, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to a glucose load, especially in those with the poorest glucose tolerance. We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Five adults with type 2 diabetes underwent an oral glucose tolerance test (OGTT) on two separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose (OGTT + F or OGTT - F), in random order. Arterialized blood samples were collected from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward. RESULTS: The area under the curve (AUC) of the plasma glucose response was reduced by fructose administration in all subjects; the mean AUC during the OGTT + F was 14% less than that during the OGTT - F (P < 0.05). The insulin AUC was decreased 21% with fructose administration (P = 0.2). Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50% of that observed during the OGTT + F (P < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs. CONCLUSIONS: Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes, and this effect is not a result of stimulation of insulin secretion.

Plasma steroid-binding globulin mediation of differences in stress reactivity in alternative male phenotypes in tree lizards, Urosaurus ornatus.

Plasma steroid-binding globulins, for example, corticosteroid-binding globulin and sex hormone-binding globulin (SHBG), have been identified in a number of vertebrates. One possible function of these proteins is to regulate the amount of steroid delivery to target tissues, as only free steroids are believed to diffuse from the circulation to target cells. Male tree lizards, Urosaurus ornatus, exhibit alternative male reproductive tactics correlated with dewlap (throat-fan) coloration. Males with orange-blue dewlaps are aggressive and territorial, whereas males with orange dewlaps are less aggressive and employ a satellite strategy. The two types of males have similar basal levels of total plasma corticosterone and testosterone. However, testosterone levels of nonterritorial males are more sensitive than those of territorial males to negative regulation by stress-induced increases in corticosterone. We tested the hypothesis that this difference in corticosterone feedback on testosterone could be mediated, in part, by differences in binding globulin levels between the two types of males. We have identified two steroid-binding globulins in male tree lizards. The first binds androgens and estradiol with high affinity (10(-9) M) and is similar to previously described sex hormone-binding globulins. The second binds both androgens and C(21) steroids, such as progesterone and corticosterone, with higher specificity than estradiol and is best described as an androgen-glucocorticoid-binding globulin (AGBG). In both types of males, the capacity of AGBG is much higher than SHBG. In addition, AGBG capacity is significantly greater in territorial than nonterritorial males, whereas the capacity of SHBG does not differ between the two types of males. Calculations of free steroid levels based on the affinity and capacity measures suggest that although most testosterone circulates bound to binding globulins, binding capacity is high enough that binding globulins are also able to bind to other steroids such as corticosterone. Thus, differences in binding capacity between the two types of males could result in higher levels of free corticosterone in nonterritorial males than in territorial males, especially during stress-induced increases in corticosterone, and may explain why testosterone levels of nonterritorial males are more sensitive to negative feedback by corticosterone.

Nonhepatic response to portal glucose delivery in conscious dogs.

The glycemic and hormonal responses and net hepatic and nonhepatic glucose uptakes were quantified in conscious 42-h-fasted dogs during a 180-min infusion of glucose at 10 mg. kg(-1). min(-1) via a peripheral (Pe10, n = 5) or the portal (Po10, n = 6) vein. Arterial plasma insulin concentrations were not different during the glucose infusion in Pe10 and Po10 (37 +/- 6 and 43 +/- 12 microU/ml, respectively), and glucagon concentrations declined similarly throughout the two studies. Arterial blood glucose concentrations during glucose infusion were not different between groups (125 +/- 13 and 120 +/- 6 mg/dl in Pe10 and Po10, respectively). Portal glucose delivery made the hepatic glucose load significantly greater (36 +/- 3 vs. 46 +/- 5 mg. kg(-1). min(-1) in Pe10 vs. Po10, respectively, P < 0.05). Net hepatic glucose uptake (NHGU; 1.1 +/- 0. 4 vs. 3.1 +/- 0.4 mg. kg(-1). min(-1)) and fractional extraction (0. 03 +/- 0.01 vs. 0.07 +/- 0.01) were smaller (P < 0.05) in Pe10 than in Po10. Nonhepatic (primarily muscle) glucose uptake was correspondingly increased in Pe10 compared with Po10 (8.9 +/- 0.4 vs. 6.9 +/- 0.4 mg. kg(-1). min(-1), P < 0.05). Approximately one-half of the difference in NHGU between groups could be accounted for by the difference in hepatic glucose load, with the remainder attributable to the effect of the portal signal itself. Even in the absence of somatostatin and fixed hormone concentrations, the portal signal acts to alter partitioning of a glucose load among the tissues, stimulating NHGU and reducing peripheral glucose uptake.

Pharmacological adrenalectomy with mitotane.

The potential of mitotane (ortho, para'-DDD, commonly used to treat adrenal carcinomas in humans and dogs) was investigated as an alternative to surgical adrenalectomy in birds, salamanders, and lizards. House sparrows (Passer domesticus) were injected twice daily with vehicle or one of two doses of mitotane (225 or 450 mg/kg), and basal and stress-induced levels of corticosterone (CORT) were measured 3 and 5 days after injections. Mitotane reduced basal CORT levels to nondetectable and abolished stress-induced CORT increases by the 3rd day of treatment. In another study, a single injection of mitotane was effective in lowering endogenous CORT levels 36 h later, but levels had apparently recovered by 10 days after the injection. Mitotane did not effect testicular weights and had no detectable effect on testosterone levels. In contrast to its effects on house sparrows, mitotane did not lower endogenous CORT levels in either tiger salamanders (Ambystoma tigrinum) or tree lizards (Urosaurus ornatus), even at doses much higher than those used in house sparrows.