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
Kisspeptin And Its Receptor Mastermind Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Reproduction is controlled by the brain and gonadotropin releasing hormone (GnRH) is the primary stimulatory factor. Finding critical regulators of GnRH has remained the most important goal for reproductive endocrinologists for over 30 years. The brain peptide hormone called kisspeptin and its receptor Kiss1R appear vital in the control of reproduction. This project will detail the role kisspeptin and Kiss1R play in controlling hormones from the brain that govern puberty and reproduction.
Novel Interactions Between GnRH Receptor And E2F4 Transcription Factor.
Funder
National Health and Medical Research Council
Funding Amount
$462,750.00
Summary
The reproductive endocrine system is under the control of gonadotropin-releasing hormone (GnRH), signalling via its G-protein coupled receptor (GPCR) in the anterior pituitary gland. The GnRH receptor (GnRHR) is the drug target for the treatment of a range of endocrine-related disorders as well as hormone-dependent cancers. Sustained treatment with either GnRH agonists or antagonists can block gonadotropin secretion indirectly, via down-regulation of the pituitary receptor resulting in a reducti ....The reproductive endocrine system is under the control of gonadotropin-releasing hormone (GnRH), signalling via its G-protein coupled receptor (GPCR) in the anterior pituitary gland. The GnRH receptor (GnRHR) is the drug target for the treatment of a range of endocrine-related disorders as well as hormone-dependent cancers. Sustained treatment with either GnRH agonists or antagonists can block gonadotropin secretion indirectly, via down-regulation of the pituitary receptor resulting in a reduction of gonadotropin secretion and consequent decline in steroid production. As the majority of tumours treated with GnRH analogues are hormone-dependent, this starves the tumour of the steroid support required for growth. However, the concept of a direct anti-tumour effect of GnRH, independent of the pituitary-gonadal axis, is supported by the in vitro inhibition of both cell growth and DNA synthesis in a number of tumour cell lines. Despite the wide use of GnRH analogues, the molecular basis of the growth inhibitory effects resulting from the activation of this receptor is not fully understood. Unravelling the protein interactions underlying receptor-mediated signalling events will provide valuable information towards understanding of receptor function in vivo. We have identified a novel interaction involving the GnRHR and E2F4, a transcription factor involved in suppression of the transcription of genes involved in cell cycle progression. In addition, over 80% of E2F4 knockout mice are sterile. Owing to the role of the GnRHR in the reproductive pathway we are interested in determining whether the GnRHR-E2F4 interaction has an influence on the development of the hypothalamic-pituitary-gonadal axis, hence affecting reproductive capacity. The interaction identified and studied in this proposal has implications for the treatment of reproductive tumours, such as those of the breast and prostate, and understanding the development of the hypothalamic-pituitary-gonadal axis.Read moreRead less
Targeting The Gonadotropin-releasing Signal Transduction Cascade Novel Approaches To Regulating Reproduction And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$438,625.00
Summary
We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close ....We know that nutrition and reproduction are closely linked e.g. undernutrition leads to infertility, menopause to weight gain, but we do not know precisely the mechanisms whereby these events occur. The brain hormone gonadotropin-releasing hormone (GnRH), which stimulates the reproductive pathways and a recently discovered family of hormones (orexins) which stimulate feeding both act through the same type of recognition site i.e. G-protein coupled receptors (GPCRs) which are distributed in close proximity within the brain. Identifying how these two pathways interact has enormous potential for the treatment of disorders of weight and-or reproduction since the GPCR structure and the route by which it signals lends itself to therapeutic intervention.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