Elucidating the mechanisms responsible for driving individual variation in behavior is a foundational question in organismal biology. Answering these types of questions is necessary for understanding how tradeoffs are mediated as well as potential constraints on evolutionary responses to selection. In Chapter I, I synthesize the evidence suggesting that testosterone plays a central role in driving individual variation in cooperative reproductive behaviors and mediating the tradeoff between cooperation and competition. The subsequent chapters of my dissertation then focus on understanding the mechanistic sources of individual variation in the cooperative courtship behaviors of male wire-tailed manakins (Pipra filicauda), a Neotropical lekking songbird. Wire-tailed manakins exhibit cooperative courtship display behaviors wherein both floater and territory-holding males perform coordinated courtship displays. Territory-holding males sire essentially all offspring and, among territory-holders, those that are more cooperative exhibit higher reproductive success. Cooperation also benefits floater males in that more cooperative floater males have a higher probability of becoming a territory-holder. In Chapter II, I detail the difficulties associated with measuring circulating testosterone in free-living animals and develop a new field technique that can improve our ability to accurately account for the effects that the stress of capture has on circulating testosterone levels in birds. In Chapter III, I quantify individual variation in the cooperative courtship behaviors of territory-holding male wire-tailed manakins using video cameras. I then use both observational and experimental approaches to show that among territory holders, high testosterone has antagonistic effects on a male's cooperative behavior. Chapter IV focuses on quantifying how an individual's cooperative behavior relates to their telomere length. Telomeres are the segments of repetitive DNA found at the end of chromosomes. Telomeres shorten in response to both physiological and environmental perturbations, are predictive of an individual's mortality risk and, because of these characteristics, are thought to reflect an individual's biological age (as opposed to chronological age). My results show that short telomeres are associated with increased cooperative behaviors and, given that a male's cooperative behavior is reflective of their reproductive investment, suggest that males with lower future reproductive potential (i.e., shorter telomeres) invest more in reproduction. My last chapter (Chapter V) focuses on synthesizing these results and suggests that future research on cooperative behaviors will need to integrate biomarkers of an individual's condition with mechanisms that reflect an individual's social competence to further understand the sources of individual variation in cooperation. / Doctor of Philosophy / Cooperative reproductive behaviors occur when multiple individuals coordinate their reproductive efforts to gain an advantage over other individuals or those individuals that attempt to reproduce in the absence of cooperation. In this context, some individuals have been found to consistently act more or less cooperative, and outstanding questions regarding the evolution of cooperative reproductive behaviors focus on attempting to understand the intrinsic differences among individuals that consistently vary in their cooperative tendencies. In this dissertation, I focus on measuring individual variation in the cooperative reproductive behavior of male wire-tailed manakins, a passerine found in the Amazon Rainforest, as well as the sources of this individual variation. Male wire-tailed manakins perform acrobatic courtship displays for females. Wire-tailed manakins are especially interesting in that multiple males will perform coordinated courtship displays, but only one male within the group typically reproduces. Individual variation in this cooperative behavior also influences how likely an individual is to reproduce. Chapter I synthesizes the evidence across species to suggest that testosterone, a hormone known for influencing competitive reproductive behaviors, influences an individual’s likelihood of acting in a cooperative or competitive manner. Chapter II describes the difficulties associated with measuring circulating testosterone in wild animals and describes techniques that can be used to overcome some of the difficulties associated with measuring circulating testosterone in free-living birds. Chapter III focuses on understanding the relationship between testosterone and individual differences in the cooperative reproductive behaviors of the wire-tailed manakin. I find that those males with higher testosterone or those with experimentally increased testosterone are less cooperative. I discuss my results in the context of understanding how this relationship could influence the evolution of circulating testosterone levels more broadly. Chapter IV examines the relationship between the cooperative reproductive behavior of male wire-tailed manakins and the repetitive segments of DNA found at the end of chromosomes called telomeres. Telomeres shorten as individuals age and the length of an individual’s telomeres has been found to be predictive of their lifespan and mortality risk. My research shows that those individuals with shorter telomeres (or a higher mortality risk) are more cooperative. Given that an individual’s cooperative behavior is predictive of their probability of successfully reproducing, my research suggests that those individuals that are more likely to perish invest more time and energy in attempting to reproduce. In Chapter V, I conclude by summarizing my results and suggesting future research that can further our understanding of the sources of consistent individual differences in cooperative behavior and the evolution of cooperation more broadly.

No / Peripheral intracrine sex steroid synthesis from adrenal precursors dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought to establish if there are differences in intracrine, paracrine, and endocrine regulation of sex steroids by primary cultures of human skin epidermal keratinocytes and dermal fibroblasts. Microarray analysis identified multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA expression, enzymatic assay aromatase activity, scratch assay cell migration, immunocytochemistry α-smooth muscle actin (α-SMA), and collagen gel fibroblast contraction. All steroidogenic components were present, although only keratinocytes expressed the organic anion organic anion transporter protein (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor (GPER1). Steroids modulated multifunctional genes, up-regulating genes important in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif) ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)]. DHEA-sulfate (DHEA-S), DHEA, and 17β-estradiol stimulated keratinocyte and fibroblast migration at early (4 h) and late (24–48 h) time points, suggesting involvement of genomic and nongenomic signaling. Migration was blocked by aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis to estrogen. Testosterone had little effect, implying it is not an intermediate. Steroids stimulated fibroblast contraction but not α-SMA expression. Mechanical wounding reduced fibroblast aromatase activity but increased keratinocyte activity, amplifying the bioavailability of intracellular estrogen. Cultured fibroblasts and keratinocytes provide a biologically relevant model system to investigate the complex pathways of sex steroid intracrinology in human skin.—Pomari, E., Valle, L. D., Pertile, P., Colombo, L., and Thornton, M. J. Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts.

Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Although testosterone therapy consistently increases hematocrit levels across numerous clinical trials, the factors that affect the relationship between testosterone therapy and on-treatment hematocrit are poorly understood. Here, the effect of testosterone on hematocrit levels was contrasted across subgroups of men from 2 randomized, placebo-controlled trials involving testosterone gel therapy: the Testosterone and Erectile Dysfunction (TED; ClinicalTrials.gov # NCT00512707; n = 130) and the Testosterone in Older Men (TOM; ClinicalTrials.gov # NCT00240981; n = 152). Hematocrit elevations with testosterone therapy were greater among men self-identifying as white (difference between white and black men 2.32, 95% CI 1.03, 3.61; P = 0.0005). Compliance to therapy also modified the effect of testosterone on hematocrit (difference between participants with 99 to 100% vs. 21 to 87% compliance with therapy 1.83%; 95% CI 0.23, 3.42; P = 0.026). On-treatment hematocrit levels were greater among older men (difference between 75 to 87 and 50 to 57 years 1.66%; 95% CI 0.08, 3.24; P = 0.039) and men with hypertension (difference between men with and without hypertension 1.31; 95% CI 0.14, 2.48; P = 0.028). On-treatment hematocrit levels were smaller among men who smoke(treatment effect difference between smokers and non-smokers -1.22%; 95% CI -2.80, 0.36; P = 0.129), men with Chronic Obstructive Pulmonary Disorder (difference - 2.92%; 95% CI -6.41, 0.58; P = 0.101), and those with sleep apnea (difference - 0.88; 95% CI -2.93, 1.16; P = 0.40), however the numbers of men reporting these characteristics are too small to draw strong conclusions. In conclusion, greater increases in hematocrit levels with testosterone therapy may associate with greater compliance, having hypertension, advanced age, and white race. / 2999-01-01

Hypoactive sexual desire or low libido in women are collectively referred to as hypoactive sexual desire disorder (HSDD). HSDD is estimated to occur in 10% to 15% of adult women. HSDD is likely the most common female sexual dysfunction (FSD) in menopausal women. The hallmark of the diagnosis is personal distress and interpersonal difficulties resulting from low sex drive. Most women will not seek help for this problem. Studies have suggested that primary care providers and gynecologic healthcare providers report not feeling qualified to treat patients with sexual dysfunction, especially HSDD. Testosterone, specifically transdermal testosterone, has been suggested to play an integral part in the treatment of HSDD in menopause. It is proven to increase the frequency of satisfying sexual activity, sexual desire, and orgasmic response, and to decrease personal distress. Testosterone has a demonstrated a safety history and medication tolerance when prescribed for this purpose. In spite of its proven efficacy in relation to HSDD, the Food and Drug Administration (FDA) has not approved testosterone for this purpose, though its use for HSDD is currently suggested by the Endocrine Society in their Clinical Practice Guidelines (CPGs). The primary purpose of this study was to assess Vermont primary care providers' and gynecologic healthcare providers' perceptions, knowledge, and practices regarding treatment of HSDD in naturally induced menopause with a focus on transdermal testosterone. After respondent inclusion criteria and demographic information about the respondents was collected, the study asked questions and tested knowledge about topics regarding menopause and sexuality, evaluation of FSD, and treatment of low libido and diminished sexual desire with a focus on testosterone. The study was a descriptive cross-sectional online survey that was completed electronically on a secure server through the University of Vermont. The conclusions were that providers believe sexuality and sexual satisfaction are quality of life indicators and perceived that maintaining sexual function is important to naturally occurring menopausal women. The majority of providers would prescribe a pharmaceutical treatment for menopausal women seeking to maintain their sexual function, enhance sexual satisfaction, and/or treat symptoms of HSDD as long as there were no contraindications. However, testosterone, a proven treatment for women with complaints of low libido and/or diminished sexual desire, was reportedly underutilized. This may be related to inconsistent screening for FSD in menopause at each comprehensive visit and lack of provider knowledge about testosterone (including safety and efficacy) impacting confidence to prescribe testosterone for this purpose. Further, providers were divided on whether low libido and/or diminished sexual desire in naturally occurring menopause is a medical condition or disorder or a natural part of aging. It is unclear how the aforementioned divisions impact evaluation and treatment.

Decreased testosterone levels (hypogonadism) in middle-aged men (aged 45-64) has been associated with increased levels of depression. Studies have suggested that increases in anxiety and/or attention problems may also be associated with hypogonadism but have not provided empirical evidence to support these suggestions. The purpose of this quantitative study was to examine depression, anxiety, and attention problems in middle-aged men using a psychological self-report inventory. The theoretical model used in this study was the biomedical model, which combined pharmacological treatment with psychological self-report inventories to determine if there was an association or relationship between the testosterone levels in men and the psychological distress experienced by men who have become hypogonadal. A total of 179 males were recruited through local physicians. There was a statistically significant difference and a small size effect in the level of depression, anxiety, and/or attention issues experienced by those who were receiving TRT versus those who were not. This study may provide some guidance to medical clinicians, such as psychiatrists, primary-care physicians, and endocrinologists, as well as clinical psychologists who see middle-aged men in their practice settings.

<p>Anabolic androgenic steroids are testosterone and its derivates. Testosterone is the most important naturally existing sex hormone for men and is used for its anabolic effects providing increased muscle mass. Testosterone is taken orally or by intramuscular injection in its ester form and are available illegally in different forms of esters. Anabolic androgenic steroids are today analyzed only in urine. To differentiate between the human natural testosterone and exogenous supply the quote natural testosterone and epitestosterone is used. Detection of testosterone esters in serum is an unmistakable proof of exogenous supply of testosterone. The aim of this thesis was to find a method for determining testosterone esters in serum and to study an extraction method possible for quantification of testosterone esters in serum.</p><p>The technique used to separate and identify the Testosterone esters was Liquid Chromatography Tandem Mass Spectrometry Electro Spray Ionisation. Parameters for chromatography and mass detection were optimized for nine testosterone esters and evaluated according to selectivity, resolution and intensity. A method that could be used for determination of testosterone esters in serum was found. The MS-method was set and at least three possible transitions for each testosterone ester were found. The best choice of column proved to be the C18 column where all the esters were separated and seven of them were base-line separated. The C18 column along with methanol and ammonium acetate buffer, 5 mM, pH 5 showed the highest sensitivity for Multiple Reaction Monitoring-detection. A gradient profile for a total runtime of 5.6 minutes was established. Two alternative extraction procedures were tested, with <em>tert</em>-butylmethylether or diethyl ether/ethyl acetate and both seemed to work satisfactory. Analysis of serum proved to work well and no severe interference occurred. Results from the linearity tests indicate that future quantification method in serum will be possible.</p>

Anabolic androgenic steroids are testosterone and its derivates. Testosterone is the most important naturally existing sex hormone for men and is used for its anabolic effects providing increased muscle mass. Testosterone is taken orally or by intramuscular injection in its ester form and are available illegally in different forms of esters. Anabolic androgenic steroids are today analyzed only in urine. To differentiate between the human natural testosterone and exogenous supply the quote natural testosterone and epitestosterone is used. Detection of testosterone esters in serum is an unmistakable proof of exogenous supply of testosterone. The aim of this thesis was to find a method for determining testosterone esters in serum and to study an extraction method possible for quantification of testosterone esters in serum. The technique used to separate and identify the Testosterone esters was Liquid Chromatography Tandem Mass Spectrometry Electro Spray Ionisation. Parameters for chromatography and mass detection were optimized for nine testosterone esters and evaluated according to selectivity, resolution and intensity. A method that could be used for determination of testosterone esters in serum was found. The MS-method was set and at least three possible transitions for each testosterone ester were found. The best choice of column proved to be the C18 column where all the esters were separated and seven of them were base-line separated. The C18 column along with methanol and ammonium acetate buffer, 5 mM, pH 5 showed the highest sensitivity for Multiple Reaction Monitoring-detection. A gradient profile for a total runtime of 5.6 minutes was established. Two alternative extraction procedures were tested, with tert-butylmethylether or diethyl ether/ethyl acetate and both seemed to work satisfactory. Analysis of serum proved to work well and no severe interference occurred. Results from the linearity tests indicate that future quantification method in serum will be possible.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (doctoral)--Universiteit Utrecht, 1995. / Summaries in English and French.

Thesis (M.A.)--University of Alabama at Birmingham, 2007. / Description based on contents viewed Oct. 5, 2007; title from title screen. Includes bibliographical references (p. 31-34).