The role of thyroid-stimulating hormone (TSH) in the regulation of peripheral thyroid function in non-mammalian species is still poorly understood. Thyroxine (T₄), the principal hormone released from the thyroid gland in response to TSH stimulation, circulates with a robust daily rhythm in the sciaenid fish, red drum. Previous research has suggested that the red drum T₄ cycle is circadian in nature, driven by TSH secretion in the early photophase and inhibited by T₄ feedback in the early scotophase. To determine whether TSH is produced in a pattern consistent with driving this T₄ cycle, I developed quantitative real time RT-PCR (qPCR) techniques to quantify the daily cycle of expression of the pituitary TSH subunits GSU[alpha], and TSH[beta]. I found that pituitary TSH expression cycled inversely to, and 6-12 hours out of phase with, the T₄ cycle, consistent with the hypothesis that TSH secretion drives the T₄ cycle. To examine the potential role of deiodinases in negative feedback regulation of this TSH cycle, I also utilized qPCR to assess the pituitary expression patterns of the TH activating enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner ring deiodinase (Dio3). Whereas Dio2 was not expressed with an obvious daily cycle, Dio3 was expressed in the pituitary mirroring the TSH cycle. These results are consistent with T₄ negative feedback on TSH and suggest that TH inactivation by pituitary cells is an important component of the negative feedback system. To further examine the TH regulation of this Dio3 cycle, I developed an immersion technique to administer physiological doses of T₃ and T₄ in vivo. Both hormones persist in static tank water for at least 40 hours. Immersion in 200ng/ml T₄ significantly increased both plasma T₄ and T₃ within physiological ranges above control at 4.5 hours. Immersion in 100ng/ml T₃ increased plasma T₃ within physiological ranges over control by 22 hours while significantly decreasing plasma T₄ below control, presumably through inhibition of TSH secretion. T₄ also significantly inhibited the expression of the TSH [alpha] and [beta] subunits at 4.5 and 22 hours of immersion whereas T₃ immersion significantly inhibited the expression of the [alpha] and [beta] subunits of TSH by 22 hours. Both Dio2 and Dio3 expression were significantly diminished by T3 and T₄ at 22 hours. Inhibition of circulating THs with the goitrogen methimazole significantly increased the expression of TSH. These results indicate that both T₄ and T₃ are capable of negative feedback regulation of TSH expression in red drum on a time scale consistent with the T₄ daily cycle, and further support Dio3 destruction of THs in the pituitary, potentially regulated by circulating T₄, as a critical component of negative feedback on TSH. This study supports the importance of central mechanisms acting through pituitary TSH secretion in regulating thyroid function in red drum.

Doctor of Philosophy(PhD) / The experience of persistent fatigue after breast cancer treatment is estimated to affect approximately one in four women, but fatigue development and factors associated with cancer-related fatigue are poorly understood. Gaining a better understanding of these issues is important because persistent fatigue after radiation therapy can be a debilitating experience for cancer survivors. The objectives of this study were: (1) to determine fatigue prevalence in women with breast cancer at standardised timepoints after radiation therapy; (2) to investigate the relationships between fatigue, salivary cortisol rhythm and thyroid function; (3) to investigate the amount of radiation dose received by the thyroid gland in different radiation therapy treatment techniques; and (4) to investigate the relationship between irradiation of the thyroid, thyroid function and fatigue. Participants in this research were women diagnosed with non-metastatic breast cancer and all were referred for adjuvant radiation therapy treatment. One cohort of participants (n = 48) was assessed prior to the start of radiation therapy and then six months after treatment, and a second cohort (n = 15) was assessed at six months and then at 12 months after treatment. Behavioural assessments included questionnaires that measured the level of multidimensional fatigue (MFSI–SF), the degree of fatigue and depression symptoms (SPHERE–12), impact that fatigue had on participants’ functioning (FIS) and aspects of quality of life (EORTC QLQ–C30). Biological assessments included a three day measurement of salivary cortisol rhythm and an assessment of thyroid function (TSH, free T4 and free T3). Radiation doses to the thyroid gland were determined from participants’ treatment plans. Six months after completing adjuvant radiation therapy, women receiving treatment for breast cancer experienced significant improvements in emotional fatigue, role functioning and social functioning. High fatigue levels were prevalent in 29% of women at six months and 33% of women at 12 months after treatment, but newly developed fatigue that was not present before treatment was only found in 5% of participants. There were no significant changes in cortisol rhythm over time or between fatigued and non-fatigued participants; however, significant positive correlations were found between fatigue and morning cortisol. Regarding thyroid function, significant decreases in free T4 hormone levels were seen from six months to 12 months after radiation therapy with larger decreases in free T4 levels being related to higher fatigue. Radiation doses to the thyroid gland were significantly higher in participants who received treatment to the regional lymphatics with a supraclavicular fossa radiation field compared to participants who received localised treatment to the breast or chest wall only. In the former, changes in thyroid function were observed, as were relationships between mean radiation dose to the thyroid and thyroid function.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (M.Sc.)--York University, 2006. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR29625

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2006. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available online.

Thesis (Ph. D.)--University of Florida, 2004. / Title from PDF title page (viewed on July 3, 2005). Includes vita. Includes bibliographical references (p. 161-178).

Thesis--Catholic University of America. / Bibliography: p. 25-29.