Neuroendocrine control of fertility

The specific aim of our research is to identify the signal transduction pathways and the neural, cellular and molecular mechanisms underlying the control of gonadotrophin releasing hormone (GnRH) and gonadotrophin secretion during naturally occurring temporal changes in fertility. To this end, we have developed two complementary research lines to investigate the regulation of GnRH neuronal networks within the hypothalamus, on one hand, and the paracrine interactions within the pituitary gland that modulate the response of gonadotroph cells to GnRH stimulation on the other. The link between these two research lines is the participation of prolactin, a hormone that, in addition to its role during lactation, has been shown to negatively participate in the inhibitory regulation of the reproductive axis.  In collaboration with Professor Dave Bates (University of Nottingham) we have recently unravelled key components of the circannual biological clock, which reside within the pituitary and allow the physiological adaptation of the individual to a changing environment.  We have employed in vivo and in vitro strategies in an integrated manner using four experimental animal models: rat, sheep, horse and rhesus monkey. In addition, hypophysial and neuronal cell lines are used for molecular studies. Overall, this inter-disciplinary, multi-animal-model, integrated strategy has allowed us to investigate the topic from its molecular basis to whole animal systems.

In addition to this main research line, two additional, unrelated projects have been developed with institutions within and outside the UK to assess: i) the neuroendocrine mechanisms underlying the effects of transmeridian flying on equine performance; and ii) meiotic segregation in equine hybrids.

Selected Publications

  • Hodson, D.J., Henderson, H.L., Townsend, J. and Tortonese, D.J.  2012.  Photoperiodic modulation of the suppressive actions of prolactin and dopamine on the pituitary gonadotropin responses to gonadotropin-releasing hormone in sheep.  Biol. Reprod. 86: 122, 1-9.
  • Tortonese, D.J., Preedy, D.F., Hesketh, S.A., Webb, H.N., Wilkinson, E.S., Allen, W.R., Fuller, C.F., Townsend, J. and Short, R.V. 2011. Experimental jetlag disrupts circadian clock genes but improves performance in racehorses after light-dependent rapid resetting of neuroendocrine systems and the rest-activity cycle. J. Neuroendocrinol. 23: 1263-1272.
  • Hodson, D.J., Townsend, J. and Tortonese, D.J. 2010. Characterization of the effects of prolactin in gonadotroph target cells. Biol. Reprod. 83: 1046-1055.
  • Henderson, H.L., Townsend, J. and Tortonese, D.J. 2008. Direct effects of prolactin and dopamine on the gonadotroph response to gonadotrophin-releasing hormone. J. Endocrinol. 197: 343-350.
  • Henderson, H.L., Hodson, D.J., Gregory, S.J., Townsend, J. and Tortonese, D.J. 2008. Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in photoperiodic species through a gonadotropin-independent mechanism. Biol. Reprod. 78: 370-377.
  • Gregory, S.J., Townsend, J., McNeilly, A.S. and Tortonese, D.J. 2004. Effects of prolactin on the luteinizing hormone response to gonadotropin-releasing hormone in primary pituitary cell cultures during the ovine annual reproductive cycle. Biol. Reprod. 70: 1299-1305 .
  • Townsend, J., Sneddon, C.L. and Tortonese, D.J. 2004. Gonadotroph heterogeneity, density and distribution, and gonadotroph-lactotroph associations in the pars distalis of the male equine pituitary gland. J. Neuroendocrinol. 16: 432-440.
  • Meeran, D., Urbanski, H.F., Gregory, S.J., Townsend, J. and Tortonese, D.J. 2003. Developmental changes in the gonadotroph population of the rhesus monkey pituitary gland. J. Clin. Endocrinol. Metab. 88: 2934-2942.
  • Cave, B.J., Wakerley, J.B., Luckman, S.M. and Tortonese, D.J. 2001. Hypothalamic targets for prolactin: Assessment of c-Fos induction in tyrosine hydroxylase- and proopiomelanocortin-containing neurones in the rat arcuate nucleus following acute central prolactin administration. Neuroendocrinology 74: 386-395.
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