Hierarchies in the energy budget: Thyroid hormones and the evolution of human life history patterns.

The evolution of human life history characteristics required dramatic shifts in energy allocation mechanisms compared with our primate ancestors. Thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3), are sensitive to energy balance, and are significant determinants for both tissue-specific and whole-body metabolic rate. Thus, thyroid hormones are in part responsible for setting the body's overall energy budget and likely played an important role in the evolution of human life history patterns. We propose that the dynamics of mammalian T3 production, uptake, and action have evolved so that energy allocation prioritizes the high demands of brain development and functioning, often at the expense of growth and reproduction. This paper explores the role of thyroid hormone dynamics in the evolution of human encephalization, prolonged childhood and adolescence, long lifespans, reproduction, and human aging.

To the extreme! How biological anthropology can inform exercise physiology in extreme environments.

The fields of biological anthropology and exercise physiology are closely related and can provide mutually beneficial insights into human performance. These fields often use similar methods and are both interested in how humans function, perform, and respond in extreme environments. However, these two fields have different perspectives, ask different questions, and work within different theoretical frameworks and timescales. Biological anthropologists and exercise physiologists can greatly benefit from working together when examining human adaptation, acclimatization, and athletic performance in the extremes of heat, cold, and high-altitude. Here we review the adaptations and acclimatizations in these three different extreme environments. We then examine how this work has informed and built upon exercise physiology research on human performance. Finally, we present an agenda for moving forward, hopefully, with these two fields working more closely together to produce innovative research that improves our holistic understanding of human performance capacities informed by evolutionary theory, modern human acclimatization, and the desire to produce immediate and direct benefits.

Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study.

Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

Brown adipose tissue thermogenesis among young adults in northeastern Siberia and Midwest United States and its relationship with other biological adaptations to cold climates.

OBJECTIVES: Recent research suggests that brown adipose tissue (BAT) plays a functional role in non-shivering thermogenesis; however, few studies have examined population variation in BAT or its relationship with other mechanisms of adaptation to cold stress. This study characterized BAT thermogenesis and other adaptive responses to low temperatures among Indigenous Siberian young adults and young adults living near Chicago, IL. MATERIALS AND METHODS: We recruited 72 Yakut participants (42 females; 30 males) and 54 participants in Evanston, IL (40 females; 14 males). Anthropometric dimensions and resting metabolic rate (RMR) were measured, and we calculated percent divergence in RMR from expected values (divRMR). We also quantified change in supraclavicular temperature, sternum temperature, and energy expenditure after a mild cooling condition. RESULTS: Participants in Yakutia were less likely to shiver during the cooling condition (p < .05) and exhibited significantly greater evidence of BAT thermogenesis, warmer sternum temperatures, and higher divRMR than participants in Evanston (p < .05). Additionally, the relationship between change in supraclavicular temperature and energy expenditure differed between the two samples. CONCLUSIONS: Yakut young adults displayed greater evidence of BAT thermogenesis in response to mild cooling compared with young adults living near Chicago, IL. Furthermore, the relationship between BAT thermogenesis and change in energy expenditure appears to be stronger among Yakut adults. Adults that exhibited greater metabolic response to cold stress, such as higher BAT thermogenesis and divRMR, maintained warmer sternum temperatures. These results highlight the degree to which adaptation to cold climates involves multiple integrated biological pathways.

The evolutionary significance of human brown adipose tissue: Integrating the timescales of adaptation.

While human adaptability is regarded as a classical topic in anthropology, recent work provides new insight into metabolic adaptations to cold climates and the role of phenotypic plasticity in human evolution. A growing body of literature demonstrates that adults retain brown adipose tissue (BAT) which may play a role in non-shivering thermogenesis. In this narrative review, we apply the timescales of adaptation framework in order to explore the adaptive significance of human BAT. Human variation in BAT is shaped by multiple adaptive modes (i.e., allostasis, acclimatization, developmental adaptation, epigenetic inheritance, and genetic adaptation), and together the adaptive modes act as an integrated system. We hypothesize that plasticity in BAT facilitated the successful expansion of human populations into circumpolar regions, allowing for selection of genetic adaptations to cold climates to take place. Future research rooted in human energetics and biocultural perspectives is essential for understanding BAT's adaptive and health significance.

Feasibility of using infrared thermal imaging to examine brown adipose tissue in infants aged 18 to 25 months.

BACKGROUND: Recent studies in adults indicate that cold-induced temperature change of supraclavicular skin corresponds with brown adipose tissue (BAT) thermogenesis. AIM: This study examined the feasibility of using thermography to assess temperature changes in infants aged 18-25 months after mild cooling. Further, this study sought to evaluate whether cold exposure induces a thermal response suggestive of BAT activity underlying the supraclavicular region. SUBJECTS AND METHODS: Changes in maximum skin temperature at the supraclavicular and interscapular regions were determined using thermal imaging following a mild 5-minute cooling condition (by removal of clothes in a climate-controlled room) in 67 Samoan infants. Temperature changes of the forehead and hand, known BAT-free regions, served as indicators of cooling efficacy. RESULTS: Infants with increased hand and forehead temperatures after cold exposure were excluded from analysis, reducing the effective sample size to 19 infants. On average, forehead (p < 0.001), hand (p < 0.001) and back (0.029) temperatures dropped significantly while supraclavicular temperatures remained constant. Participants with greater decreases in forehead temperature tended to exhibit greater supraclavicular thermogenesis (p = 0.084), suggesting potential BAT activity in this region. CONCLUSIONS: While further work is necessary to develop a reliable cooling condition, this study provides proof-of-concept for non-invasive assessment of BAT activity in infants.

Evidence for a sensitive period of plasticity in brown adipose tissue during early childhood among indigenous Siberians.

OBJECTIVES: Evolutionary theorists have debated the adaptive significance of developmental plasticity in organisms with long lifespans such as humans. This debate in part stems from uncertainty regarding the timing of sensitive periods. Does sensitivity to environmental signals fluctuate across development or does it steadily decline? We investigated developmental plasticity in brown adipose tissue (BAT) among indigenous Siberians in order to explore the timing of phenotypic sensitivity to cold stress. METHODS: BAT thermogenesis was quantified using infrared thermal imaging in 78 adults (25 men; 33 women). Cold exposure during gestation, infancy, early childhood, middle childhood, and adolescence was quantified using: (1) the average ambient temperature across each period; (2) the number of times daily temperature dropped below -40°F during each period. We also assessed past cold exposure with a retrospective survey of participation in outdoor activities. RESULTS: Adult BAT thermogenesis was significantly associated with the average temperature (p = 0.021), the number of times it was below -40°F (p = 0.026), and participation in winter outdoor activities (p = 0.037) during early childhood. CONCLUSIONS: Our results suggest that early childhood represents an important stage for developmental plasticity, and that culture may play a critical role in shaping the timing of environmental signals. The findings highlight a new pathway through which the local consequences of global climate change may influence human biology, and they suggest that ambient temperature may represent an understudied component of the developmental origins of health and disease.

Intersecting vulnerabilities in human biology: Synergistic interactions between climate change and increasing obesity rates.

OBJECTIVES: Increasing obesity rates and accelerating climate change represent two global health challenges shaped by lifestyle change and human environmental modifications. Yet, few studies have considered how these issues may interact to exacerbate disease risk. METHODS: In this theory article, we explore evidence that obesity-related disease and climatic changes share socio-ecological drivers and may interact to increase human morbidity and mortality risks. Additionally, we consider how obesity-climate change interactions may disproportionately affect vulnerable populations and how anthropological research can be applied to address this concern. RESULTS: Interactions between heat stress and cardiometabolic disease represent an important pathway through which climate change and obesity-related morbidities may jointly impair health. For example, individuals with higher body fatness and obesity-related metabolic conditions (eg, type 2 diabetes) exhibit a reduced ability to dissipate heat. The risk of poor health resulting from these interactions is expected to be heterogeneous, with low- and middle-income countries, individuals of lower socioeconomic status, and minority populations facing a greater disease burden due to relative lack of resource access (eg, air conditioning). Moreover, older adults are at higher risk due to aging-associated changes in body composition and loss of thermoregulation capabilities. CONCLUSIONS: Few policy makers appear to be considering how interventions can be designed to simultaneously address the medical burden posed by increasing obesity rates and climate change. Anthropological research is well situated to address this need in a nuanced and culturally-sensitive way; producing research that can be used to support community resilience, promote holistic well-being, and improve health outcomes.

Covid-19 lockdowns, income distribution, and food security: An analysis for South Africa.

Absent vaccines and pharmaceutical interventions, the only tool available to mitigate its demographic effects is some measure of physical distancing, to reduce contagion by breaking social and economic contacts. Policy makers must balance the positive health effects of strong distancing measures, such as lockdowns, against their economic costs, especially the burdens imposed on low income and food insecure households. The distancing measures deployed by South Africa impose large economic costs and have negative implications for the factor distribution of income. Labor with low education levels are much more strongly affected than labor with secondary or tertiary education. As a result, households with low levels of educational attainment and high dependence on labor income would experience an enormous real income shock that would clearly jeopardize the food security of these households. However, in South Africa, total incomes for low income households are significantly insulated by government transfer payments. From public health, income distribution and food security perspectives, the remarkably rapid and severe shocks imposed because of Covid-19 illustrate the value of having in place transfer policies that support vulnerable households in the event of 'black swan' type shocks.

Brown adipose tissue and type 2 diabetes.

Recent work proposes that a regimen of repeated mild cold exposure may have protective effects against the development of type II diabetes mellitus (T2D) by activating brown adipose tissue (BAT) metabolism. BAT may protect against by increasing whole-body energy expenditure and insulin sensitivity. An evolutionary perspective, however, highlights several limitations of this hypothesis. Some individuals adapt to acute cold stress by constricting their blood vessels, which leads to high blood pressure. Thus, a regimen of repeated mild cooling may have beneficial health effects for some individuals and negative consequences for others. Future research should examine the relationships between low temperature exposure, BAT metabolism, blood pressure, and type II diabetes risk.

Field and laboratory methods for quantifying brown adipose tissue thermogenesis.

Non-shivering thermogenesis (NST) is a metabolic response to acute cold exposure that involves the liberation of chemical energy through physiological mechanisms that are separate from muscle shivering. Recent research suggests that the metabolic and endocrine action of brown adipose tissue (BAT) may play an important role in adult human NST. Thus, characterizing variation in BAT across human populations is of central importance to human biologists interested in human energetics and cardio-metabolic health. The gold standard for measuring BAT requires positron emission tomography (PET) and computed tomography (CT)-a technique that is expensive, exposes the participant to radiation, and is inaccessible to researchers working in many regions. Here, the author outline a noninvasive, portable alternative approach to quantifying BAT that modifies the protocols commonly used in PET/CT studies. The method consists of three components: (a) activating BAT thermogenesis using a mild cooling condition; (b) indirectly quantifying BAT thermogenesis by measuring the change in skin temperature where BAT is commonly stored using infrared thermal imaging; and (c) estimating NST by measuring the change in energy expenditure using open-circuit indirect calorimetry. The development of "field-friendly" methods will allow human biologists to better characterize population variation in BAT as well as its adaptive and health significance.

Brown adipose tissue, energy expenditure, and biomarkers of cardio-metabolic health among the Yakut (Sakha) of northeastern Siberia.

OBJECTIVES: This study provides the first investigation of non-shivering thermogenesis (NST) and brown adipose tissue (BAT) activity among an indigenous circumpolar population, the Yakut of northeastern Siberia. The study also examines the health significance of BAT activity in this population by testing the relationships between BAT thermogenesis and biomarkers of cardio-metabolic disease risk, such as percent body fat and blood glucose and cholesterol levels. METHODS: Data were collected in the Sakha Republic (Yakutia) for 31 men and 43 women. Change in energy expenditure and BAT thermogenesis were quantified after a 30-minute mild cooling condition. Anthropometric dimensions, blood glucose, and lipid levels were also collected. RESULTS: On average, the skin temperature of the supraclavicular area was constant after cooling while the skin temperature of a point on the sternum dropped significantly (P < .001), thus suggesting the presence of active supraclavicular BAT among Yakut adults. Participants with evidence of greater BAT thermogenesis exhibited a larger percent change in energy expenditure (% ΔEE) and an increase in respiratory quotient (RQ) after cooling (P ≤ .05). While there was no relationship between BAT activity and blood lipid levels, BAT thermogenesis was positively associated with blood glucose levels (P < .01). CONCLUSIONS: Yakut adults exhibit evidence of active BAT deposits. Given that there is a significant relationship between BAT activity and % ΔEE, it is possible that BAT plays a role in NST among Yakut adults. While the relationship between BAT and body composition is inconclusive, participants with greater BAT seemed to preferentially utilize glucose during cold stress exposure.

Lifestyle mediates seasonal changes in metabolic health among the yakut (sakha) of northeastern siberia.

OBJECTIVES: Among indigenous circumpolar populations, extreme seasonality influences food availability and energy metabolism. Furthermore, subsistence patterns and wage labor opportunities shift with season. Thus, health measures among circumpolar populations likely exhibit seasonal changes that are influenced by lifestyle factors. This study examines how markers of cardio-metabolic health vary between summer and winter as a function of an individual's lifestyle and sex among the Yakut of northeastern Siberia. METHODS: Anthropometric dimensions, serum lipids and glucose levels, blood pressure, and lifestyle data were collected for a sample of 115 Yakut participants (71 women, 44 men) in Berdygestiakh, Sakha Republic, Russia in the summer of 2009 and winter of 2011. RESULTS: Men and women experienced significant increases in total and HDL cholesterol and triglyceride levels from summer to winter. Women exhibited winter-time increases in adiposity and glucose levels. Men who reported greater market integration were more likely to have lower winter blood pressure levels. Additionally, time spent fishing was associated with lower winter-time LDL cholesterol, while foraging time was associated with higher HDL cholesterol. CONCLUSIONS: While seasonal changes in anthropometric dimensions were modest, Yakut men and women experienced significant increases in total cholesterol and HDL cholesterol from summer to winter. These results also suggest that while Yakut individuals with greater subsistence participation are more buffered from adverse seasonal changes in cholesterol levels, they may be at a greater risk for winter increases in blood pressure. Furthermore, the interactions between lifestyle and seasonal change in metabolic health appear to differ between Yakut women and men. Am. J. Hum. Biol. 28:868-878, 2016. © 2016Wiley Periodicals, Inc.

Granular cell tumor of rectal submucosa: case report / Tumor de células granulares da submucosa rectal: relato de caso

This is a case report of granular cell tumor of rectal submucosa in a female, 35-years-old patient complaining of hematochezia. We describe the histological and immunohistochemical features of the lesion responsible by this clinical find. Following that, we present a discussion of the case based on the literature review, which allowed to proving the infrequency of the tumor in the rectal area and confirms the benign nature of the tumor in this case. (AU)

Este artigo relata o caso de um tumor de células granulares da submocosa retal, em paciente de 35 anos, com queixa de hematoquezia. Fazemos a descrição dos achados histológicos e imuno-histoquímicos da lesão. Além disso, apresenta-se uma discussão do caso com base na revisão da literatura, que permitiu comprovar a infrequência do tumor na região retal e corroborar a benignidade do tumor no presente caso. (AU)

Behavioral attitudes and preferences in cooking practices with traditional open-fire stoves in Peru, Nepal, and Kenya: implications for improved cookstove interventions.

Global efforts are underway to develop and promote improved cookstoves which may reduce the negative health and environmental effects of burning solid fuels on health and the environment. Behavioral studies have considered cookstove user practices, needs and preferences in the design and implementation of cookstove projects; however, these studies have not examined the implications of the traditional stove use and design across multiple resource-poor settings in the implementation and promotion of improved cookstove projects that utilize a single, standardized stove design. We conducted in-depth interviews and direct observations of meal preparation and traditional, open-fire stove use of 137 women aged 20-49 years in Kenya, Peru and Nepal prior in the four-month period preceding installation of an improved cookstove as part of a field intervention trial. Despite general similarities in cooking practices across sites, we identified locally distinct practices and norms regarding traditional stove use and desired stove improvements. Traditional stoves are designed to accommodate specific cooking styles, types of fuel, and available resources for maintenance and renovation. The tailored stoves allow users to cook and repair their stoves easily. Women in each setting expressed their desire for a new stove, but they articulated distinct specific alterations that would meet their needs and preferences. Improved cookstove designs need to consider the diversity of values and needs held by potential users, presenting a significant challenge in identifying a "one size fits all" improved cookstove design. Our data show that a single stove design for use with locally available biomass fuels will not meet the cooking demands and resources available across the three sites. Moreover, locally produced or adapted improved cookstoves may be needed to meet the cooking needs of diverse populations while addressing health and environmental concerns of traditional stoves.

Evidence acquisition and evaluation for evidence summit on population-level behavior change to enhance child survival and development in low- and middle-income countries.

Recognizing the need for evidence to inform public health officials and health care workers in the U.S. government and low- and middle-income country governments on efficient, effective behavior change policies, strategies, and programs for child health and development, the U.S. government convened the Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change. This article summarizes the background and methods for the acquisition and evaluation of the evidence used to the achieve the goals of the summit that is reviewed in other articles in this special issue of the Journal of Health Communication. The process began by identifying focal questions intended to inform the U.S. and low- and middle-income governments about behavior change interventions that accelerate reductions in under-5 mortality and optimize healthy and protective child development to 5 years of age. Experts were selected representing the research and program communities, academia, relevant nongovernmental organizations, and government agencies and assembled into evidence review teams. This was followed by the systematic gathering of relevant peer-reviewed literature that would inform the focal questions. Members of the evidence review teams were invited to add relevant articles not identified in the initial literature review to complete the bibliographies. Details of the search processes and methods used for screening and quality reviews are described. The evidence review teams were asked to comply with a specific evaluation framework for recommendations on practice and policy on the basis of both expert opinion and the quality of the data reviewed.

Seasonal and socioeconomic influences on thyroid function among the Yakut (Sakha) of Eastern Siberia.

OBJECTIVES: Previous research has shown that the extreme cold and short day lengths of polar winters promote increased production and uptake of thyroid hormones, resulting in marked declines in free triiodothyronine (fT3). However, this "polar T3 syndrome" has been documented almost exclusively on small samples of male sojourners and little is known about seasonal changes in thyroid function among indigenous circumpolar groups. The present study addresses this gap by examining seasonal changes in thyroid hormone levels among the indigenous Yakut (Sakha) of northeastern Siberia. METHODS: Anthropometric dimensions and thyroid measures (fT3, free thyroxine [fT4], thyroid-stimulating hormone [TSH]) were obtained on two occasions (July/August, 2009 and January 2011) on a sample of 134 Yakut adults (51 men, 83 women) from the village of Berdygestiakh, Sakha Republic/Yakutia, Russia. RESULTS: Yakut men and women both displayed significant declines in fT3 and fT4, and significant increases in TSH from summer to winter despite showing only modest seasonal changes in body mass and composition. Among men, gains in fat-free mass (FFM) were associated with larger reductions in fT3 and greater increases in TSH. Men living more traditional lifeways showed larger winter declines in fT4 and greater increases in TSH. CONCLUSIONS: The Yakut exhibited significant winter declines in fT3 levels similar to other circumpolar groups studied. However, the magnitude of seasonal change was greater in the Yakut, perhaps reflecting their distinctive metabolic physiology. Lifestyle factors play a mediating role in thyroid responses, such that men with more traditional lifeways had more exaggerated seasonal changes.

Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated. METHODS: A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n=299) was conducted. Those patients who underwent an echocardiogram were identified (n=120) and were assigned to the NCM (n=49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia. RESULTS: 16% of aSAH patients developed NCM. Mortality was higher (p<.001) in the NCM group (n=23[46.9%]) than in the non-CM group (n=28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p=.002) and 12 months (p=.014). The Hunt-Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p=.002) as well as at 1 year (p=.014). NCM was associated with both death (p=.047 CI, 1.012-7.288) and vasospasm (p=.008 CI, 1.34-6.66) after correction for Hunt-Hess grade. Tobacco use (p<.001) and a history of diabetes mellitus (p<.009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p=.047) in multivariate analysis. CONCLUSION: NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality.

Neonatal testosterone exposure protects adult male rats from stroke.

BACKGROUND: Men have a higher stroke incidence compared to women until advanced age. The contribution of hormones to these sex differences has been extensively debated. In experimental stroke, estradiol is neuroprotective, whereas androgens are detrimental. However, prior studies have only examined the effects of acute treatment paradigms; therefore, the timing and mechanism by which ischemic sexual dimorphism arises are unknown. METHODS: The effects of exogenous neonatal androgen exposure on subsequent injury induced by middle cerebral artery occlusion in adulthood in male rats were examined. Rats were administered vehicle (oil), testosterone propionate (TP) or the non-aromatizable androgen dihydrotestosterone (DHT) for 5 days after birth. At 3 months of age, a focal stroke was induced. RESULTS: Testosterone-treated rats (but not DHT-treated animals) had decreased infarct volumes (20 vs. 33%, p < 0.05) as well as increased estradiol levels (39.4 vs. 18.6 pg/ml, p < 0.0001) compared to oil-treated animals. TP-injected males had increased testicular aromatase (P450arom) levels (3.6 vs. 0.2 ng/ml, p < 0.0001) compared to oil-treated males. The level of X-linked inhibitor of apoptosis, the primary endogenous inhibitor of caspase-induced apoptosis, was increased in TP-treated rats compared with the oil-treated males. CONCLUSIONS: Neonatal exposure to exogenous testosterone upregulates testicular aromatase expression in male rats and leads to adult neuroprotection secondary to changes in serum estradiol levels and cell death proteins. This study suggests that early exposure to gonadal hormones can have dramatic effects on the response to adult cerebrovascular injury.