The Physiological And Pathophysiological Roles Of Melanotransferrin
Funder
National Health and Medical Research Council
Funding Amount
$227,485.00
Summary
Melanotransferrin (MTf) is a membrane bound molecule that was originally identified in the malignant melanoma skin cancer and other tumours. Interestingly, MTf has many similarities to the serum iron-binding protein, transferrin, and initially MTf was thought to play a role in iron uptake by these cells. However, a series of studies by the applicant demonstrated that MTf did not play a major role in iron uptake by melanoma cells (Richardson et al. 1990, 1991a,b). In fact, most iron taken up by t ....Melanotransferrin (MTf) is a membrane bound molecule that was originally identified in the malignant melanoma skin cancer and other tumours. Interestingly, MTf has many similarities to the serum iron-binding protein, transferrin, and initially MTf was thought to play a role in iron uptake by these cells. However, a series of studies by the applicant demonstrated that MTf did not play a major role in iron uptake by melanoma cells (Richardson et al. 1990, 1991a,b). In fact, most iron taken up by these cells was via the binding of transferrin to the transferrin receptor. More recently, under the current NHMRC grant, we have been able to confirm and signficantly extend our previous studies to convincingly show that MTf is not involved in iron uptake by melanoma cells where it is expressed at very high levels (Richardson 2000 Eur. J. Biochem. 267 (in press). In addition, we showed that the expression of MTf in 50 human tissues was very different to transferrin and the transferrin receptor (TfR) that are well known to be involved in iron transport. For example, the TfR is expressed at high levels in tissues that require large amounts of iron eg. the placenta and bone marrow. In contrast, MTf was not expressed at high levels in these tissues, but was found in large amounts in unexpected locations such as the salivary gland. Furthermore, the expression of MTf was widespread through a variety of tissues, and in contrast to expectations, was found at higher levels in normal rather than fetal tissues. It is also intesting that MTf is found in the blood and brain of Alzheimer's disease patients. Our results suggest that MTf may play other unexpected roles apart from iron uptake. The present proposal will assess the roles of MTf in cellular functioning. This information will be very important in understanding the function of MTf in cancer cells, Alzheimer's disease and also in other tissues (eg. the salivary gland) where it is expressed at very high levels.Read moreRead less
Sex Differences In The Mechanisms By Which Stress Inhibits The Secretion And Actions Of GnRH
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have differ ....It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have different effects on reproduction in males and females. In this project we aim to determine how stress impairs reproduction in males and females. A major effect of stress appears to be to inhibit the secretion of a substance produced by the brain that is necessary for the regulation of reproduction. This substance is called gonadotrophin releasing hormone (GnRH) and it acts on a small gland at the base of the brain to cause the release of hormones that are essential for reproduction in both males and females. It is also possible that stress may inhibit the actions of GnRH. Our research suggests that there may be differences between males and females in the extent to which stress inhibits the secretion of GnRH from the brain and its actions to cause the release of other reproductive hormones. In this project we will determine how stress acts in the brain to affect the secretion and actions of GnRH in males and females. Our research will make a major contribution to our knowledge of the way that stress inhibits reproduction in males and females. This information is essential in order to develop specific remedies to overcome reproductive disorders caused by stress and to improve reproductive health in both sexes.Read moreRead less
Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.
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