Thesis (M.Sc.) (Hons.) -- University of Western Sydney, 2002. / A thesis submitted to the University of Western Sydney in fulfillment of the requirements for admission to the [degree of] Masters of Science (Honours). Bibliography : leaves 156-163.

Thesis (M.S.)--Eastern Illinois University, 2009. / Includes bibliographical references (leaves 23-26).

Thesis (Ph. D.)--Carleton University, 2001. / Includes bibliographical references. Also available in electronic format on the Internet.

Thesis (Ph. D.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaves 95-104). Also available on the World Wide Web.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 110-124).

Thesis (M.S.) -- Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 151-169).

Thesis (Ph. D.)(Microbiology)--University of Pretoria, 2007. / Includes bibliographical references. Available on the Internet via the World Wide Web.

An alarming reduction in the numbers of several species of seals in the Baltic Sea was observed during the second half of the 1900s. Organochlorines, particularly PCBs, were found to cause the decline, inducing sterility and severe bone loss. If bone tissue is affected by PCBs, bone could be used as a biomarker for exposure to environmental contaminants. To isolate the effects of PCBs from other factors, experimental studies have been conducted on model species, such as mink. In this study, 58 mink femurs from three different treatment groups and one control group were analysed. Altogether 14 different parameters were measured using peripheral quantitative computed tomography (pQCT). Mink treated with a low dose of PCBs develop increased content, area and thickness of cortical bone. Mink treated with a high dose of PCBs do not show the same effects but have a cortical area similar to that of non-exposed animals. The trabecular density and content is increased in all groups that have been exposed to PCBs. The observed effects may be the result of dioxin-like PCBs binding to the aryl hydrocarbon receptor (AhR). The activation of AhR leads to disruptions in endocrine systems, that in turn impacts bone modelling and remodelling. However, other pathways cannot be ruled out, including the effects of non-dioxin-like PCBs. Further analyses are needed in order to fully understand how PCBs affect bone tissue properties.

There is growing concern that the health of many species, including humans, may be threatened by an increasing burden of environmental contaminants. Many researchers around the world have made discoveries demonstrating endocrine activity in an array of contaminants to which humans and wildlife may be exposed. Although much of the focus has been upon interference with estrogen activities, there is growing evidence for interaction with thyroid, androgen and other endocrine axes. This study investigates the potential of a selection of environmental contaminants, including PCBs, pulp mill by-products, pesticides, and alkylphenols, to interfere with endocrine processes. Using tissue culture assays, we have investigated the ability of these compounds to interfere with steroid hormone signalling pathways and have focused on the underlying mechanism of androgenic effects observed through further in vitro assays. A transgenic mouse model was used to explore the impact of compounds of particular interest upon the development and function of androgen regulated tissues in vivo. Several of the test compounds possessed endocrine activity, most frequently manifest as antagonism of the androgen receptor (AR). Amongst the pesticides tested both the o,p′- and p,p′-isomers of dichlorodiphenyltrichloroethane (DDT) and p,p′-dichlorodiphenyldichloroethylene (DDE) were AR antagonists. Nonylphenol and a short chain ethoxylate (N-10) as well as four Aroclor mixtures and a set of congener components selected from them were also found to antagonise AR. Only hexachloroberizene and black liquor, a pulp mill by-product, exhibited androgenic effects in vitro . Estrogen receptor was antagonised by β-endosulfan and p,p′-DDE, while o,p ′-DDT, nonylphenol and octylphenol all acted as estrogen mimics. The glucocorticoid receptor was antagonised by β-endosulfan, while being stimulated by o,p′-DDT, the alkylphenol ethoxylate N-100 and PCB congener 42. Nonylphenol, Aroclor 1254 and one of the PCB congeners were tested by oral administration in mice and all produced physiological effects, with Aroclor 1254 in particular exhibiting clear anti-androgenic properties in vivo. Nonylphenol caused an elevation in serum thyroid hormone along with an increase in testis size and anogenital distance. In addition, the nonylphenol treatment increased the expression of an androgen responsive CAT reporter gene that is expressed specifically in the prostate. The PCB mixture Aroclor 1254 caused a decrease in prostate weight, and CAT reporter gene expression but precocious maturation of the prostate gland. In contrast the congener PCB 42 had no significant effects upon the prostate but caused increased testis weight and impacted on spermatogenesis in the epididymis. These results emphasize the sensitivity of the endocrine system and the diverse physiological functions which it regulates. They also demonstrate the ligand promiscuity of the steroid receptors and reinforce the need to evaluate the endocrine potential of substances humankind introduces into the environment. / Graduate