Abstract
The aim of this thesis was to use the possum as an animal model to investigate changes in the expression of transforming growth factor beta 3 (TGF-β3) and TGF-β receptor type III (TGF-βRIII) during seasonal growth and regression of the prostate. In vitro TGF-β1, -β2 and -β3 suppresses the growth of both prostatic epithelial and stromal cells. All three isoforms of TGF-β have been identified in the human prostate. TGF-βRIII is the most abundant TGF-β receptor in many cell types and mediates TGF-β signalling through both Smad and non-Smad signalling pathways. However, the prostatic cells expressing TGF-βRIII have not been identified. The possum has a prostate that is structurally similar to man and significantly exhibits seasonal growth and regression. This study aimed to identify and localise TGF-β3 and TGF-βRIII as well as examine whether the expression of these proteins altered during physiological growth and regression of the possum prostate. This study also provides a preliminary investigation of the possum prostate transcriptome.
Immunoreactive TGF-β3 and TGF-βRIII were identified in the possum prostate. In both periurethral and glandular regions, immunoreactivity of TGF-β3 was greater in the basal and secretory epithelial cells relative to the stromal compartment. TGF-βRIII was immunolocalised to the basal and secretory epithelial cells of periurethral and glandular acini, with no immunostaining in the stromal tissue. In the cranial region of the prostate, expression of the mature form of TGF-β3 and TGF-βRIII changed during seasonal growth and regression with expression decreasing during prostate growth at the main breeding period and increasing at the onset of prostate regression. No significant changes in expression were observed in the caudal region of the prostate.
Expression changes in TGF-β3 and TGF-βRIII appeared inversely related to prostate weight. Markers of cell proliferation and apoptosis were used to explore the mechanisms underlying changes in weight. Increased cell proliferation occurred prior to and during the main breeding period, while the number of proliferating cells declined during the non-breeding period. Increased apoptosis was only observed during the main breeding period in the cranial region of the prostate. As with prostate weight, TGF-β3 and TGF-βRIII expression was reduced during periods of cell proliferation. These findings support a role for TGF-β3 and TGF-βRIII in inhibiting cell proliferation in the possum prostate.
In conclusion, this thesis provides evidence that expression of TGF-β3 and TGF-βRIII is decreased during periods of physiological growth and increased during regression in the possum prostate. These findings support a role for TGF-β3 as a negative growth regulator in the prostate. The localisation of these proteins was both region and cell specific in the possum providing a possible animal model for the study of the regulation of prostate growth. Further studies are required to determine whether treatment with TGF-β3 is able to modulate prostate growth in vivo.