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This project is about the way that the brain controls reproduction. It is important because there is no known cause for infertility in a significant number people with such a problem. The project should inform us on new ways to manage particular forms of reproductive failure.
Gonadotropin Inhibitory Hormone (GnIH); A Negative Regulator Of Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$752,936.00
Summary
Gonadotropin inhibitory hormone (GnIH) is a short peptide of 8 amino acids that is produced by the brain and acts in a negative manner on brain and pituitary cells that control reproduction. This project aims to elucidate the role of GnIH in normal physiology and in states of stress and negative metabolic state. Work will be carried out in various species to define the function of the peptide and also to investigate ways that it can be utilised to prevent reproduction.
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
Pathways For Estrogen Feedback To Gonadotropin Releasing Hormone Neurons
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Gonadotropin releasing hormone (GnRH) is the brain hormone that drives the reproductive process. In the female, a surge in the secretion of GnRH is the trigger for ovulation. An understanding of the mechanisms that regulate the secretion of GnRH is, therefore, extremely important if we are to decipher abnormalities that lead to infertility. Understanding of the ovulatory process is also important for the development of new (possibly simpler) means of contraception. Our research is intended to pr ....Gonadotropin releasing hormone (GnRH) is the brain hormone that drives the reproductive process. In the female, a surge in the secretion of GnRH is the trigger for ovulation. An understanding of the mechanisms that regulate the secretion of GnRH is, therefore, extremely important if we are to decipher abnormalities that lead to infertility. Understanding of the ovulatory process is also important for the development of new (possibly simpler) means of contraception. Our research is intended to provide a full understanding of the brain circuits that provide input to the GnRH neurons. In particular, we will focus on the microcircuitry in the preoptic area, where GnRH cells are found. In addition to providing a full understanding of the circuits that are primarily involved in regulating GnRH secretion, this work will provide a substrate upon which we can expand knowledge of how factors such as emotion and stress can impact on the reproductive process.Read moreRead less
Neuroendocrine Mechanisms By Which Leptin Regulates Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not k ....The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not known. Leptin is a hormone that is produced by fat and acts on the brain. This appears to be one of the means by which the reproductive system is regulated. Leptin also regulates food intake and other brain processes. Leptin acts on specific cell types in the brain. Some of these may have dual function to regulated appetite as well as reproduction. The present proposal is for work to determine mechanisms within the brain that are altered by leptin. We will also determine which specific mechanisms relate to the regulation of gonadotropin releasing hormone. The work will provide information on how putative appetite regulators might affect the reproductive axis. Such work will provide a platform for design of pharmaceutical means to manipulate the reproductive axis and will impact on the design of drugs that regulate obesity. It is possible that drugs that developed to control obesity may affect the reproductive axis and the project will identify these.Read moreRead less
Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance ....Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance of kisspeptin and the relevant receptor, GPR54, is not well defined. This project aims to use our unique combination of abilities to determine the significance of kisspeptin in the regulation of GnRH and gonadotropin secretion. We will study both sheep and monkey brains, measuring gene expression for kisspeptin and GPR54 in a range of physiological states and we will determine how kisspeptin acts on GnRH cells. We will determine whether kisspeptin plays a role in the feedback effects to GnRH cells. Effects on the pituitary gland will also be studied. We will use sheep models to measure kisspeptin effects on GnRH secretion, because this cannot be done in the monkey or the rodent. We will examine the function of kisspeptin and GPR54 in relation to puberty. We will also use a model of puberty (seasonal breeding in the sheep) to determine whether activation and quiescence of the reproductive system is related to the function of kisspeptin and GPR54. This work will define the role of kisspeptin in the regulation of reproduction.Read moreRead less
Phase Shifting Endocrine And Sleep/activity Rhythms With Light And Serotonergic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$561,430.00
Summary
All biological systems, including those of humans, are influenced by changes in the environment, especially by variations in the amount of daylight. In animals the external rhythm of light and darkness interacts with a small part of the brain called the suprachiasmatic nucleus (SCN-often called the biological clock) which has its own self sustained rhythms. The SCN in turn orchestrates rhythms in the secretion of the hormone melatonin from the pineal gland, body temperature, the timing of sleep ....All biological systems, including those of humans, are influenced by changes in the environment, especially by variations in the amount of daylight. In animals the external rhythm of light and darkness interacts with a small part of the brain called the suprachiasmatic nucleus (SCN-often called the biological clock) which has its own self sustained rhythms. The SCN in turn orchestrates rhythms in the secretion of the hormone melatonin from the pineal gland, body temperature, the timing of sleep and the secretion of other hormones. The aim of this study is to extend our knowledge of the inter-relationships between light, the chemical messengers that nerves use to communicate with each other, the biological clock and rhythms in body functions. We will concentrate on one particular chemical messenger called serotonin which we believe plays an important role in keeping rhythms in synchrony with the natural day-night cycle. The results are expected to be of benefit in understanding how certain sleep timing disorders arise and provide some insight into how they might be treated.Read moreRead less
I am a perinatal physiologist who specializes in determining the factors that cause fetal and neonatal brain damage, and in devising treatments to prevent this for application in pregnant women and the neonate.
Investigating The Synergistic Role Of Brain-derived Neurotrophic Factor (BDNF) And Estradiol On Parvalbumin-mediated Cognitive Function: Relevance To Dementia
Funder
National Health and Medical Research Council
Funding Amount
$589,644.00
Summary
Estrogen-based therapy may improve cognitive functioning in dementia patients. However, more detailed knowledge is required to ensure safe and effective targeted treatment is provided. I propose to examine, in mouse models, the mechanistic functioning of estrogen signalling in key brain regions involved in cognition. Unravelling the way estrogen impart its beneficial effect can lead to the development of effective treatments for dementia and many other devastating neurological diseases.