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Stephen Matthews
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Faculty Profile

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Stephen G. Matthews

Contact Information:
Mailing Address:
Department of Physiology
Faculty of Medicine
University of Toronto
1 King’s College Circle
Toronto, ON M5S 1A8
Phone Number: 416-978-1974
Fax Number: 416-978-4940
Email Address:  stephen.matthews@utoronto.ca

Degrees & Professional Designations:
  • BSc Hons: Animal Physiology
  • University of Nottingham, UK (1988)
  • PhD: Molecular Neuroendocrinology
  • University of Cambridge, UK (1992)

Academic Position: Professor

Primary Appointment: Department of Physiology

Cross Appointments:
Department of Medicine
Department of Obstetrics and Gynaecology

Hospital Affiliation/Practice Location: n/a

Key Interests:
Research: Regulation and plasticity of neuroendocrine systems during development.

Current Research Grants and Projects:
Source Title /annum(total) Term
CIHR Multidrug resistance in pregnancy
Operating Award. Principal-Investigator
$127,596 ($637,980) Oct05-10
CIHR Fetal glucocorticoid exposure modifies hypothalamo
Pituitary-adrenal function throughout life: Mechanisms of programming. Operating Award. Principal-Investigator
$101,732 ($508,660) Oct01-06
 CIHR Maternal Adversity, Vulnerability & Neurodevelopment
Program Grant, Co-Director with M. Meaney (Montreal)
$750,000 ($3,750,000) Aug03-09
NSERC Maternal stress programs adrenal function and behaviour in adult offspring. Operating Award. Principal-Investigator $42,100 ($168,400) Apr01-06
CIHR Control of Parturition
Operating Award. Co-Investigator (PI; J. Challis)
$210,000 ($1,050,000) Oct04-09
CIHR Fetal alcohol syndrome: oxidative stress and innovative therapies: New Emerging Team, Principal-Investigator Team Leader: J. Brien  $250,000 ($1,250,000) Apr02-07
CIHR Multiple courses of antenatal corticosteroids for preterm  Birth: A 5 year follow-up (MACS-5) Clinical Trial: Co-Investigator (PI; E.. Asztalos). Member of Steering Committee $512,165 ($4,799,770) Oct05-09
BHF Transgenerational programming of cardiovascular and adrenal function following maternal nutrient restriction Operating, Co-Principle Investigator (M. Hanson) £62,618 (£156,542) UK £ Jan03-06
CIHR Multiple versus single courses of antenatal corticosteroids in preterm birth. Clinical Trial: Co-Investigator (PI; K. Murphy). Member of Steering Committee. $680,000 ($4,799,770) Mar00-07
CIHR Development of the cortisol stress response in infants: Influence of gene-environment interactions
Operating Award. Co-Investigator (PI; L. Atkinson)
$148,543 ($594,172) Oct03-07
CIHR Mechanism of impaired HPA axis and its responsiveness to hypoglycemia, exercise and stress in diabetes: Adaptive changes in brain, pituitary, pancreas and adrenal Co-Investigator (PI; M. Vranic) $159,709 ($798,545) Jan02-07
Juvenile Diabetes Foundation

Mechanisms of effects of insulin, hyperglycemia and leptin on the relationship between the HPA axis and counter- US regulation in diabetes: Co-Principal Investigator PI: Mladen Vranic

 $127,000 ($347,000) Jul03-06

Abbreviations:
BHF British Heart Foundation
CIHR Canadian Institutes of Health Research
NSERC Natural Sciences and Engineering Research Council of Canada

Current Training Grants:
CIHR Genes, Environment & Health Training Grant
Training Grant: SGM Ontario Director and member
of Executive Group. PI: Michael Meaney, Montreal 
$240,000 ($1,440,000) Apr03-09

Description:
Programming of HPA function and behaviour
The major research focus of the lab is to understand the mechanisms of hypothalamo-pituitary-adrenocortical (HPA) development, and how these mechanisms can be modified or programmed by fetal environment. This is important because a number of adult pathologies, including diabetes, hypertension and depression, have been associated with chronic changes in HPA function. We are particularly interested in establishing the effects of fetal exposure to glucocorticoids, maternal stress and nutrient restriction on development of neuroendocrine function and behaviour. These studies are clinically relevant because pregnant women, at risk of delivering prematurely are treated with glucocorticoids to mature the fetal lungs. However, there is little information concerning the effects of early glucocorticoid exposure on the developing brain. The effects of these perturbations on brain and neuroendocrine development are not known.

Recent/Key Publications:
Andrews, M.H. and Matthews, S.G. Programming of the hypothalamo-pituitary-adrenal axis: Serotonergic involvement. Stress (2004), 7(1): 15-27.

Andrews, M.H., Kostaki, A., Setiawan, E., McCabe, L., Owen, D., Banjanin, S. and Matthews, S.G. Developmental regulation of 5-HT1A receptor mRNA in the fetal limbic system: Response to antenatal glucocorticoid. Dev. Brain Research (2004), 149(1): 39-44.

Andrews, M.H., Kostaki, A., Setiawan, E., McCabe, L., Owen, D., Banjanin, S. and Matthews, S.G. Developmental regulation of 5-HT7 receptor and NGFI-A in the guinea pig hippocampus: Influence of glucocorticoid. Journal of Physiology (2004), 555(3): 659-670.

Owen, D., Setiawan, E., Li, A., McCabe, L and Matthews, S.G. Regulation of NMDA Receptor Subunit Expression in the Fetal Guinea Pig Brain. Biology of Reproduction (2004). 71(2):676-683.

Setiawan, E., Owen, D., Andrews, M.A., McCabe, L. and Matthews S.G. Glucocorticoids do not alter developmental expression of steroid receptor co-activator (SRC) 1 and 2 in the fetal guinea pig hippocampus and pituitary. Endocrinology (2004). 145(8):3796-3803.

Banjanin, S., Kapoor, A. & Matthews, S.G. Prenatal glucocorticoid exposure alters hypothalamo-pituitary-adrenal function and blood pressure in mature male guinea pigs. Journal of Physiology (2004). 558(Pt 1):305-518.

Akirav, E.M., Chan, O., Inouye, K., Riddell, M.C. Matthews, S.G. and Vranic, M. Partial leptin restoration markedly improves metabolic profile in STZ-diabetic rats. Metabolism (2004). I53(12)1558-1564.

Matthews, S.G, Owen, D., Kalabis, G., Banjanin, S., Setiawan, E.B., Dunn, E.A. and Andrews, M.H.. Fetal glucocorticoid exposure and hypothalamo-pituitary-adrenal (HPA) function after birth. Endocrine Research (2004) 30(4):827-836.

Owen, D., Andrews, M.H. and Matthews S.G. Maternal adversity, glucocorticoids and neuroendocrine function and behaviour. Neuroscience and Biobehavioural Reviews (2005) 29(2):209-226.

Chan, O., Inouye, K., Akirav, E., Park, E., Riddell, M.C., Vranic, M. and Matthews, S.G. Insulin alone increases hypothalamo-pituitary-adrenal activity and diabetes lowers the ceiling for maximal activation of the HPA axis. Endocrinology (2005) 146(3):1382-1390.

Inouye, K., Chan, O., Yue, J.T., Matthews, S.G and Vranic, M. Effects of diabetes and recurrent hypoglycemia on the regulation of the sympathoadrenal system and hypothalamo-pituitary-adrenal (HPA) axis. American Journal of Physiology (2005). 288(2):E422-E429.

Chan, O., Inouye, K., Akirav, E., Park, E., Riddell, M.C., Matthews, S.G. and Vranic, M. Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal (HPA) activity in diabetes, but it does impair the HPA response to insulin-induced hypoglycemia. American Journal of Physiology (2005), 29(2):209-226.

Owen, D., Banjanin, S., Gidrewicz, D., McCabe, L. and Matthews, S.G. Guinea Pig Hypothalamic-Pituitary-Adrenal Development: Sensitivity to Glucocorticoids. Journal of Neuroendocrinology (2005). 17(4):220-226.

Chan, S.Y., Andrews, M.H., Lingas, R.I., McCabe, C.J., Franklyn, J.A., Kilby, M.D. and Matthews, S.G. The effect of maternal nutrient deprivation on thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain is sex dependent. Journal of Physiology (2005), 566:467-480.

Kalabis, G. M. Kostaki, A., Andrews, M.H., Petropoulos, S., Gibb, W. and Matthews, S.G. Development of multidrug resistance phosphoglycoprotein mRNA (mdr1a and mdr1b) and protein expression in the murine placenta: Fetal protection during pregnancy. Biology of Reproduction (2005), 73(4)591-597.

Sun, M., Kingdom, J., Baczyk, D., Matthews, S. G. and Gibb, W. Expression of the multidrug resistance P-glycoprotein, (Mdr-1/P-gp) in the human placenta decreases with advancing gestation. Placenta (2005). Sep 2; [Epub ahead of print].

Kapoor, A. and Matthews S.G. Short periods of prenatal stress affects growth, behaviour, and HPA axis activity in male guinea pig offspring. Journal of Physiology (2005), 566(3): 967-977.

Iqbal, U., Brien, J.F., Banjanin, S., Andrews, M.H., Matthews, S.G, Reynolds, J.N. Chronic prenatal ethanol exposure alters glucocorticoid signaling in the hippocampus of the postnatal guinea pig. Journal of Neuroendocrinology (2005), 17(9):600-608.

Park, E., Chan, O., Li, Q., Kiraly, M., Matthews, S.G., Vranic, M. and Riddell, M.C. Changes in basal hypothalamo-pituitary-adrenal (HPA) activity during exercise training are centrally mediated. American Journal of Physiology: Integrative and Comparative Physiology (2005), 289:R1360-1371.

Erdeljan, P. Andrews, M.H., MacDonald, J.F. and Matthews, S.G. Glucocorticoids and serotonin alter glucocorticoid receptor mRNA levels in fetal guinea pig hippocampal neurons, in vitro. Reproduction, Fertility & Development (2005), 17(7):743-749.

Inouye K, Yue JTY, Chan O, Kim T, Akirav EM, Park E, Riddell MC, Matthews SG, Vranic M. Effects of recurrent hypoglycemia on hypoglycemic counterregulation and adrenal catecholamine-synthesizing enzymes in insulin-treated diabetic rats. Endocrinology (2005), In Press.

Kapoor, A, Dunn, EA, Kostaki, A, Andrews, MH, Matthews, SG. Fetal programming of hypothalamo-pituitary-adrenal (HPA) function: Prenatal stress and glucocorticoids. Journal of Physiology (2006) Feb 9 [E-Pub ahead of print].

Book Chapters: Published

Matthews, S.G. Development of the Hypothalamo-Pituitary-Adrenal Axis in ‘Textbook of Pediatric Endocrinology’. McGraw-Hill (2001), Chapter 8, pp200-212.

Matthews, S.G. ‘Antenatal glucocorticoids and programming of the developing brain’ in ‘The Newborn Brain- Scientific Basis and Clinical Applications’. Eds H. Lagercrantz & M. Hanson. Cambridge University Press (2001), Chapter 22, pp508-528.

Matthews, S. G. and Meaney, M. J. ‘Maternal Adversity, Vulnerability and Disease’ pp28-49 in ‘"Perinatal Stress, Mood and Anxiety Disorders: From Bench to Bedside" "Bibliotheca Psychiatrica N. 173" Eds A. Riecher-Rossler & M. Steiner. Karger (2005).

Matthews, S. G. and Phillips, D.I.W. Neuroendocrine programming of adult disease: current perspectives and future directions In Perinatal Programming: Early Life Determinants of Adult Health & Disease. Eds D. Hodgson & C. Coe. Taylor & Francis Medical Books (2005).