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
ELF5 Integrates Prolactin And Progestin Control Of Mammary Gland Development Via Regulation Of Progenitor Cells.
Funder
National Health and Medical Research Council
Funding Amount
$720,515.00
Summary
Elf5 may act as a master-regulator of mammary cell growth during pregnancy. We will demonstrate that Elf5 can replace the requirement for prolactin and progesterone to trigger mammary development and we will determine the stem or progenitor cells Elf5 acts on. Finally we will apply this knowledge to breast cancer cell lines to discover what role Elf5 plays in breast cancer. These experiments have the potential to establish Elf5 as a new therapeutic target for the treatment of breast cancer.
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
Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
Significance And Mechanisms Of Relative Progesterone Receptor Isoform Expression In Normal And Malignant Target Tissues
Funder
National Health and Medical Research Council
Funding Amount
$737,248.00
Summary
The ovarian hormone progesterone has a pivotal role in normal female physiology, in the uterus and ovary; in the mammary gland and in the brain. Human progesterone receptor, through which progesterone exerts its physiological effects, is expressed as two receptor proteins (PRB and PRA). These are identical except that PRA is shorter than PRB and present knowledge supports a role for both proteins in normal physiology. PR is also expressed in breast cancers, where one of its roles may be to inhib ....The ovarian hormone progesterone has a pivotal role in normal female physiology, in the uterus and ovary; in the mammary gland and in the brain. Human progesterone receptor, through which progesterone exerts its physiological effects, is expressed as two receptor proteins (PRB and PRA). These are identical except that PRA is shorter than PRB and present knowledge supports a role for both proteins in normal physiology. PR is also expressed in breast cancers, where one of its roles may be to inhibit oestrogen action and thereby limit tumour growth. A tumour which lacks PR would lack this capacity and this may be clinically associated with poorer prognosis. We have shown that primary tumours lacking PR are more likely to progress to secondary sites and this may provide support for this possibility. In addition, we have shown that over-expression of one PR isoform in breast cancers can be as biologically significant as lack of PR: tumours expressing predominantly one isoform were associated with poorer prognosis features.This project is aimed at investigating how PRA and PRB exert their effects on the range of progesterone targets in normal and malignant tissues. We will do this by determining whether PR isoforms are located in the same nuclear site in cells expressing one versus cells expressing both PR isoforms, to explore whether the proteins act separately in target cells. We will then ask whether the PR activity is different if only one isoform (PRA or PRB) is expressed versus both PRA and PRB. Another major issue which will be explored is the way in which the relative levels of PRA and PRB are controlled, and whether this is altered in breast cancers. Finally, we will explore the clinical significance of PR isoform expression. If achieved, the aims of this project will delineate the individual and combined action of - THIS FIELD WAS OVER 2000 CHARS, TEXT WAS REMOVED TO LODGE THE APPLICATION. A COPY OF THE ORIGINAL APPLICATION IS AVAILABLE FROM ARCHIVE-HARDCOPYRead moreRead less