We exposed a native endangered species, bonytail chub (Gila elegans), to graded concentrations of secondarily-treated effluent. At the end of each treatment period, we collected water from all raceways and samples were analyzed for the presence of 83 organic wastewater compounds. We extracted blood plasma from control and treatment fish in each raceway and samples were analyzed for hormones, 17β-estradiol and 11-ketotestosterone, and the egg yolk protein, vitellogenin.17β-estradiol concentrations were consistently lower in treatment females than those detected in control females. The 17β-estradiol and vitellogenin concentrations were always higher in treatment males than those found in control males. Concentrations of 11-ketotestosterone were consistently lower in treatment males than those detected in control males.Endocrine disrupting effects occurred in male and female fish exposed to low concentrations of effluent. Changes in hormone levels suggested a feminizing effect in treatment male fish and an androgenizing effect in treatment female fish.

Human pregnancy is characterized by significant increases in central ventilatory drive and perceived respiratory discomfort (breathlessness). The physiological mechanisms of hyperventilation and breathlessness in pregnancy remain largely unknown and understudied. Objective: The main purpose of this research was to elucidate the mechanisms of maternal hyperventilation, and to systematically examine the contribution of alterations in central ventilatory drive, static/dynamic respiratory mechanics and their interaction with respect to the intensity of perceived breathlessness during exercise in pregnancy. General Methods: Experiments were conducted between 34-38 wks gestation and again 4-5 months post-partum in a total of 35 healthy, young women. A comprehensive mathematical model of ventilatory control was used to examine the role of alterations in wakefulness and central chemoreflex drives to breathe, acid-base balance and female sex hormones in maternal hyperventilation. The effects of pregnancy on detailed ventilatory (breathing pattern, airway function, operating lung volumes, esophageal pressure-derived indices of respiratory mechanics) and perceptual (breathing and leg discomfort) responses to incremental cycle exercise to the limits of tolerance were also examined. Results: Maternal hyperventilation resulted from a complex interaction between alterations in arterial and central acid-base balance and other factors that directly affect ventilation, including increased wakefulness and central chemoreflex drives to breathe, increased metabolism and decreased cerebral blood flow. Mechanical adaptations of the respiratory system, including recruitment of resting inspiratory capacity and reduced airway resistance, accommodated the increased demand for tidal volume expansion during exercise in pregnancy, while preserving effort-displacement and breathlessness-ventilation relationships. Variation in the severity of gestational breathlessness could not be explained by respiratory mechanical/muscular factors, but ultimately reflected variation in the amplitude of maternal hyperventilation and temporal desensitization to the sensory consequences of increased ventilation. Conclusion: Our results indicated that 1) the hyperventilation and attendant hypocapnia/alkalosis of pregnancy can be explained by alterations in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow; 2) mechanical adaptations of the respiratory system obviated the anticipated rise in perceived breathlessness for a given ventilation during exercise in pregnancy, and helped to ensure that peak aerobic working capacity was admirably preserved, even in late gestation; and 3) gestational breathlessness ultimately reflected the normal awareness of increased ventilation and contractile respiratory muscle effort. / Thesis (Ph.D, Kinesiology & Health Studies) -- Queen's University, 2008-08-28 16:01:40.78

Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies. Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy. Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02], ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07], ptrend=0.07). The inverse association between IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96], ptrend=0.03). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology. The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements. Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.

1a,25-Dihydroxyvitamin D3 (1a,25(OH)2D3) is a major functional metabolic form of vitamin D. 1a,25(OH)2D3 has drawn increasing attention due to its functions in addition to maintaining calcium phosphate homeostasis. It directly regulates mineralization by osteoblasts, matrix production and remodeling by chondrocytes, and contraction of cardiomyocytes. 1a,25(OH)2D3 and its analogues have shown beneficial effects in treating multiple sclerosis, diabetes and various types of cancer. In order to maximize the pharmaceutical potential of 1a,25(OH)2D3, a better understanding its cell signaling pathway is necessary. 1a,25(OH)2D3 regulates osteoblasts through both classical nuclear vitamin D receptor (nVDR) mediated genomic effects and plasma membrane receptor-mediated rapid responses. The identity of the plasma membrane receptor for 1a,25(OH)2D3 is controversial. Protein disulfide isomerase associated 3 (Pdia3) has been hypothesized as one of the putative plasma membrane receptors for 1a,25(OH)2D3. The overall goal of this thesis was to understand the general role and the molecular mechanism of Pdia3 in 1a,25(OH)2D3-initiated rapid responses, and to determine the role of Pdia3 and its dependent signaling in osteoblast biology. The results show that Pdia3 is required for membrane-mediated responses of 1a,25(OH)2D3. Moreover, both Pdia3 and nVDR are critical components of the plasma membrane receptor complex for 1a,25(OH)2D3. Finally, Pdia3 and signaling via Pdia3 regulate osteoblast differentiation and mineralization. Taken together, this study demonstrates the role of Pdia3 in rapid responses to 1a,25(OH)2D3 and osteoblast biology, reveals the unexpected complexity of the 1a,25(OH)2D3 plasma receptor complex and opens the new target, Pdia3, for pharmaceutical application and tissue engineering.

Relationships between the steroid hormones estradiol (E2), testosterone (T), cortisol (CRT) and dehydroepiandrosterone-sulfate (DHEAS), memory and mood were investigated in men, in women estrogen-users and non-users, and in patients with Alzheimer's Disease (AD). In Study 1, 72 year-old healthy men and women estrogen-users performed better than estrogen non-users on Forward and Total Digit Span, which test attention and short-term memory, concomitant with their higher E2 levels. The estrogen-users performed better than the men and the non-users on Delayed Selective Reminding, a test of explicit verbal memory. Men and women with higher CRT levels performed worse on several explicit verbal memory tests compared to those with lower endogenous, CRT levels. In Study 2, male patients with AD performed better than estrogen non-using women with AD on several everyday memory tests, and women estrogen-users with AD performed similarly to the men. Both the men and estrogen-users had higher levels of E2 than the non-users. AD patients with higher endogenous levels of DHEAS performed better than those with lower levels on several everyday memory tests, and AD patients with higher CRT levels were impaired on one aspect of everyday spatial memory, Route Recall. In Study 3, no differences in hormone levels between AD patients and age-matched healthy elderly controls were found. The AD patients were most severely impaired on tasks involving explicit verbal recall compared to healthy controls, and least impaired on short-term memory and concentration tasks. The AD patients reported more dysphoric mood and mental dulling symptoms than healthy age-matched controls, but they did not report feeling less positive about the future. Taken together, these results suggest that higher levels of DHEAS and E2 are related to better memory performance in both healthy elderly men and women and in patients with AD, and higher CRT levels are associated with poorer explicit verbal memory performanc

Sea Turtles are long-lived marine reptiles that have existed for more than 150,000 years. All seven turtle species extant today are characterised as endangered by the World Conservation Union Red List of Threatened Species. This PhD thesis investigates aspects of endocrinology and toxicology in green (Chelonia mydas) (Peninsular Malaysia) and flatback (Natator depressus) (Curtis Island, Queensland, Australia) turtles. This thesis aimed to identify if toxicants have an affect on reproduction and development in marine turtles. A high affinity steroid binding protein showing an affinity for testosterone and oestradiol was identified and described in nesting C. mydas and the thermal profile of sex steroid binding proteins in C. mydas was studied. This is the first study that has investigated sex steroid binding proteins in marine turtles. A sex steroid binding protein was also observed in male and female hatchling C. mydas and the effect of temperature on sex steroid binding proteins was investigated. This new, minor-invasive method of sex identification shows that different sex steroid binding proteins could reflect different hormonal patterns in female and male hatchling C. mydas. The steroid and metabolites profiles in nesting C. mydas (Peninsular Malaysia) and N. depressus (Curtis Island, Queensland) were established. Progesterone levels were the highest followed by testosterone, oestrone and dihydrotestosterone levels. The significant role of oestrone in nesting sea turtles was verified. The elevated concentrations of corticosterone, thyroxine, glucose and triglyceride indicated high metabolic demands placed upon C. mydas and N. depressus during nesting activities. The metabolite profiles and hormone concentrations were investigated to determine whether there was any relationship between hormonal changes during nesting activities in C. mydas and N. depressus. A methodology to measure heavy metal concentrations in the blood and eggs of N. depressus was developed. Moreover, this was the first time that tin compound derivatives have been identified in marine turtles in Australia. A complex heavy metal profile was identified in eggs. It is suggested that eggs may be an important, practical and reliable indicator of environmental contamination in nesting marine turtles. Pesticides were measured in the blood and eggs of N. depressus. Organochlorine and polychlorinated biphenyl concentrations were measured in the blood in N. depressus. Traces of OCs and PCBs were detected in eggs of N. depressus. Furthermore, the effects of heavy metals in developing C. mydas of both sexes are presented. During development, it was investigated whether heavy metal concentrations were affected by age, gender or the different clutch in C. mydas. The effect of a variety of toxicants (i.e. pesticides and heavy metals) on the sex steroid binding protein properties was investigated in nesting C. mydas. This important study identifies mechanisms by which toxicants may exert a physiological effect upon sex steroids (i.e. testosterone and oestradiol) in nesting turtles. The toxicants were studied at a wide range of concentrations. Some toxicants were shown to weaken or abolish the association of the testosterone and/or oestradiol binding proteins in nesting C. mydas. Correlations were observed between heavy metal concentrations found in blood and eggs and steroid and metabolite levels in nesting N. depressus. Zinc which was previously measured in the blood was positively correlated with testosterone concentrations in nesting N. depressus. Chromium which was found in eggs was negatively correlated corticosterone concentrations. Manganese was the only heavy metal (measured in eggs) which was negatively correlated with progesterone and positively correlated with triglyceride concentrations in nesting N. depressus. Finally, a quantified histological method was developed to determine the sex in C. mydas hatchlings by investigating specific histological criteria. A number of “undetermined sex” hatchlings were verified and it is hypothesised that abnormal reproductive development is related to the presence of environmental contaminants previously found in the studied C. mydas population of Peninsular Malaysia.

Bibliography: leaves 182-210 / vii, 210 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--Dept. of Obstetrics and Gynaecology, University of Adelaide, 1985

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 1988. / Includes bibliographical references (leaves 165-175).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 134-155).

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 4 uppsatser.