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
Age-Related Changes In Body Composition And Fuel Metabolism: The Role Of Glucocorticoid Signalling In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$820,528.00
Summary
Our previous studies suggest that age related changes in fat tissue could be due to an increased level of glucocorticoids within bone forming cells (osteoblasts). Mice in which the level of glucocorticoids in osteoblasts is selectively decreased were no different from normal mice at a young age but with ageing were protected against development of obesity and diabetes. This project will examine how bone influences age related changes in fat mass and examine ways in which this might be prevented.
Transcriptome Landscape Of Brown/beige Adipogenesis In Humans
Funder
National Health and Medical Research Council
Funding Amount
$393,369.00
Summary
There are three kinds of fat in the body: white, brown and beige. While excess white fat results in obesity, brown fat is associated with leanness and lowers blood glucose levels. Recent animal experiments show that under certain conditions, white fat can be transformed into beige fat, leading to benefits such as weight loss. The current project grant involves examination of human fat cells grown in the laboratory and investigation on the genetics of brown and beige fat.
The nuclear hormone receptors (NRs) translate hormonal, metabolic & pathophysiological signals into gene regulation, and several NRs are very important in human health. NRs are important therapeutics targets in the treatment of dyslipidemia, insulin insensitivity and breast cancer. Our data identifies new and novel NR targets that can be therapeutically/pharmacologically exploited in the context of exercise capacity, metabolic disease and breast cancer.
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvasc ....Blood flow routes in muscle. Ageing well, ageing productively. The Australian population is ageing. The proportion of the population over the age of 65 is expected to greatly increase, reaching 22% by the year 2030. The prevalence of type 2 diabetes in this older population is thought to be ~20%, compared to ~6% in younger populations. An initial cause of type 2 diabetes may be microvascular dysfunction brought on by physical inactivity. Therefore this project addresses the concepts of microvascular function and microvascular fitness by using the latest technology to map blood flow routes in muscle under a number of relevant situations. Read moreRead less
Microdialysis for monitoring changes in microvascular flow patterns in muscle. Microdialysis is a technique for sampling interstitial fluid. Factors altering vascular delivery and removal of nutrients and hormones can affect muscle metabolism by altering exchange with the interstitium. This project focuses on microdialysis for assessing the impact of microvascular blood flow patterns on skeletal muscle metabolism and contractility. The aim is to develop and refine the technology, including equat ....Microdialysis for monitoring changes in microvascular flow patterns in muscle. Microdialysis is a technique for sampling interstitial fluid. Factors altering vascular delivery and removal of nutrients and hormones can affect muscle metabolism by altering exchange with the interstitium. This project focuses on microdialysis for assessing the impact of microvascular blood flow patterns on skeletal muscle metabolism and contractility. The aim is to develop and refine the technology, including equations, specifically for monitoring the nutritive fraction of blood flow in muscle by agents and factors relating to health and disease. This technique could be used for screening drugs in the treatment of diseases such as type 2 diabetes and related conditions.Read moreRead less
Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precociou ....Masterminding Reproduction: Kisspeptin and RFamide-Related Peptide. There are a number of concerning trends in reproductive health. Women are reporting difficulty conceiving and maintaining pregnancies; while sperm count and quality are declining in men. More concerning is the increase in reproductive cancers. Gonadotropin-releasing hormone (GnRH) antagonist and agonist have been used for decades to treat reproductive cancers (such as breast cancer and prostate cancer), infertility and precocious puberty. Kisspeptin and RF-related peptide may offer more physiological alternatives to GnRH, without detrimental side effects. We will fully explore these two newly defined and major players in reproduction and provide a physiological framework for their progression to clinical use.Read moreRead less