Phodopus campbelli is a naturally biparental dwarf hamster with males so paternal they will act as midwives during the birth of their litter. The hormonal regulation of parental behaviour has been well established in many species. However, to date, no causal mechanism for the extensive paternal behaviour displayed by male P. campbelli has been discovered. Recently, activity at the progesterone receptor has been shown to inhibit infant-directed behaviour in male mice. Therefore, the first study in this thesis was carried out to determine if antagonism of the progesterone receptor (PR) would enhance infant-directed care behaviour in naïve P. campbelli males. Despite detectable serum progesterone concentration in males, PR antagonism did not alter progesterone concentration, nor did it alter infant-directed behaviour in males with antagonized PR in adulthood. A slight increase in the latency to retrieve a pup seen in males with antagonized PR during adolescence suggests that there may be a developmental effect of PR activity on infant-directed behaviour in adulthood. Neonatal male rats express high levels of PR in brain regions important for parental behaviour. Since hormones can act very early in life to organize adult behaviour, the second study was carried out to determine if progesterone acting much earlier than adolescence is important in the regulation of paternal behaviour in P. campbelli adulthood. Males were treated daily for the first week of life with transdermal progesterone, which increased neonatal serum progesterone concentration fivefold. Despite the significant increase in progesterone (and therefore presumably activity at the PR), male behaviour in three different stages of adulthood (sexually naïve, during the birth of the male’s first litter, and in new fatherhood) towards pups was not altered. Measures of paternal contribution such as pup weight throughout the lactational period were altered by progesterone treatment during the neonatal period, but litter quality was ultimately high in both groups. Therefore, activity at the PR in adulthood, puberty, or during the neonatal period does not inhibit paternal behaviour in the naturally biparental hamster, P. campbelli. Thus, progesterone and its receptor do not organizationally or activationally regulate paternal behaviour in P. campbelli. / Thesis (Master, Biology) -- Queen's University, 2009-09-04 13:23:18.733

Mammary gland development is controlled by hormones such as progesterone and prolactin, which activate a genomic regulatory network. Identification of the components and regulatory links that comprise this network will provide the basis for defining the network's dynamic response during normal development and its perturbation during breast carcinogenesis. This thesis investigates two molecules in detail, Elf5 and KIBRA, which were identified as potential prolactin targets in a transcript profiling screen for key members in this genetic program of mammary morphogenesis. We examined the effect of expression of Elf5, a transcription factor critical in alveolar differentiation, in a 3D culture model of non-transformed mammary epithelial MCF-10A cells. We discovered that Elf5 expression was selectively repressed over time in these cells when cultured on a basement membrane, and that Elf5 overexpression disrupted the architecture of acini resulting in luminal filling. This occurred due to an increase in the expression of epidermal growth factor receptor (EGFR) with repressed the induction of the pro-apoptotic molecule, Bim. We also observed that Elf5 is up-regulated with progesterone treatment, and that suppression of Elf5 expression in T47D breast cancer cells inhibits proliferation. Data obtained from the suppression of Elf5 expression in the presence of progesterone suggested that the role played by Elf5 in the Pg signalling pathway in T47D cells is relatively minor, and that rather than being a major downstream factor, the induction of Elf5 expression is utilised more to influence and potentiate other signalling pathways, such as the Prl pathway. We characterised expression of KIBRA in the mammary gland and breast cancer cell lines, and observed that KIBRA was also up-regulated with progesterone treatment. Using a bioinformatic approach, we identified the tyrosine kinase receptor DDR1 as a binding partner of KIBRA. We have demonstrated that the WW domains of KIBRA bind to a PPxY motif in DDR1, and that these molecules dissociate upon treatment with the DDR1 ligand, collagen. Finally, overexpression and knockdown studies demonstrate that KIBRA promotes the collagen-stimulated activation of the MAPK cascade. Thus KIBRA may play a role in how the reproductive state influences the mammary epithelial cell to respond to changing cell-context information, such as experienced during the tissue remodelling events of mammary gland development. Overall, the data presented in this thesis contributes to our growing knowledge of the genetic program responsible for mammary development and carcinogenesis.

Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Michigan State University. Cell and Molecular Biology Program, 2008. / Title from PDF t.p. (viewed on March 30, 2009) Includes bibliographical references (p. 174-178). Also issued in print.

Thesis (Ph. D.)--Biology, Georgia Institute of Technology, 2005. / Choi, Jung, Committee Chair ; Tornabene, Thomas, Committee Member ; Chernoff, Yuri, Committee Member ; Hall, Dwight, Committee Member ; Doyle, Donald, Committee Member. Includes bibliographical references.

Thesis (Ph. D.)--Lehigh University, 1996. / Includes vita. Includes bibliographical references (leaves 78-90).

Thesis (doctoral)--University of Tampere, 1987. / Includes bibliographical references (p. 42-56).

Thesis (Ph. D.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains viii, 130 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

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

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains vii, 87 p. : ill. Includes abstract. Includes bibliographical references.