Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.
Reducing The Burden Of Breast Cancer Through Precision Prevention, Targeted Treatment And Enhanced Survivorship
Funder
National Health and Medical Research Council
Funding Amount
$1,491,192.00
Summary
Breast cancer affects 1 in 8 Australian women. Of all the cancers, breast cancer results in the largest number of years of healthy life lost from death and illness. My research will reduce this unacceptable burden of breast cancer for women and their families. Spanning prevention, through treatment to survivorship, it will facilitate reduced breast cancer incidence, more effective treatments and enhanced understanding of the effects of new treatments on ovarian function and fertility.
The Role Of Primordial Follicle Activation In Premature Ovarian Failure
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, both the quality and quantity of their eggs decline and their chances of conceiving plummets. Premature ovarian failure (POF) is a disease of infertility, diagnosed in 3% of all women, defined by the early onset of menopause before age 40. Our poor understanding of the factors that regulate female egg supply remains a major limitation in treating POF. I will study key factors responsible for controlling egg number, with practical implications for POF diagnosis and treatment.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
SOFT And TEXT Premenopausal Randomised Adjuvant Endocrine Breast Cancer Trials.
Funder
National Health and Medical Research Council
Funding Amount
$722,380.00
Summary
SOFT and TEXT trials enrolled premenopausal women with hormone-sensitive early breast cancer to assess if post-operative hormone treatment that included ovarian function suppression plus tamoxifen, or an aromatase inhibitor exemestane, could improve outcomes. Initial results indicate fewer breast cancer recurrences with the treatment combination of ovarian suppression plus exemestane as compared with tamoxifen, and follow-up of women in these trials can show if overall survival can be improved.
Preserving Ovarian Function During Chemotherapy And Old Age
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Chemotherapy treatment and the natural ageing process leads to ovarian failure and infertility. For young cancer survivors, chemotherapy induced infertility is devastating, and like aged women, leads to hormonal changes that lead to osteoporosis, diabetes, obesity, and neurodegeneration. Here, a new class of molecules will be tested for their ability to prevent and reverse infertility folllowing chemotherapy treatment, and in old age. These findings will improve the healthy lifespan of women.
Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide, yet its origins remain unknown. Androgens are implicated in the development of PCOS, but the decisive, invasive studies needed to confirm and elucidate their roles are not feasible in women. Hence, using our innovative mouse models of androgen resistant female mice, this study will determine the role of androgens in PCOS aiming to better understand, and identify new treatments for this common female reproductive disorder.
Cognitive Effects Of Adding Ovarian Function Suppression To Adjuvant Hormonal Therapy In Premenopausal Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$301,431.00
Summary
There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thu ....There is mounting evidence that potentially curative treatment for breast cancer might, in some women, have an adverse effect on their subsequent cognitive function i.e. their memory and ability to think clearly. Thus it is important that when new treatments are being tested, the testing includes collecting information on the effect of the new treatment on a woman's cognitive function. There is currently an ongoing large international study examining whether suppressing ovarian function (and thus decreasing oestrogen levels) in women having treatment for breast cancer will improve their outcomes. However,it is known that oestrogen is important for normal cognitive functioning in premenopausal women so there is some concern that dropping the oestrogen levels in this way might cause impairment in cognitive function. In this sub-study we will compare the cognitive function of women having ovarian function suppression with those who do not, to determine if there are any differences. We will also examine how this might affect quality of life.Read moreRead less
Studies Of The Paracrine Role Of Inhibin A/activin A In Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enor ....This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enormous difference to women s health in the following areas: contraception, the possibility of development of new methods of contraception that block egg release without affecting the normal ovarian cycle endocrinology; fertility treatment, better methods of obtaining mature oocytes without subjecting women to high dose gonadotrophin treatment and the accompanying sequelae; improving knowledge of the factors that promote satisfactory oocyte maturation and embryo development so that with improved implantation rates, fewer embryos need be replaced to achieve a pregnancy.Read moreRead less