This study is investigating an autoimmune disease called lymphocytic hypophysitis, involving the master gland in the body, the pituitary. It often affects pregnant women and is under diagnosed. The aim of our study is to determine the cause of this disease and its unexplained link with pregnancy. We are also working on a new diagnostic test which will enable doctors to confirm the diagnosis by serological means. At present, invasive pituitary biopsy is needed. Whilst developing this new test, we ....This study is investigating an autoimmune disease called lymphocytic hypophysitis, involving the master gland in the body, the pituitary. It often affects pregnant women and is under diagnosed. The aim of our study is to determine the cause of this disease and its unexplained link with pregnancy. We are also working on a new diagnostic test which will enable doctors to confirm the diagnosis by serological means. At present, invasive pituitary biopsy is needed. Whilst developing this new test, we have identified three proteins and their genes. This information may have major implications for the study of pituitary gland function.Read moreRead less
Functional Analysis Of The Notch Signalling Pathway In The Differentiation And Maintenance Of Pituitary Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,320.00
Summary
Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow ....Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development, metabolism and milk production, are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone secreting cells to arise. Changes in these pituitary formation genes results in underdevelopment of the pituitary in newborn babies. In severe cases, where the pituitary has failed to form completely (panhypopituitarism), these babies are extremely ill and in some instances do not survive. We are studying the genes that belong to the Notch signalling pathway. These genes are important regulators of cell differentiation during the development of the brain, skin, bone and many other tissues. However, the role of the Notch signalling genes in pituitary development is not known. We have shown for the first time that these genes are active during pituitary development. To test the function of these genes in the pituitary, we will generate mouse models that either lack or inappropriately activate these genes. Our results will provide insight into the role of Notch Signalling genes in pituitary development in mice and humans. In this project, we also hope to identify cells in the pituitary that are able to give rise to multiple hormone secreting cell types. These stem cells are of significant clinical importance as they provide an avenue for the development of novel therapies for pituitary disorders in humans, based on the replacement of defective pituitary tissue with functional stem cell derived tissue.Read moreRead less
Functional Analysis Of A Novel Genetic Mouse Model For Congenital Growth Hormone Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$519,131.00
Summary
Pituitary Hormone deficiency is not uncommon and is associated with poor growth, metabolism and fertility. Some cases of this disorder arise due to genetic changes that compromise the ability of the pituitary gland to make or secrete growth hormone (GH). Using cutting-edge genomics technology, we have generated a new genetic mouse model of GH deficiency. The aim of this project is to understand the function of this novel GH _regulating gene in mice and in humans.
Enrichment, Differentiation And Functional Analysis Of Growth Hormone Progenitor Cells From The Adult Mouse Pituitary
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH de ....Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH deficiency is treated by daily injections of growth hormone at a cost of $30,000 to $50,000 per patient per annum. However, even with daily injections and despite the cost, it is difficult to mimic the naturally fluctuating hormone levels in the body, resulting in incomplete growth rescue. Long term injections also have severe side effects that can lead to cardiovascular problems, abnormal bone density, diabetes and cancers of various types. To overcome the disadvantages of hormone therapy we are investigating a new cell replacement therapy to treat GH deficiency. This approach requires knowledge about the mechanism by which GH-secreting cells are generated and maintained in the adult pituitary. For the first time, we have isolated a type of progenitor (unspecialised) cell from adult mouse pituitary that is capable of dividing and generating GH-secreting cells. Our current research aims to further purify these cells and to show that they are capable of secreting GH in response to biologically relevant signals. In addition, we will test whether these cells can grow and develop into functional cells when introduced into mice. In particular, we will test whether the progenitor cells can rescue dwarfism using a mouse model of GH deficiency. This pioneering study will provide the first insight into the possibility of cell therapy for the pituitary, and may ultimately lead to the development of better therapies for patients with GH deficiency.Read moreRead less
Functional Analysis Of The X-linked Hypopituitarism (XH) Gene SOX3
Funder
National Health and Medical Research Council
Funding Amount
$331,000.00
Summary
Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development and metabolism are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone-secret ....Many of the processes that are essential for normal bodily function such as growth, the ability to cope with stress, sexual organ development and metabolism are controlled by the pituitary gland. This organ is located at the base of the brain and regulates these bodily functions through the release of six different hormones. Formation of the pituitary gland occurs during development of the foetus. This process requires a specific set of genes that shape the pituitary and allow the hormone-secreting cells to arise. Changes in these pituitary formation genes results in dysfunction of the pituitary (hypopituitarism) in newborn babies. In severe cases, where the pituitary has failed to form completely, these babies are extremely ill and in some instances do not survive. We are studying families with an inherited form of hypopituitarism in which only male children are affected. This disorder is due to the presence of an extra piece of genetic material (DNA) on the X chromosome. We have recently discovered that one of the duplicated genes, SOX3, causes this disorder. The overall aim of this proposal is to understand how SOX3 causes hypopituitarism by generating a mouse model for this disorder. Analysis of this mouse model will help us to understand the clinical features of hypopituitarism and may allow us to identify previously uncharacterised anatomical defects associated with this disorder. Ultimately,we hope to develop new and improved therapies for hypopituitarism using this mouse model.Read moreRead less