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.
Australia has an ageing population and women spend around one third of their lives after menopause. Optimising physical and emotional health at menopause is a national health priority, and improving the health of women will improve health for the community. This research program is targeted at improving physical and mental health for midlife and older women. Findings will be translated into changes in policy and practice which improve the lives of women in Australia and worldwide
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.
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
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.
Investigating Role Of Insulin Resistance And Sympathetic Nervous System In Metabolic Features Of PCOS
Funder
National Health and Medical Research Council
Funding Amount
$150,468.00
Summary
PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences assoc ....PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences associated with PCOS.Read moreRead less
The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing hormone (GnRH) release. The brain controls fertility through the secretion of its primary stimulatory factor, gonadotropin releasing hormone (GnRH). Brain cells producing three key peptide hormones, kisspeptin, neurokin B and dynorphin (termed KNDy cells) are vital for the control of GnRH. This project will detail the role of KNDy cells in puberty and reproduction.
Size matters, but at what cost? Role of male sex hormones in the placenta. This project aims to understand molecular pathways regulated by male sex hormones in the placenta that may contribute to sex-specific fetal growth and survival outcomes in response to reduced oxygen and/or glucose. Through this project, we expect to generate new knowledge of the mechanisms that drive sex-specific placental molecular function using interdisciplinary approaches. The application of this advanced understandin ....Size matters, but at what cost? Role of male sex hormones in the placenta. This project aims to understand molecular pathways regulated by male sex hormones in the placenta that may contribute to sex-specific fetal growth and survival outcomes in response to reduced oxygen and/or glucose. Through this project, we expect to generate new knowledge of the mechanisms that drive sex-specific placental molecular function using interdisciplinary approaches. The application of this advanced understanding of the sex-specific regulation of placental molecular function and fetal growth may be targeted in future studies to improve fetal growth outcomes in placental mammals such as livestock, domestic pets, and humans.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less
Brain Regulation of Reproduction: Challenging the ‘KNDy’ Hypothesis. The brain switches reproduction on and off by changing the frequency of pulses of gonadotrophin releasing hormone. The processes that produce the pulses have been a puzzle for decades but, recently, brain cells that produce three peptides (kisspeptin, neurokinin B, dynorphin), known as ‘KNDy cells’, have been heralded as the ‘missing link’, or even the ‘pulse generator’. Using sheep, this project will challenge the KNDy hypothe ....Brain Regulation of Reproduction: Challenging the ‘KNDy’ Hypothesis. The brain switches reproduction on and off by changing the frequency of pulses of gonadotrophin releasing hormone. The processes that produce the pulses have been a puzzle for decades but, recently, brain cells that produce three peptides (kisspeptin, neurokinin B, dynorphin), known as ‘KNDy cells’, have been heralded as the ‘missing link’, or even the ‘pulse generator’. Using sheep, this project will challenge the KNDy hypothesis with pheromones and with acute increases in nutrition, two factors that rapidly increase the frequency of gonadotrophin releasing hormone pulses. The outcomes of this research are directly relevant to the optimisation of reproductive management in farm animals, wildlife and humans.Read moreRead less