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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
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
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.
Regulation Of Growth Hormone Profile By Metabolic Balance: Neuronal, Neuroendocrinal And Molecular Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$413,257.00
Summary
Obesity is associated with a reduction in growth hormone secretion. As growth hormone maintains muscle mass at the expense of fat this may further promote the obese condition. This project will determine the physiological role of ghrelin, a hormone that signals hunger, in maintaining growth hormone secretion under normal, fasting and obese conditions. Clarification of the role of ghrelin in regulating growth hormone secretion may aid in the development of pharmacological agents to assist and mai ....Obesity is associated with a reduction in growth hormone secretion. As growth hormone maintains muscle mass at the expense of fat this may further promote the obese condition. This project will determine the physiological role of ghrelin, a hormone that signals hunger, in maintaining growth hormone secretion under normal, fasting and obese conditions. Clarification of the role of ghrelin in regulating growth hormone secretion may aid in the development of pharmacological agents to assist and maintain weight loss.Read moreRead less
Identifying The Pathological Mechanism Of Polyalanine Expansion Mutations In The X-linked Hypopituitarism Gene SOX3
Funder
National Health and Medical Research Council
Funding Amount
$402,846.00
Summary
Mental retardation (MR) is a debilitating disorder which affects 1-3% of the population. In many cases, MR results from changes (mutations) in genes which regulate the development of the brain before birth. We are studying families with an inherited form of MR termed X-linked Hypopituitarism (XH) in which only boys are affected. In addition to intellectual disability, boys with XH also have poor pituitary function resulting in short stature and slow metabolism. In severe cases, where the pituita ....Mental retardation (MR) is a debilitating disorder which affects 1-3% of the population. In many cases, MR results from changes (mutations) in genes which regulate the development of the brain before birth. We are studying families with an inherited form of MR termed X-linked Hypopituitarism (XH) in which only boys are affected. In addition to intellectual disability, boys with XH also have poor pituitary function resulting in short stature and slow metabolism. In severe cases, where the pituitary has failed to form completely, these babies are extremely ill and in some instances do not survive. We have previously shown that XH is due to an unusual change in the SOX3 gene in which the number of consecutive alanine residues is increased above a critical threshold (polyalanine expansion mutations). Similar mutations have recently been identified in several other genes that also cause severe birth defects. However, little is currently known about how polyalanine expansion mutations cause these disorders. The overall aim of this proposal is generate a mouse model for this disorder. Analysis of these mice will help us to answer many unresolved questions about this disorder including: How does the mutant protein cause this disorder? Which parts of the brain and pituitary are affected and how is their function altered? How does the mutant protein affect other genes and proteins in the cell? Ultimately, we hope that this mouse model will help us to develop new and improved therapies for XH and other disorders that are caused by alanine expansion mutations.Read moreRead less
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