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
Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human deve ....Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human development, with consequences for biological and social function and behaviour throughout the lifecourseRead moreRead less