Centre for Neuroendocrinology (CNE)

The detection and integration of diverse exogenous environmental inputs (eg light, temperature, stress, visuals, nutrients, toxins, odorants, pheromones and pathogens) and endogenous signals (eg hormones, growth factors, inflammatory and stress mediators, neurotransmitters, metabolites, ions, water and electrolytes and lipids) in the vertebrate brain is crucial for homeostasis and survival.  The hypothalamic region at the base of the brain integrates these diverse inputs via the secretion of neuropeptides which are released into a portal system to target the anterior pituitary which regulates reproduction, adrenal function, thyroid function, appetite, metabolism and growth.  Hypothalamic neuropeptides are also secreted into the general circulation to target end organs such as the kidney (water and electrolyte regulation), uterus (parturition) and breast (lactation).  The field Neuroendocrinology has therefore yielded important insights into normal and deranged homeostasis in vertebrates and produced a range of billion dollar therapeutics which are widely used in man, companion animals and livestock.  Indeed it is fair to say that there are no area of biomedical physiology and pathophysiology that are not impacted by Neuroendocrinology, and some of these, such as obesity, metabolic syndrome and diabetes, are now global pandemics with vast implications for ill health.  Despite its impact Neuroendocrinology is insufficiently researched in Africa and the Centre for Endocrinology – spanning the full specrum of atomic level structural and melocular biology, cell biology and physiology – proposes to fill this gap through drug development to clinical research.


For more information regarding this institute, kindly visit the CNE home page

 


 

 

Research focus

Neuroendocrinology: Brain Body Dialogues

SDGs of focus

 

Relevance and importance to UP, South Africa and Africa

The detection and integration of diverse exogenous environmental inputs (e.g. light, temperature, stress, visual stimuli, nutrients, toxins, odorants, pheromones and pathogens) and endogenous signals (e.g. hormones, growth factors, inflammatory and stress mediators, neurotransmitters, metabolites, ions, water and electrolytes and lipids) in the brain is crucial for health and survival. To this end the Centre for Neuroendocrine Research, has been established to create a new compendium of expertise and knowledge acquisition in the extensive and diverse terrain relevant to animal production, human health and wildlife conservation. This field provides new diagnostics and therapeutic interventions.  While this new Centre is headed by an A-rated researcher, Professor Robert Millar, he is complemented by three excellent young up and coming researchers who are well positioned to grow this theme in the future.

The potential benefit to science and to society

The field, Neuroendocrinology, yielded important insights into normal and deranged homeostasis and has produced a range of billion dollar therapeutics which are widely used in man, companion animals and livestock. Indeed it is fair to say that there is no area of biomedical physiology and pathophysiology that are not impacted by Neuroendocrinology, and some of these, such as obesity, metabolic syndrome and diabetes are now global pandemics with vast implications for ill health. Despite its impact, Neuroendocrinology is not well researched in South Africa and therefore the establishment of the “Centre for Neuroendocrinology: Brain/Body Dialogues” at UP is of national value and importance.

Translational clinical studies will be conducted in Sports Science and Medicine. Examples are the effects of kisspeptin agonists on infertile patients on widely employed antipsychotic therapy, the application of patented kisspeptin and neurokinin B antagonists to slow LH pulses in the vexing disease of Polycystic Ovarian Syndrome and hot flushes and the development of a novel patented GnRH analogue for prostatic cancer treatment. The support of Pharmacology, commercial partners and the Tecnology Innovation Agency (substantial funding) has been harnessed for clinical proof-of–concept studies.

The centre’s latest research is a novel discovery of treating patients with inactivating mutations in genes of G-protein coupled receptors which comprise 80% of all receptors regulating normal function and are therefore responsible for much ill health such as blindness, diabetes, obesity, reproductive, adrenal, and thyroid function as well as water, salt and calcium balance. The centre has discovered small molecules which can specifically restore function to the mutant receptors and is already testing one of these clinically.

Clinical veterinary studies will target interrogation of stress pathways in dogs and increasing reproductive capacity as well as contraception of livestock and companion animals as an alternative to invasive castration. An additional partner is NECSA who currently commercially produce radionuclide somatostatin analogue for Neuroendocrine cancer detection and therapy. We have proposed radionuclide labelling of novel neuroendocrine peptides by NECSA which have promise as novel diagnostics and therapeutics for neuroendocrine tumours, especially as combined therapeutics. These molecules will be investigated in animal and human studies with scanning equipment in Nuclear medicine.

Benefits to investing in this research area

This research team, under Prof Millar’s lead is cognisant of the importance of ongoing scientific research to improve lives all over the continent and in the training of young African scientists. The team will continue to look for new and more effective treatments for diseases which lead to considerable suffering.

Investment in this area will contribute to the research development which resonates with the South African thematic areas:

  1. A long and healthy life for all South Africans through neuroendocrine research on obesity and diabetes (entering pandemic proportions), women’s health (endometriosis, fibroids, PCOS, infertility, alternative contraception, hot flushes) and on breast, ovarian and prostatic cancers.
  2. Food security through contributions in animal production via utilization of novel neuropeptides to stimulate the reproductive axis for animal breeding programmes.
  3. The Centre for Neuroendocrinology seeks to develop analogues of neuropeptides regulating reproductive and stress pathways, and identifying novel neuropeptides for animal and “first in man” studies.
  4. This also reports to the Health Innovation theme and particularly Chronic Disease through use of neuroendocrine analogues to treat women’s health conditions (see above), cancer therapy and metabolic disease (e.g. obesity) articulated earlier.
  5. The proposed research reports to the Drug Discovery theme as the research has the credible aims to discover novel neuroendocrine molecules and provide the full drug development continuum to refine them and take them into the clinic. The Centre has already taken several neuroendocrine analogues into humans.
  6. The research also addresses the theme of Climate Change and Biodiversity as the neuroendocrine system is a recognized sensitive biomarker of temperature and stress through the hypothalamic-pituitary-gonadal axis, the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-thyroid axis.  Monitoring these cascades and provocative testing in indicator species with central and peripheral hormones has the possibility of providing a new “early-warning” index in this important arena which has not been previously exploited.
  7. The importance and accomplishments in the field has been recognised by recent awards to Professor Millar of the Medical Research Council’s Plantinum award, the African Union’s Kwame Nkruma continental award for scientific excellence, the John Herschel award of the Royal Society (highest ward) and the Harry Oppenheimer award amongst others.
Published by Nicola Vernall

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