Browsing by Subject "Testosterone"
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Item Open Access Defects of prostate development and reproductive system in the estrogen receptor-alpha null male mice.(Endocrinology, 2009-01) Chen, Ming; Hsu, Iawen; Wolfe, Andrew; Radovick, Sally; Huang, KuoHsiang; Yu, Shengqiang; Chang, Chawnshang; Messing, Edward M; Yeh, ShuyuanThe estrogen receptor-alpha knockout (ERalphaKO, ERalpha-/-) mice were generated via the Cre-loxP system by mating floxed ERalpha mice with beta-actin (ACTB)-Cre mice. The impact of ERalpha gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERalpha(-/-) male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERalpha(-/-) male mice are 2-fold elevated. The ACTB-Cre/ERalpha(-/-) testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERalpha(-/-) mice display reduced branching morphogenesis. Loss of ERalpha could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERalpha(-/-) prostates. Collectively, these results suggest that ERalpha is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment.Item Open Access Developmental nicotine exposure and masculinization of the rat preoptic area.(Neurotoxicology, 2022-03) Joglekar, Rashmi; Cauley, Marty; Lipsich, Taylor; Corcoran, David L; Patisaul, Heather B; Levin, Edward D; Meyer, Joel N; McCarthy, Margaret M; Murphy, Susan KNicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.Item Open Access Dominance, politics, and physiology: voters' testosterone changes on the night of the 2008 United States presidential election.(PLoS One, 2009-10-21) Stanton, SJ; Beehner, JC; Saini, EK; Kuhn, CM; LaBar, KSBACKGROUND: Political elections are dominance competitions. When men win a dominance competition, their testosterone levels rise or remain stable to resist a circadian decline; and when they lose, their testosterone levels fall. However, it is unknown whether this pattern of testosterone change extends beyond interpersonal competitions to the vicarious experience of winning or losing in the context of political elections. Women's testosterone responses to dominance competition outcomes are understudied, and to date, a clear pattern of testosterone changes in response to winning and losing dominance competitions has not emerged. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated voters' testosterone responses to the outcome of the 2008 United States Presidential election. 183 participants provided multiple saliva samples before and after the winner was announced on Election Night. The results show that male Barack Obama voters (winners) had stable post-outcome testosterone levels, whereas testosterone levels dropped in male John McCain and Robert Barr voters (losers). There were no significant effects in female voters. CONCLUSIONS/SIGNIFICANCE: The findings indicate that male voters exhibit biological responses to the realignment of a country's dominance hierarchy as if they participated in an interpersonal dominance contest.Item Open Access Evaluating testosterone as a phenotypic integrator: From tissues to individuals to species.(Molecular and cellular endocrinology, 2019-10) Lipshutz, SE; George, EM; Bentz, AB; Rosvall, KAHormones have the potential to bring about rapid phenotypic change; however, they are highly conserved over millions of years of evolution. Here, we examine the evolution of hormone-mediated phenotypes, and the extent to which regulation is achieved via independence or integration of the many components of endocrine systems. We focus on the sex steroid testosterone (T), its cognate receptor (androgen receptor) and related endocrine components. We pose predictions about the mechanisms underlying phenotypic integration, including coordinated sensitivity to T within and among tissues and along the HPG axis. We then assess these predictions with case studies from wild birds, asking whether gene expression related to androgenic signaling naturally co-varies among individuals in ways that would promote phenotypic integration. Finally, we review how mechanisms of integration and independence vary over developmental or evolutionary time, and we find limited support for integration.Item Open Access Field-Based Assessments of Behavioral Patterns During Shiftwork in Police Academy Trainees Using Wearable Technology.(Journal of biological rhythms, 2022-06) Erickson, Melissa L; Wang, Will; Counts, Julie; Redman, Leanne M; Parker, Daniel; Huebner, Janet L; Dunn, Jessilyn; Kraus, William ECircadian misalignment, as occurs in shiftwork, is associated with numerous negative health outcomes. Here, we sought to improve data labeling accuracy from wearable technology using a novel data pre-processing algorithm in 27 police trainees during shiftwork. Secondarily, we explored changes in four metabolic salivary biomarkers of circadian rhythm during shiftwork. Using a two-group observational study design, participants completed in-class training during dayshift for 6 weeks followed by either dayshift or nightshift field-training for 6 weeks. Using our novel algorithm, we imputed labels of circadian misaligned sleep episodes that occurred during daytime, which were previously were mislabeled as non-sleep by Garmin, supported by algorithm performance analysis. We next assessed changes to resting heart rate and sleep regularity index during dayshift versus nightshift field-training. We also examined changes in field-based assessments of salivary cortisol, uric acid, testosterone, and melatonin during dayshift versus nightshift. Compared to dayshift, nightshift workers experienced larger changes to resting heart rate, sleep regularity index (indicating reduced sleep regularity), and alterations in sleep/wake activity patterns accompanied by blunted salivary cortisol. Salivary uric acid and testosterone did not change. These findings show wearable technology combined with specialized data pre-processing can be used to monitor changes in behavioral patterns during shiftwork.Item Open Access Hormone naïve prostate cancer: predicting and maximizing response intervals.(Asian journal of andrology, 2015-11) Moul, Judd WHormone naïve advanced prostate cancer is subdivided into two disease states: biochemical recurrence and traditional M1 (metastatic) prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy (ADT). In biochemical recurrence/prostate-specific antigen (PSA) recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade (peripheral androgen deprivation) to complete hormonal therapy (combined androgen blockade [CAB]) remains in debate owing to lack of randomized controlled trials (RCT). However, there is good RCT support for use of intermittent hormonal therapy (IHT). There is also limited research on biomarker response (PSA and testosterone decline) to predict prognosis. On the other hand, in the setting of M1 hormone naïve prostate cancer, there are many more RCT's to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone (T) control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M1 patient, maintaining a serum T below 20-30 ng dl-1 prolongs the response to ADT. Novel oral agents (abiraterone and enzalutamide) may soon find use in hormone naïve disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.Item Open Access Nesting strategy shapes territorial aggression but not testosterone: A comparative approach in female and male birds.(Hormones and behavior, 2021-07) Lipshutz, Sara E; Rosvall, Kimberly AOur understanding of the proximate and ultimate mechanisms shaping competitive reproductive phenotypes primarily stems from research on male-male competition for mates, even though competition is widespread in both sexes. We evaluate the hypothesis that the restricted nature of a resource required for reproduction, i.e. nest site, is a key variable driving territorial competition and testosterone secretion in female and male birds. Obligate secondary cavity-nesting has evolved repeatedly across avian lineages, providing a useful comparative context to explore how competition over limited nest cavities shapes aggression and its underlying mechanisms across species. Although evidence from one or another cavity-nesting species suggests that territorial aggression is adaptive in both females and males, this has not yet been tested in a comparative framework. We predicted that cavity-nesting generates more robust territorial aggression, in comparison to close relatives with less restrictive nesting strategies. Our focal species were two obligate secondary cavity-nesting species and two related species with more flexible nesting strategies in the same avian family: tree swallow (Tachycineta bicolor) vs. barn swallow (Hirundo rustica); Eastern bluebird (Sialia sialis) vs. American robin (Turdus migratorius). We assayed conspecific aggression using simulated territorial intrusion and found that cavity-nesting species displayed greater territorial aggression than their close relatives. This pattern held for both females and males. Because territorial aggression is often associated with elevated testosterone, we also hypothesized that cavity-nesting species would exhibit higher testosterone levels in circulation. However, cavity-nesting species did not have higher testosterone in circulation for either sex, despite some correlative evidence that testosterone is associated with higher rates of physical attack in female tree swallows. Our focus on a context that is relevant to both sexes - competition over essential breeding resources - provides a useful framework for co-consideration of proximate and ultimate drivers of reproductive competition in females and males.Item Open Access Organizational and activational androgens, lemur social play, and the ontogeny of female dominance.(Hormones and behavior, 2019-07-02) Grebe, Nicholas M; Fitzpatrick, Courtney; Sharrock, Katherine; Starling, Anne; Drea, Christine MThe role of androgens in shaping "masculine" traits in males is a core focus in behavioral endocrinology, but relatively little is known about an androgenic role in female aggression and social dominance. In mammalian models of female dominance, including the ring-tailed lemur (Lemur catta), links to androgens in adulthood are variable. We studied the development of ring-tailed lemurs to address the behavioral basis and ontogenetic mechanisms of female dominance. We measured behavior and serum androgen concentrations in 24 lemurs (8 males, 16 females) from infancy to early adulthood, and assessed their 'prenatal' androgen milieu using serum samples obtained from their mothers during gestation. Because logistical constraints limited the frequency of infant blood sampling, we accounted for asynchrony between behavioral and postnatal hormone measurements via imputation procedures. Imputation was unnecessary for prenatal hormone measurements. The typical sex difference in androgen concentrations in young lemurs was consistent with adult conspecifics and most other mammals; however, we found no significant sex differences in rough-and-tumble play. Female (but not male) aggression increased beginning at approximately 15 months, coincident with female puberty. In our analyses relating sexually differentiated behavior to androgens, we found no relationship with activational hormones, but several significant relationships with organizational hormones. Notably, associations of prenatal androstenedione and testosterone with behavior were differentiated, both by offspring sex and by type of behavior within offspring sexes. We discuss the importance of considering (1) missing data in behavioral endocrinology research, and (2) organizational androgens other than testosterone in studies of female dominance.Item Open Access Personalized nutrition therapy in critical care: 10 expert recommendations.(Critical care (London, England), 2023-07) Wischmeyer, Paul E; Bear, Danielle E; Berger, Mette M; De Waele, Elisabeth; Gunst, Jan; McClave, Stephen A; Prado, Carla M; Puthucheary, Zudin; Ridley, Emma J; Van den Berghe, Greet; van Zanten, Arthur RHPersonalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.Item Open Access Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor α knockout mice.(Asian journal of andrology, 2012-07) Chen, Ming; Yeh, Chiuan-Ren; Shyr, Chih-Rong; Lin, Hsiu-Hsia; Da, Jun; Yeh, ShuyuanEarly studies suggested that estrogen receptor alpha (ERα) is involved in estrogen-mediated imprinting effects in prostate development. We recently reported a more complete ERα knockout (KO) mouse model via mating β-actin Cre transgenic mice with floxed ERα mice. These ACTB-ERαKO male mice showed defects in prostatic branching morphogenesis, which demonstrates that ERα is necessary to maintain proliferative events in the prostate. However, within which prostate cell type ERα exerts those important functions remains to be elucidated. To address this, we have bred floxed ERα mice with either fibroblast-specific protein (FSP)-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERα gene in either stromal fibroblast (FSP-ERαKO) or epithelial (pes-ERαKO) prostate cells. We found that circulating testosterone and fertility were not altered in FSP-ERαKO and pes-ERαKO male mice. Prostates of FSP-ERαKO mice have less branching morphogenesis compared to that of wild-type littermates. Further analyses indicated that loss of stromal ERα leads to increased stromal apoptosis, reduced expression of insulin-like growth factor-1 (IGF-1) and FGF10, and increased expression of BMP4. Collectively, we have established the first in vivo prostate stromal and epithelial selective ERαKO mouse models and the results from these mice indicated that stromal fibroblast ERα plays important roles in prostatic branching morphogenesis via a paracrine fashion. Selective deletion of the ERα gene in mouse prostate epithelial cells by probasin-Cre does not affect the regular prostate development and homeostasis.Item Open Access Testosterone secretion varies in a sex- and stage-specific manner: Insights on the regulation of competitive traits from a sex-role reversed species.(General and comparative endocrinology, 2020-06) Lipshutz, Sara E; Rosvall, Kimberly ATestosterone (T) mediates a variety of traits that function in competition for mates, including territorial aggression, ornaments, armaments, and gametogenesis. The link between T and mating competition has been studied mainly in males, but females also face selection pressures to compete for mates. Sex-role reversed species, in which females are the more competitive sex, provide a unique perspective on the role of T in promoting competitive traits. Here, we examine patterns of T secretion in sex-role reversed northern jacanas (Jacana spinosa) during breeding, when females are fertile and males are either seeking copulations or conducting parental care. We measured baseline levels of T in circulation along with a suite of behavioral and morphological traits putatively involved in mating competition. We evaluated hypotheses that levels of T track gonadal sex and parental role, and we begin to investigate whether T and competitive traits co-vary in a sex- and stage- specific manner. Although females had higher expression of competitive traits than males at either breeding stage, we found that females and incubating males had similar levels of T secretion, which were lower than those observed in copulating males. T was correlated with wing spur length in females and testes mass in copulating males, but was otherwise uncorrelated with other competitive traits. These findings suggest that levels of T in circulation alone do not predict variation in competitive traits across levels of analysis, including gonadal sex and parental role. Instead, our findings coupled with prior research indicate that selection for female mating competition and male care may generate different physiological regulation of competitive traits.