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
Orexins As Neuroendocrine Integrators Between Nutrition And Reproduction Control Systems
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Studies on humans and a range of animal species have shown that the effects of nutrition on reproduction are mediated at least partly by changes in the secretion of gonadotrophin releasing hormone (GnRH) and thus gonadotrophins. A number of metabolic signals must also be involved but those tested to date (glucose, insulin, leptin) do not seem to play major roles. Two exciting new candidates are orexin-A and orexin-B, a recently discovered pair of peptides that stimulate feeding behaviour. They a ....Studies on humans and a range of animal species have shown that the effects of nutrition on reproduction are mediated at least partly by changes in the secretion of gonadotrophin releasing hormone (GnRH) and thus gonadotrophins. A number of metabolic signals must also be involved but those tested to date (glucose, insulin, leptin) do not seem to play major roles. Two exciting new candidates are orexin-A and orexin-B, a recently discovered pair of peptides that stimulate feeding behaviour. They are synthesized in the brain and, in rodents, they either stimulate or inhibit gonadotrophin secretion, depending on the presence of sex steroids. In this project, we will investigate the roles of the orexins as integrators of signals about gonadal activity, nutrition and body condition, all of which affect the activity of the reproductive control centres in the brain. We will use the mature male sheep because it shows clear and repeatable reproductive responses to changes in nutrition. We will locate the orexin-producing cells and the cells that respond to the orexins, and show how orexin production is affected by diet. We will also study the ways in which the orexins affect, and are affected by, the hormone systems that control reproduction and metabolism. Finally, we will try to find out why there are two orexins by looking at how their actions differ. Ultimately, the orexin system might explain the brain processes that are behind many of the reproductive problems that are associated with metabolic disorders, such as appetite loss, excessive exercise, undernutrition, polycystic ovarian syndrome, and insulin-dependent diabetes.Read moreRead less
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
Development Of Novel Medical Therapies To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$601,156.00
Summary
Ectopic pregnancies are conceptions implanting outside the womb, mainly the fallopian tube. They are pathological, and can erode straight through the tube into large blood vessels causing fatal bleeding and death. We plan to assess three medication based approaches to treat this condition that would avoid surgery entirely. If we succeed, and subsequently translate one or more of these treatments to the clinic, it would revolutionise management of this serious gynaecological emergency.
A New Model Of Asthenospermia And A Candidate Gene For Multiple Ciliopathies
Funder
National Health and Medical Research Council
Funding Amount
$629,039.00
Summary
Though the analysis of a unique mouse strain (Mot1) we have identified a previously unknown cause of male infertility and lung disease. We hypothesis that the Mot1 line is a model of human primary cilia dyskinesia and that the Mot1 protein is involved in cilia function. Within this project we will define the consequences of a loss of Mot1 protein function, we will define its binding partners and we will screen for mutations in the corresponding human gene.
I am an immunologist with a background in virology and peptide chemistry and my work is therefore inter-disciplinary but focused on the design of synthetic, epitope-based vaccines against infectious agents particularly influenza and hepatitis C viruses an
Effects Of Leptin On Follicle Growth And Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$196,470.00
Summary
Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and pr ....Leptin is a recently discovered hormone which is very important in controlling body weight. Extremely obese, or extremely underweight women, find it difficult to become pregnant, and leptin is probably the connection between weight and fertility. This may be a particularly important factor in polycystic ovary syndrome (PCOS), a distressing condition which affects 5% of women and causes both obesity and infertility. Exciting new research suggests that leptin also affects the immune system, and previous NH and MRC funding has enabled us to demonstrate that the immune system plays a crucial role in maintaining normal ovarian function. The nutritional status of the body, the immune system and the reproductive system all interact, and leptin appears to be the connecting link between these three major systems. We propose that leptin plays a major role in the ovary, and wish to determine how leptin mediates the effects of bodyweight and the immune system on ovarian function. Laboratory rats will be treated with leptin, their food intake and weight recorded, and a few weeks later the rats will have their ovaries removed. We will find out whether ovaries respond to leptin, or whether the ovarian response changes according to the menstrual cycle: perhaps leptin is very important just before ovulation, but it does not affect menstruation? Do any ovarian cells make leptin? Will leptin stimulate ovaries to produce more oestrogen or progesterone, or ovulate more eggs? We will also identify immune system cells in the ovary, and note whether leptin affects them. We will be able to relate all this data to weight and diet. Increased understanding of leptins' effect on the ovary has the potential to lead to new, improved treatments for PCOS or for unexplained cases of infertility. It is also possible that in the future a weight-loss regime might be developed which takes a womans monthly cycle into account, therefore making weight-loss more efficient and attainable.Read moreRead less
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less