Neuroendocrine Functions Of PrRP, A Novel Hypothalamic Peptide
Funder
National Health and Medical Research Council
Funding Amount
$183,928.00
Summary
This project investigates the role of a newly discovered chemical (peptide) that is found in a part of the brain called the hypothalamus which regulates the activity of the pituitary gland. The hypothalamus and pituitary gland work together to control many of the body?s essential processes such as growth, metabolism and reproduction. Some human diseases are caused by abnormalities of the hypothalamus and pituitary gland while many other diseases affect the functions of these glands, leading to w ....This project investigates the role of a newly discovered chemical (peptide) that is found in a part of the brain called the hypothalamus which regulates the activity of the pituitary gland. The hypothalamus and pituitary gland work together to control many of the body?s essential processes such as growth, metabolism and reproduction. Some human diseases are caused by abnormalities of the hypothalamus and pituitary gland while many other diseases affect the functions of these glands, leading to widespread complications such as weight loss, wasting, abnormal immune responses, infertility or failure of lactation. While many of the hormones and chemicals of the hypothalamus and pituitary gland have been extensively studied, recent advances in molecular biology have led to the discovery of new chemicals that may have important regulatory functions. One of these newly discovered substances which was named Prolactin-Releasing Peptide or PrRP is the topic of this project. PrRP will be tested in a series of experiments in animals in order to determine how important it is in regulating the pituitary gland, particularly in stress and during lactation which are conditions when PrRP could be secreted. It is hoped that this research will lead to a more detailed understanding of how the reproductive and endocrine system are controlled in humans and to new methods for the manipulation of these systems under normal and disease conditions.Read moreRead less
Do PACAP-containing Neurons In The Hypothalamus Regulate Reproductive Hormone Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$182,559.00
Summary
This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the r ....This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the result that patients have low levels of steroids in their blood and inactive gonads, changes which in themselves lead to other health problems. Because these hormones are essential for normal reproduction, it is possible that PACAP may play an important role in regulating this process, both under normal conditions and in disease. It is hoped that this research will lead to a more detailed understanding of how the endocrine system is controlled in humans and to new methods for the manipulation of the reproductive axis, under normal and disease conditions.Read moreRead less
Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
The Role Of Ghrelin And Growth Hormone Releasing Hormone In The Autocrine Regulation Of Prostate Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in ....Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in regulating GH release. There is growing evidence that the GHRH-GH-IGF axis has a significant role in prostate cancer, but little is known about how this happens. We also have evidence that the ghrelin-GHS-R axis is involved in prostate cancer, as prostate cancer cell lines produce both ghrelin and the receptor through which it acts. Our preliminary studies show that ghrelin enhances cell growth in these cells. GHRH blocking agents (antagonists) are potential treatments for prostate cancer, as they slow the growth of prostate tumours. How they act is unclear, but they might interfere with a locally active GHRH pathway in the prostate. This study aims to explore the role of ghrelin and GHRH in prostate cancer. Since there is an increase in the use of GHRH, GH and-or IGF-I and potentially ghrelin for the treatment of a variety of medical conditions, including some in the aging male, the need for a fuller understanding of the role of this axis in prostate cancer is increasingly important. Such information will lead to a deeper understanding of the actions of ghrelin and GHRH and provide potential opportunities for design of new therapies for prostate and other GH-IGF-responsive tumours.Read moreRead less
Impact Of Progesterone Receptor Subnuclear Localisation On Progesterone Action In Endocrine Target Cells
Funder
National Health and Medical Research Council
Funding Amount
$459,514.00
Summary
Breast cancer affects 10,000 Australian women annually and is a major cause of cancer death. The hormone progesterone, which is produced by the ovaries in women, is responsible for some aspects of the development of the normal breast in women and is also implicated in the development and response of breast and endometrial cancers. In normal cells progesterone acts via a specific protein (or receptor) in the nucleus, and we have shown that this protein accumulates into foci when it is active. We ....Breast cancer affects 10,000 Australian women annually and is a major cause of cancer death. The hormone progesterone, which is produced by the ovaries in women, is responsible for some aspects of the development of the normal breast in women and is also implicated in the development and response of breast and endometrial cancers. In normal cells progesterone acts via a specific protein (or receptor) in the nucleus, and we have shown that this protein accumulates into foci when it is active. We have noticed that in cancers, this accumulation is disrupted, and this is a bad sign for the cancer. As breast cancer develops, it causes many dramatic changes in the structure of cells of the breast, and particularly in the nucleus, which carries the genetic information that programs cancer cell behaviour. The nucleus normally is highly organised into compartments, which carry out different functions of the cell, such as duplication of the DNA, repair of DNA after damage, and switching on and off of particular genes important to the function of the cell. This organisation is altered dramatically in cancer cells, and it seems that this altered organisation is responsible for altered function. In this project we aim to work out what makes the receptor for progesterone form foci, how these foci are involved in the action of progesterone, and how the changed structure of the nucleus changes this process. This project will link the structure of the cell nucleus with the ability of progesterone to switch on or off particular genes, and this will provide the first signposts of how changes seen in cancer cell nuclei are reflected in changed hormonal signalling. Healthy women are regularly exposed to progestins in oral contraceptives and hormone replacement therapy. The known increased risk of breast cancer as a result of exposure to progestins creates an imperative to understand how progesterone may have aberrant effects. This project will address this important health issue.Read moreRead less
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Biomarkers For The Treatment And Prognosis Of Sight-threatening Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$598,305.00
Summary
Diabetic retinopathy (DR) is a highly specific vascular complication of both type 1 and type 2 diabetes, with prevalence strongly related to the duration of diabetes. Clinic biomarkers of DR have become the basis for preventive medicine. In this project, we aim to evaluate possible biomarkers in both Chinese and Australian diabetic populations at different stages of DR. We will also investigate pathological mechanisms and novel drugs to treat DR in animal models.
Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins t ....Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins that bind to SRA in cancer cells, and may well play a critical role in regulating how SRA modulates genes. This project seeks to understand how this family interacts with SRA, the functional effects on breast cancer cells, and the detailed 3-dimensional structure of the family members coupled with SRA. This work will provide novel insight into how SRA regulates steroid hormone action, and may create new potential avenues for developing therapeutics in breast cancer.Read moreRead less