Circulating Sex Steroid Concentrations Research Articles

Abstract 141: Associations Between Sex Steroids And Cardiac Arrest Outcomes

Introduction: Sudden cardiac arrest (SCA) is one of the leading causes of death in both males and females although females tend to have better outcomes. While sex steroids influence cardiovascular disease, and low level of testosterone and high level of estradiol is associated with the risk of SCA, little is known about their changes after a cardiac arrest, and their association to outcomes. We sought to characterize the temporal trajectories in sex steroids (estrogens [estrone and estradiol], progesterone, and testosterone) in the post-return of spontaneous circulation (ROSC) phase and determine associations with survival and neurological outcomes. Hypothesis: Sex steroids and their temporal trajectories post-SCA are associated with survival and neurological outcomes. Methods: Plasma samples from SCA patients (n=65, 74% males) were collected at the University of Texas Houston between May 2018-March 2020 at four serial time points (0, 6, 24, 48h) post-ROSC. Quantitative sex hormone analysis was performed using LCMS. Data was analyzed by t-test, Chi 2 test and Generalized Estimating Equation (GEE) with p<0.05 indicating significance. Results: There were no differences in demographic and clinical characteristics between males and females. Plasma estrogens peaked at 24 hours, whereas progesterone and testosterone peaked at 6 hours. Estrogens and testosterone were higher in males, while progesterone trended higher in females. Hormonal trajectories did not differ by survival, however, testosterone concentrations were lower in patients with good neurological recovery. Lower estradiol was associated with survival (β: -13.80, p=0.016) adjusting for sex, time, and age, while a lower testosterone was associated with good neurological recovery (β: -0.68, p=0.031) adjusting for time. Conclusion: Increased circulating sex steroid concentrations were observed in the post-ROSC phase after SCA. High levels of estrogens were associated with worse survival independent of sex, and lower testosterone levels were associated with better neurological recovery. A larger sample size and simultaneous measurement of cortisol will be important to better understand the role of sex hormones in outcomes after SCA.

Bone health in ageing men.

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men.

Gene expression of sex steroid metabolizing enzymes and receptors in the skeletal muscle of migrant and resident subspecies of white-crowned sparrow (Zonotrichia leucophrys).

Circulating sex steroid concentrations vary dramatically across the year in seasonally breeding animals. The ability of circulating sex steroids to effect muscle function can be modulated by changes in intracellular expression of steroid metabolizing enzymes (e.g., 5α-reductase type 2 and aromatase) and receptors. Together, these combined changes in plasma hormones, metabolizing enzymes and receptors allow for seasonally appropriate changes in skeletal muscle function. We tested the hypothesis that gene expression of sex steroid metabolizing enzymes and receptors would vary seasonally in skeletal muscle and these changes would differ between a migrant and resident life history strategy. We quantified annual changes in plasma testosterone and gene expression in pectoralis and gastrocnemius skeletal muscles using quantitative polymerase chain reaction (qPCR) in free-living migrant (Zonotrichia leucophrys gambelii) and resident (Z. l. nuttalli) subspecies of white-crowned sparrow during breeding, pre-basic molt, and wintering life history stages. Pectoralis muscle profile was largest in migrants during breeding, while residents maintained large muscle profiles year-round. Circulating testosterone peaked during breeding in both subspecies. Pectoralis muscle androgen receptor mRNA expression was lower in females of both subspecies during breeding. Estrogen receptor-α expression was higher in the pectoralis muscle, but not gastrocnemius, of residents throughout the annual cycle when compared to migrants. Pectoralis aromatase expression was higher in resident males compared to migrant males. No differences were observed for 5α-reductase 2. Between these two subspecies, patterns of plasma testosterone and androgen receptors appear to be conserved, however estrogen receptor gene expression appears to have diverged.

Consequences of temperature-induced sex reversal on hormones and brain in Nile tilapia (Oreochromis niloticus)

Fish present a wide variety of sex determination systems ranging from strict genetic control (genetic sex determination, GSD) to strict environmental control (environmental sex determination, ESD). Temperature is the most frequent environmental factor influencing sex determination. Nile tilapia (Oreochromis niloticus) is characterized by GSD with male heterogamety (XY/XX), which can be overridden by exposure to high masculinizing temperatures. Sex reversed Nile tilapia (XX males; neomales) have been described in the wild and seem undistinguishable from XY males, but little is known about their physiology. The consideration of climate change urges the need to understand the possible physiological and behavioral consequences of such a sex reversal. The present study compared XX females, XY males and XX neomales for testis maturation, circulating sex -steroid concentrations as well as the size and number of neurons expressing arginine-vasotocin [AVT] and gonadotropin releasing hormone [GnRH] which are involved in sociosexual pathways. The results revealed that temperature-induced sex reversal does not affect testis maturation nor circulating sex steroid concentrations. Neomales show dramatically fewer GnRH1-immunoreactive (-ir) neurons than males and females, despite the observed normal testis physiology. Neomales also present fewer AVT-ir neurons in the magnocellular preoptic area than females and bigger AVT-ir neurons in the parvocellular POA (pPOA) compared to both males and females. The absence of consequences of sex reversal on testis development and secretions despite the reduced numbers of GnRH1 neurons suggests the existence of compensatory mechanisms in the hypothalamic-pituitary-gonadal axis, while the larger pPOA AVT neurons might predict a more submissive behavior in neomales.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

Digit ratio (2D:4D) and circulating testosterone, oestradiol, and progesterone levels across the menstrual cycle

BackgroundDigit ratio (2D:4D) is used by researchers as an indicator of prenatal sex hormone exposure. Two previous studies have examined associations between 2D:4D and circulating sex steroid concentrations across the menstrual cycle in adult females. One reported that digit ratio correlated positively with oestradiol levels, whereas the other found no such effect; neither observed significant associations with progesterone. AimsTo examine associations between 2D:4D, as well as asymmetry (i.e. right minus left 2D:4D), and circulating sex steroids across the menstrual cycle. Study designCorrelational. Subjects32 naturally cycling adult females from rural southern Poland. Outcome measuresSalivary oestradiol, progesterone, testosterone, and testosterone to oestradiol ratio (T:O) measured during the follicular, peri-ovulatory, and luteal phases. Average levels across the cycle were also examined. Results and conclusionsAsymmetry in digit ratio correlated positively with oestradiol at each phase, as well as with average levels across the cycle. Each association, other than that relating to average levels, remained statistically significant after a range of covariates had been controlled for. No other significant correlations were observed between digit ratio variables and circulating hormone levels. Our results might suggest that low exposure to androgens and/or high exposure to oestrogens during gestation is a predictor of high oestradiol levels in naturally cycling females of reproductive age. However, considering that it was asymmetry in digit ratio, and not either right or left 2D:4D, that was a significant predictor, it is also possible that these effects reflect more general associations between bilateral asymmetry and circulating oestradiol levels.

Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.

Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases.Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers.Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone (r2 = 0.10), and then serum estrone and tissue estrone (r2 = 0.09). There was no effect modification by Gleason score, race, or age.Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu.Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(11); 1660-6. ©2017 AACR.

Zusammenhang zwischen Sexualhormonen und schwerer Arthrose bei Männern

Hussain SM et al. Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men.

Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study.

Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 × 10−5; q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

Pre-diabetes and serum sex steroid hormones among US men.

Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68ng/mL) than without (5.36ng/mL, p=0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67nmol/L) than without (36.16nmol/L; p=0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone and SHBG and higher free estradiol levels.

Short-Term Estrogen Withdrawal Increases Adiposity in Healthy Men.

T deprivation increases risk of insulin resistance in men, but whether this risk is independent of changes in body composition is unknown. Further, the metabolic roles of T and its metabolite estradiol have not been clearly defined in men. This study sought to establish the effects of selective sex steroid withdrawal on insulin sensitivity in healthy men. This was a double-blinded, placebo-controlled, randomized trial at an academic medical center of 56 healthy men, 19-55 years of age. Subjects received the GnRH antagonist acyline plus one of the following: placebo gel (Castrate), 1.25 g testosterone gel (Low T/E), 5 g testosterone gel (Normal T/E), or 5 g testosterone gel with letrozole (Normal T/Low E) daily for 4 weeks. Body composition and glucose tolerance were assessed at baseline and end of treatment. Insulin sensitivity was quantified by the Matsuda index. Predicted circulating sex steroid concentrations were achieved in all treatment groups. The time-by-group interaction for Matsuda index did not achieve significance in overall repeated measures ANOVA (baseline vs week 4; P = .16). A significant time-by-group interaction was observed for fat mass (P = .003), with changes in fat mass attributable predominantly to estrogen exposure in linear regression analysis (P = .016). A time-by-group interaction also was observed for lean mass (P = .03) and influenced by androgen exposure (P = .003). Short-term sex steroid withdrawal in healthy men causes adverse changes in body composition. These findings support the role of estradiol as a determinant of adiposity in men.

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men

Few studies have examined the association between circulating sex steroid concentrations and risk of osteoarthritis (OA) in men with inconsistent results. Our aim was to examine whether concentrations of circulating sex steroid hormones were associated with the incidence of primary knee and hip arthroplasty for OA in a prospective cohort study. Two thousand four hundred and ninety four men from the Melbourne Collaborative Cohort Study (MCCS) had circulating sex steroid concentrations measured in blood samples drawn at recruitment (1990-1994) and stored in liquid nitrogen. The plasma concentrations of sex hormones, including dehydroepiandrosterone sulphate, androstenedione, testosterone, estradiol, androstanediol glucuronide, and sex hormone binding globulin, were measured. The incidence of total knee and hip arthroplasty for OA during 2001-2013 was determined by linking MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. One hundred and four men had knee and 80 had hip arthroplasty for OA over 10.7 (SD 3.8) years. Higher concentrations of androstenedione were associated with a decreased risk of total knee (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.77-0.98) and hip (HR 0.84 95% CI 0.71-1.00) arthroplasty for OA in overweight and obese men. No significant association was observed for the other measured hormones. Low plasma androstenedione concentration is associated with an increased risk of both knee and hip arthroplasty for OA for overweight and obese men. While the findings need to be confirmed in other cohort studies, they suggest that circulating sex steroids may play a role in the pathogenesis of OA in men.

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men

Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men

Responses of sex steroid hormones to different intensities of exercise in endurance athletes.

Previous studies have shown that acute exercise elevates sex steroid hormone concentrations in rodents and that sprint exercise increases circulating testosterone in healthy young men. However, the effect of different exercise intensities on sex steroid hormone responses at different levels of physical fitness is still unclear. In this study, we compared circulating sex steroid hormone responses at different exercise intensities in athletes and non-athletes. Eight male endurance athletes and 11 non-athletes performed two 15 min sessions of submaximal exercise at 40 and 70% peak oxygen uptake (V̇(O2peak)), respectively, and exercised at 90% V̇(O2peak) until exhaustion. Venous blood samples were collected during the last minute of each submaximal exercise session and immediately after exhaustion. Acute exercise at 40, 70 and 90% V̇(O2peak) induced significant increases in serum dehydroepiandrosterone (DHEA) and free testosterone concentrations in non-athletes. On the contrary, only 90% V̇O2 peak exercise led to an increase in serum DHEA and free testosterone concentrations in athletes. Serum 5α-dihydrotestosterone concentrations increased with 90% V̇(O2peak) exercise in both athletes and non-athletes. Additionally, serum estradiol concentrations were significantly increased at moderate and high exercise intensities in both athletes and non-athletes. These results indicate that in endurance athletes, serum sex steroid hormone concentrations, especially serum DHEA and 5α-dihydrotestosterone concentrations, increased only with high-intensity exercise, suggesting that different responses of sex steroid hormone secretion are induced by different exercise intensities in individuals with low and high levels of physical fitness. In athletes, therefore, high-intensity exercise may be required to increase circulating sex steroid hormone concentrations.

Regulation of local steroidogenesis in the brain and in prostate cancer: lessons learned from interdisciplinary collaboration.

Sex steroids play critical roles in the regulation of the brain and many other organs. Traditionally, researchers have focused on sex steroid signaling that involves travel from the gonads via the circulation to intracellular receptors in target tissues. This classic concept has been challenged, however, by the growing number of cases in which steroids are synthesized locally and act locally within diverse tissues. For example, the brain and prostate carcinoma were previously considered targets of gonadal sex steroids, but under certain circumstances, these tissues can upregulate their steroidogenic potential, particularly when circulating sex steroid concentrations are low. We review some of the similarities and differences between local sex steroid synthesis in the brain and prostate cancer. We also share five lessons that we have learned during the course of our interdisciplinary collaboration, which brought together neuroendocrinologists and cancer biologists. These lessons have important implications for future research in both fields.

Incidence of Total Knee and Hip Replacement for Osteoarthritis in Relation to Circulating Sex Steroid Hormone Concentrations in Women

The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Study subjects (n = 2,621; all women) were recruited in 1990-1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001-2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log-transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50-0.96), and greater log-transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52-0.93). In contrast, greater log-transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05-2.77). A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA.

Abstract A57: Alcohol consumption and plasma sex steroids in premenopausal women

Abstract Purpose: Alcohol consumption is a consistent risk factor for breast cancer, and evidence suggests premenopausal plasma hormones are associated with breast cancer. In this study, we examined the association between alcohol consumption and plasma sex steroid hormones in premenopausal women. Methods: We assessed the cross-sectional association between alcohol intake and circulating sex steroid concentrations among 2,034 premenopausal women in the Nurses' Health Study II (NHSII). Plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, prolactin, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulphate (DHEAS) were measured in samples collected in 1996-99. Estrogens were measured in both the follicular and luteal phases of the menstrual cycle, while androgens were measured in the luteal phase as well as in random samples that were not timed in the menstrual cycle. Average alcohol intake was calculated from semi-quantitative food frequency questionnaires collected in 1995 and 1999. Results: Alcohol consumption was positively association with concentrations of luteal estrone (p-trend<0.0001) and luteal estradiol (p-trend=0.0001). Women who consumed more than 20 grams of alcohol per day, compared with non-drinkers, had higher concentrations of luteal estrone (geometric mean 98.0 vs. 79.9 pg/mL) and luteal estradiol (152.5 vs. 123.3 pg/mL). We did not observe statistically significant associations between alcohol and follicular estrogens, luteal estrone sulfate, testosterone, androstenedione, progesterone, prolactin, DHEA or DHEAS. Conclusion: Alcohol consumption was significantly positively associated with luteal estrogen concentrations, but not with plasma androgen levels, nor estrogens measured in the follicular phase. Thus, luteal estrogen levels may mediate the association between alcohol and breast cancer. Citation Format: Kelly A. Hirko, Susan E. Hankinson, A. Heather Eliassen. Alcohol consumption and plasma sex steroids in premenopausal women. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A57.

Assessment of status of white sucker (Catostomus commersoni) populations exposed to bleached kraft pulp mill effluent

Credible ecological risk assessments often need to include analysis of population-level impacts. In the present study, a predictive model was developed to investigate population dynamics for white sucker (Catostomus commersoni) exposed to pulp mill effluent at a well-studied site in Jackfish Bay, Lake Superior, Canada. The model uniquely combines a Leslie population projection matrix and the logistic equation to translate changes in the fecundity and the age structure of a breeding population of white sucker exposed to pulp mill effluent to alterations in population growth rate. Application of this density-dependent population projection model requires construction of a life table for the organism of interest, a measure of carrying capacity, and an estimation of the effect of stressors on vital rates. A white sucker population existing at carrying capacity and subsequently exposed to pulp mill effluent equivalent to a documented exposure experienced during the period 1988 to 1994 in Jackfish Bay would be expected to exhibit a 34% to 51% annual decrease in recruitment during the first 5 yr of exposure and approach a population size of 71% of carrying capacity. The Jackfish Bay study site contains monitoring data for biochemical endpoints in white sucker, including circulating sex steroid concentrations, that could be combined with population modeling to utilize the model demonstrated at the Jackfish Bay study site for investigation of other white sucker populations at sites that are less data-rich.

Gonadotropin-induced changes in oviducal mRNA expression levels of sex steroid hormone receptors and activin-related signaling factors in the alligator

Oviducts respond to hormonal cues from ovaries with tissue proliferation and differentiation in preparation of transporting and fostering gametes. These responses produce oviducal microenvironments conducive to reproductive success. Here, we investigated changes in circulating plasma sex steroid hormones concentrations and ovarian and oviducal mRNA expression to an in vivo gonadotropin (FSH) challenge in sexually immature, five-month-old alligators. Further, we investigated differences in these observed responses between alligators hatched from eggs collected at a heavily-polluted (Lake Apopka, FL) and minimally-polluted (Lake Woodruff, FL) site. In oviducts, we measured mRNA expression of estrogen, progesterone, and androgen receptors and also beta A and B subunits which homo- or heterodimerize to produce the transforming growth factor activin. In comparison, minimal inhibin alpha subunit mRNA expression suggests that these oviducts produce a primarily activin-dominated signaling milieu. Ovaries responded to a five-day FSH challenge with increased expression of steroidogenic enzyme mRNA which was concomitant with increased circulating sex steroid hormone concentrations. Oviducts in the FSH-challenged Lake Woodruff alligators increased mRNA expression of progesterone and androgen receptors, proliferating cell nuclear antigen, and the activin signaling antagonist follistatin. In contrast, Lake Apopka alligators displayed a diminished increase in ovarian CYP19A1 aromatase expression and no increase in oviducal AR expression, as compared to those observed in Lake Woodruff alligators. These results demonstrate that five-month-old female alligators display an endocrine-responsive ovarian-oviducal axis and environmental pollution exposure may alter these physiological responses.

Nitrate-induced elevations in circulating sex steroid concentrations in female Siberian sturgeon ( Acipenser baeri) in commercial aquaculture

Although nitrate is a ubiquitous component of aquatic environments, and has become a global pollutant in a variety of aquatic systems, it has only recently begun to receive attention for its ability to alter endocrine function. Aquaculture environments with limited water exchange often contain nitrate concentrations far in excess of natural environments, yet nitrate's impact on the reproductive health and endocrine function of commercially important species residing in these environments has not been investigated. Two experiments were conducted evaluating the effects of elevated nitrate on cultured Siberian sturgeon ( Acipenser baeri). The first experiment compared the effects of a 30 day exposure to 11.5 ± 0.36 and 57 ± 2.18 mg/L nitrate-N concentrations on plasma cortisol (F), glucose, 17β-estradiol (E 2), testosterone (T) and 11-ketotestosterone (11-KT) concentrations. The second experiment was similar to the first but evaluated concentrations of 1.5 ± 0.057 and 57 ± 1.52 mg/L nitrate-N. In both experiments, after 30 days of exposure to a given nitrate concentration, blood samples were obtained at time 0, and a portion of those fish were then placed under confinement stress for a period of 6 h to evaluate whether nitrate affects the associated stress response. The fish were bled at 1 h and 6 h during the confinement period. Results revealed that 57 mg/L nitrate-N exposure was associated with an increase in plasma T, 11-KT and E 2 concentrations at time 0, but did not alter the associated stress response defined by elevated plasma cortisol concentrations. An additional measure of the stress response, plasma glucose concentration, however, was altered by nitrate exposure during the 6 h period of confinement stress in Experiment 1, but was not in Experiment 2. These findings demonstrate that nitrate has the potential to disrupt endocrine function and possibly secondary stress responses in cultured Siberian sturgeon.