Dr Jeremy Smith began his research career at The University of Western Australia, where he was awarded First Class Honours in 1998. He went on to complete his PhD – on the satiety hormone leptin and its role in reproduction– under the supervision of Professor Brendan Waddell and was awarded Distinction in 2004. In 2003, Dr Smith was awarded a NICHD U54 Cooperative Contraceptive Research Centers Fellowship (US) and began work as a post-doctoral researcher with Professor Robert Steiner at the University of Washington. Here, Jeremy worked extensively on kisspeptin, a novel neuropeptide, vital in the neuroendocrine control of GnRH secretion and reproductive function. In 2006, Dr Smith was awarded a NHMRC Biomedical (Peter Doherty) Fellowship and returned to Australia to work with Professor Iain Clarke at the Department of Physiology, Monash University. Jeremy has now returned to UWA to continue his work and is funded by the NHMRC, ARC and is a recipient of an ARC Future Fellowship.
Jeremy’s work represents an exciting new field of neuroendocrinology. The recent discovery of mice and humans lacking the receptor GPR54 and their infertile phenotype has sparked scientists to explore the actions of kisspeptin, the endogenous neuropeptide ligand for GPR54. Jeremy’s research hopes to provide significant advancement to our knowledge of kisspeptin and its critical role in stimulating GnRH release and fertilty.
The effect of kisspeptin on energy expenditure.
Recent data from our laboratory demonstrate no effect of central kisspeptin treatment on accumulative food intake. Despite this, kisspeptin results in the activation of NPY cells in the hypothalamus. Electrophysiological data also suggests kisspeptin regulates the activity of NPY, and also POMC neurons. Taken together, these data strongly suggest kisspeptin has effects on energy expenditure. Experiments will be conducted to measure the direct effect of kisspeptin and kisspeptin antagonist on energy expenditure. Calorimetry experiments in mice will also be conducted. Finally, if kisspeptin effects on NPY and/or POMC neurons were direct, kisspeptin receptor expression must be expressed in these neurons. Double label in situ hybridization experiments will be conducted to determine this. Results from these experiments will shed light on the known link between the reproductive system and metabolism and will, potentially, offer novel therapeutic alternatives for the treatment of obesity and related metabolic disorders.
Are the effects of stress on the reproductive system mediated by kisspeptin signalling?
It is well known that stress has an inhibitory effect on fertility. Increased plasma concentrations of cortisol (in response to stress) inhibit normal reproductive function by suppressing gonadotrophin secretion, but the mechanisms involved are largely unknown. This project aims to determine whether the neuropeptide kisspeptin plays a role in mediating the effects of stress on the reproductive system. The project will involve measurement of Kiss1 mRNA (the kisspeptin gene) in the brains of animals subjected to acute psychosocial stress. Furthermore, the response to kisspeptin treatment will also be determined in stressed animals. Techniques will include collection of blood samples with subsequent analysis by LH radio-immunoassay. Collection of brain tissues will also be performed for subsequent in situ hybridization and immunocytochemistry analysis.
The role of kisspeptin in the placenta.
In humans, kisspeptin secretion into the peripheral circulation increases dramatically (approximately ten thousand-fold) during pregnancy and declines precipitously at term, indicating a placental origin. Moreover, plasma kisspeptin is elevated in gestational trophoblastic neoplasia but Kiss1 mRNA expression is reduced in term pre-eclampsia placentas, indicating a role for kisspeptin as a physiological trophoblast invasion inhibitor. We aim to determine the expression of Kiss1 mRNA in the mouse placenta and examine the effect of gestational age and feto-placental growth restriction.
2014: Smith JT, Western Australian Department of Health Career Development Fellowship Near Miss Grant ($50,000)
2014: Martin GB, Smith JT, Lehman MN, ARC Discovery Project DP140102495 Brain regulation of reproduction: challenging the ‘KNDy’ hypothesis ($390,000 over 3 years)
2014: Smith JT, Western Australian Department of Health, Medical and Health Research Infrastructure Fund 2013 Rnd17 ($20,595)
2013: Smith JT, Western Australian Department of Health, Medical and Health Research Infrastructure Fund 2012 Rnd16 ($11,777)
2012: Smith JT, ARC Discovery Project DP120100521 The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing hormone (GnRH) release
2012: Clarke IJ, Smith JT, Parkington H, NHMRC Project Grant 1024346 Gonadotropin inhibitory hormone (GnIH); a negative regulator of reproduction
2011: Monash University, Researcher Accelerator (MRA) Program
2010: ARC Future Fellowship Scheme FT0990986 Masterminding reproduction: Kisspeptin and RFamide-related peptide
2010: NHMRC Achievement Awards for Career Development 606577 Kisspeptin and its receptor mastermind reproduction. This award was declined and the Future Fellowship accepted.
2010: NHMRC Project Grant 606538 Kisspeptin and its receptor mastermind reproduction