Robert McLachlan is an internationally recognised clinician-scientist in male reproductive health. His basic research examines the genetic & endocrine regulation of sperm production. His clinical studies span male fertility regulation, the use of assisted reproductive treatments, and the evidence-based use of androgen replacement. As Director of Andrology Australia, he has a leading national role in professional and community education, developing research capacity and male health advocacy.
Role Of Stem-progenitor Cells In Endometrial Regeneration And Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$437,720.00
Summary
We have discovered 2 types of adult stem cells in the lining of the uterus (endometrium) that are likely responsible for its ability to grow a new lining each month. This project aims to determine if endometrial stem cells are shed into the pelvic cavity during menstruation to cause endometriosis, a common, chronic disorder affecting 6-15% of women during their reproductive years and for which treatments are suboptimal. This knowledge may change how endometriosis will be treated in the future.
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
Reproductive health critically impacts a woman’s wellbeing, irrespective of her choice to have children. The ovary and its hormones govern physiological events regulating health at puberty, across the menstrual cycle, during the establishment and maintenance of pregnancy, and in parturition, lactation and menopause. The major health burdens concerning ovaries that we are studying include polycystic ovarian syndrome and assisted reproductive technologies used to treat infertility.
Polycystic ovary syndrome (PCOS) affects a striking 9-21% of women of reproductive age. PCOS is an important health problem and can affect menstrual cycles, fertility and increase risk of diabetes and mood disorders. There is a lack of longitudinal studies that women with PCOS over time to examine the key determinants of PCOS, long-term impact of obesity and factors contributing to PCOS complications.
This research deals with the interaction between the reproductive system and the immune system, providing a unique perspective on two biological systems that are normally considered separately. This research may help to improve the treatment of infertility, reproductive tract infections and testicular cancer, but may also lead to new treatments for inflammatory diseases that hospitalise or kill many thousands of patients each year, and for preventing graft failure in transplant recipients.
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.
This fellowship will support a clinical researcher whose focus is improving metabolic and reproductive health by manipulating hormones and improving sleep. This will be achieved from a platform of NHMRC project grants and a NHMRC CCRE in interdisciplinary sleep health.
The Role Of Gonadotropins In Regulating The Production Of Alzheimer's Beta Amyloid
Funder
National Health and Medical Research Council
Funding Amount
$400,278.00
Summary
Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause ....Currently, about 160,000 Australians suffer from dementia; of which 50-70% are Alzheimer's disease (AD) cases. AD is characterised clinically by memory and personality changes and pathologically by deposition of amyloid. Of particular importance in the disease pathogenesis, is a small molecule called beta amyloid, of which the overproduction is thought to be central to the development of AD. Changes in the levels of the reproductive hormones, particularly low levels of oestrogen during menopause or testosterone during andropuase, has been associated with the increased risk of developing AD and in altering the levels of beta amyloid. Furthermore, menopause and andropause are also characterised by changes in other reproductive hormones such as the gonadotropins. High levels of the gonadotropins have also been associated with the increased risk of developing AD. Therefore it is important to identify how these changes modify the risk of developing AD. This study examines the role of the gonadotropins in regulating beta amyloid levels in cell culture and in an animal model for AD. Furthermore, this study will assess, in the animal model, the use of gonadotropin lowering agents to reduce levels of beta amyloid. The results from this study will provide important data on how reproductive hormones regulate beta amyloid. Further insight into these mechanisms will provide therapeutic or preventative strategies for AD.Read moreRead less