Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
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.
Progesterone Receptor-mediated Coordination Of Oocyte-oviduct Communication During Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$86,128.00
Summary
Infertility affects 1 in 6 couples, often due to failed release of an egg from the ovary. The hormone progesterone is essential for this process. Our goal is to determine how progesterone signals the egg to ensure its correct release into the oviduct where fertilization may occur. To identify these signals, experiments will analyse ovary cells and eggs of mice, including mice that do not respond to progesterone. The results will provide much needed information about female reproductive health.
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.
Hormonal Control Of Serotli Cell Maturation And Function
Funder
National Health and Medical Research Council
Funding Amount
$512,898.00
Summary
This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR ac ....This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR activity within Sertoli cells is essential for 'induction' of complete sperm development. Ongoing work will develop unique 'inducible' transgenic models that will allow, for the first time, selective analysis of Sertoli AR in both 'developing' and 'adult' testes. Our innovative models will allow AR function to be switched on or off at any stage of development, providing unique opportunity to determine the key AR-regulated factors and pathways controlling induction, maintenance or restoration of sperm production. In past NHMRC research we created a novel transgenic model to study another major reproductive hormone, FSH. Using the hormone-deficient background of 'hpg' mice, we found that androgen and FSH act synergistically in the developing 'meiotic' germ cells that form sperm. Using the latest microarray gene technology we generated datasets of androgen-regulated genes with or without FSH activity, which combined with our unique transgenic AR and FSH models, will be used to identify key pathways, including those enhanced by androgen-FSH synergism, in the early testicular response. Our research will provide new knowledge of the precise roles and pathways of testicular AR actions, to ultimately identify key genetic and regulatory factors as targets for significantly improved therapy for male infertility, gonadal tumours, or contraception.Read moreRead less