Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / "The objectives of this thesis were to characterise the effects fo AR-targeting agents on the growth of prostate cancer cells and to determine whether combining these agents to target the AR (androgen receptor) at more than one level in the signalling pathway would provide a more complete block of androgen signalling and prostate cancer cell growth." --p. v. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289482 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine,2006

Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / "The objectives of this thesis were to characterise the effects fo AR-targeting agents on the growth of prostate cancer cells and to determine whether combining these agents to target the AR (androgen receptor) at more than one level in the signalling pathway would provide a more complete block of androgen signalling and prostate cancer cell growth." --p. v. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289482 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine,2006

Thesis (Ph.D.)--Auburn University, 2005. / Abstract. Includes bibliographic references.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file.

Thesis (Ph. D.)--Ohio State University, 2004. / Document formatted into pages; contains xxviii, 261 p. Includes bibliographical references (p. 141-149). Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 July 6.

Thesis (M.S.)--Boise State University, 2009. / Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (a) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (b) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggest that the action of local sex hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogens at the time of parturition, the role of androgens has received less scrutiny. The overarching aim of this thesis was to investigate the potential roles of androgens in myometrial biology at the time of pregnancy. We examined both the genetranscription dependent (genomic) and independent (non-genomic) action of androgens on the uterine smooth muscle, employing in vitro, ex vivo, and in vivo approaches. We found that the androgen receptor (AR) mRNA was significantly increased in the myometrium during labour when compared to the term non-labouring myometrium. Our gene expression studies revealed that ligand-dependent AR signalling in the myometrium might play a role in regulation of uterine smooth muscle cell contractility. We explored the effect of androgens on contraction of uterine smooth muscle strips obtained from both human myometrial biopsies collected at term and murine uterine horns. We found that testosterone (T) and dihydrotestosterone (DHT) in a range of 10-100 μM concentrations rapidly relaxed spontaneous and oxytocin-initiated contractions. The relaxant effect was not mediated by the classical intracellular AR nor was cell-surface initiated as shown by experiments employing a specific AR antagonist (flutamide) and a cell-surface impermeable androgen (TBSA). We investigated whether the relaxant effect was specific to androgens or a generic effect of sex hormones. We demonstrated that both estradiol (E2) and progesterone (P4) were also capable of relaxing the human and murine myometrium at the same dose range. In addition, a sex hormone “cocktail” (all four sex hormones combined at 10 μM dose each) mimicked the relaxant effect that each individual sex hormone elicited at a 40 μM dose, implying that the effect was possibly attributable to the steroid structure of the sex hormones. To study the underlying molecular events that mediate the relaxant effect of sex hormones observed ex vivo, we employed two human myometrial cell lines namely PHM1-41s and UtSMCs. We demonstrated that the androgen-induced relaxation in vitro was not induced by cell death but was mediated by a physiological mechanism whereby incubation with the androgen impaired the stimulated-Ca2+ entry into the uterine myocytes, which in turn resulted in poor phosphorylation of myosin light chain protein. Finally, we conducted a pilot study to explore the hypothesis that administration of androgen could relax the uterine muscle in vivo. We utilised a mouse model of infection-induced preterm labour, where infection was induced by intrauterine administration of liposaccharide (LPS) on day 17 of murine pregnancy. Our preliminary data showed that intrauterine administration of DHT on day 17 did not significantly reduce the rate of LPS-induced preterm birth in the doses tested in this study. In conclusion, the androgen-induced in vitro tocolysis appears to be sex hormone-specific rather than androgen-specific. Therefore, sex hormones might have the potential to be used for effective in vivo tocolysis to inhibit premature-initiated contractions. Our investigation of the androgen-dependent signalling in the myometrium contributed to the development of novel hypotheses regarding the role of androgens in the regulation of the phenotypic transition of MSMCs during pregnancy. These hypotheses remain to be confirmed in future studies.

It has been asserted that androgynous individuals are both competent and flexible and that, as such, they should be most likely to be authoritative parents (highly demanding/highly responsive) (Spence & Helmreich, 1978). However, studies examining the association between psychological androgyny and this optimal parenting strategy (Baumrind, 1982; Spence & Helmreich, 1978) have reached conflicting conclusions. The position taken in this study is that there is a logical association between androgyny and authoritative parenting at the construct level, but that the component of androgyny critical to this link is functional flexibility (the ability to appropriately deploy both masculine and feminine attributes across multi-interpersonal domains) rather than the simple possession of both masculine and feminine traits per se. In view of this argument, earlier studies share a significant limitation. Their operational definitions of androgyny fail to reflect the functional flexibility aspect of the construct definition, thus allowing individuals who possess both masculine and feminine traits but who are not functionally flexible to be classified as androgynous. This study had two objectives. The first was to retest Spence and Helmreich's (1978) hypothesis that androgyny is positively related to authoritative parenting using a measure which would assess functional flexibility. The second objective was to demonstrate that authoritative parenting requires flexibility with respect to a whole range of interpersonal abilities rather than simply masculine and feminine attributes. A sample of 96 mothers with children between the ages of 7 and 12 were asked to complete a battery of questionnaires which included Bern's (1974) Sex Role Inventory (BSRI), Paulhus and Martin's (1987) Battery of Interpersonal Capabilities (BIC), and the Block (1965) Childrearing Practices Report: Q-Sort (CRPR). Contrary to what was expected, neither androgyny nor flexibility with respect to the whole range of interpersonal attributes was positively associated with authoritative parenting. Certain problems with the content of the parenting measure may have contributed to the lack of association. To minimize some of the problems with its content the method of using the parenting Q-sort was revised. The new analyses involved categorizing mothers according to warmth and demandingness--a method similar to that used in earlier studies. In these further analyses few significant differences in parenting style were found between androgynous mothers and other mothers. The most notable difference arose when the sex of the child was considered. Although, overall, androgynous mothers were not more likely to be bad parents, they were more likely than other mothers to be permissive with their sons. / Arts, Faculty of / Social Work, School of / Graduate

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