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Department of Physiology, Development and Neuroscience

 

Research

Development and regulation of endocrine systems in the fetus

These studies have examined the bioavailability of hormones in the fetus, in particular, the glucocorticoids, thyroid hormones, leptin, insulin-like growth factors and the renin-angiotensin system.  Analyses of hormone systems in utero have included measurements of circulating concentrations, tissue metabolism and metabolic enzymes, cellular uptake mechanisms and receptor expression.  These studies have demonstrated complex interactions between endocrine systems before birth and have elucidated a variety of cellular and molecular mechanisms of developmental control.

Hormonal control of fetal growth, development and maturation

My research has investigated the role of hormones in the regulation of normal fetal development.  These studies have an integrative approach by examining a wide variety of fetal tissues and organs, and aspects of fetal physiology, including growth, cardiovascular, lung and renal function, nutrition and metabolism.  In particular, several of these studies have established the importance of endocrine signals in fetal maturation near to delivery and in the successful transition from the intrauterine to extrauterine environment at birth.  I have investigated the mechanisms of glucocorticoid action in several physiological systems, and demonstrated the key roles of other hormones, such as thyroid hormones and angiotensin II, in mediating many of the maturational effects of glucocorticoids.

Overall, my research has an integrative approach to the study of mammalian endocrinology and systems animal physiology.  The research findings have important implications for the understanding of normal fetal growth and development; the consequences of prematurity, intrauterine growth retardation and fetal endocrine disorders; and the mechanisms underlying the developmental programming of adult (patho)physiology. 

Collaborators

Professor Abigail Fowden, PDN, University of Cambridge
Dr Dino Giussani, PDN, University of Cambridge
Dr Sue Ozanne, Institute of Metabolic Science, University of Cambridge
Professor Gordon Smith, Department of Obstetrics and Gynaecology, University of Cambridge
Dr Dominique Blache, University of Western Australia, Australia
Professor Min Du, Department of Animal Sciences, Washington State University
Professor Richard Oreffo, Institute of Developmental Sciences, University of Southampton
Dr Theo Visser, Erasmus Medical Center, Rotterdam, The Netherlands
Dr Sean Limesand, University of Arizona, Tucson, USA

Publications

Key publications: 

Camm EJ, Inzani I, De Blasio MJ, Davies KL, Lloyd IR, Wooding FBP, Blache D, Fowden AL, Forhead AJ, (2020), Thyroid hormone deficiency suppresses fetal pituitary-adrenal function near term: implications for the control of fetal maturation and parturition, Thyroid (in press)

Davies KL, Camm JE, Atkinson EV, Lopez T, Forhead AJ, Murray AJ, Fowden AL, (2020), Development and thyroid hormone dependence of skeletal muscle mitochondrial function towards birthJournal of Physiology, 598: 2453-2468

Harris SE, De Blasio MJ, Zhao X, Ma M, Davies KL, Wooding FBP, Hamilton RS, Blache D, Meredith D, Murray AJ, Fowden AL, Forhead AJ, (2020), Thyroid deficiency before birth modifies the adipose transcriptome to promote overgrowth of white adipose tissue and impair thermogenic capacity, Thyroid, 30: 794-805

De Blasio MJ, Lanham SA, Blache D, Oreffo ROC, Fowden AL, Forhead AJ, (2018), Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus, American Journal of Physiology, 314: R781-R790

Harris SE, De Blasio MJ, Davis MA, Kelly A, Davenport HM, Wooding FBP, Blache D, Meredith D, Anderson M, Fowden AL, Limesand SW, Forhead AJ, (2017), Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation, Journal of Physiology, 595: 3331-3343

De Blasio MJ, Boije M, Kempster SL, Smith GCS, Charnock-Jones DS, Denyer A, Hughes A, Wooding FBP, Blache D, Fowden AL, Forhead AJ, (2016), Leptin matures aspects of lung structure and function in the ovine fetus, Endocrinology, 157: 395-404

De Blasio MJ, Boije M, Bernstein BS, Davies KL, Plein A, Kempster SL, Smith GCS, Charnock-Jones DS, Blache D, Wooding FBP, Giussani DA, Fowden AL, Forhead AJ, (2015), Developmental expression and glucocorticoid control of the leptin receptor in fetal lung, PLoS One, 10(8): e0136115

Forhead AJ, JellymanJK, De BlasioMJ, JohnsonE, GiussaniDA, Broughton PipkinF, FowdenAL, (2015), Maternal dexamethasone treatment alters circulating and tissue components of the renin-angiotensin system in the pregnant ewe and fetus, Endocrinology, 156: 3038-3046

Jellyman JK, Cripps RL, Martin-Gronert MS, Giussani DA, Ozanne SE, Shen QW, Du M, Fowden AL, Forhead AJ, (2012), Effects of cortisol and dexamethasone on insulin signalling pathways in skeletal muscle of the ovine fetus during late gestation, PLoS One, 7(12): e52363

Lanham SA, Fowden AL, Roberts C, Oreffo ROC, Cooper C, Forhead AJ, (2011), Effects of hypothyroidism on the structure and mechanical properties of bone in the ovine fetus, Journal of Endocrinology, 210: 189-198

Forhead AJ, Lamb CA, Franko KL, O’Connor DM, Wooding FBP, Cripps RL, Ozanne S, Blache D, Shen QW, Du M, Fowden AL, (2008), Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation, Journal of Physiology, 586: 2393-2403

Forhead AJ, Jellyman JK, Gardner DS, Giussani DA, Kaptein E, Visser TJ, Fowden AL, (2007), Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus, Endocrinology, 148: 800-805

O’Connor DM, Blache D, Hoggard N, Brookes E, Wooding FBP, Fowden AL, Forhead AJ, (2007), Developmental control of plasma leptin and adipose leptin mRNA in the ovine fetus during late gestation: role of glucocorticoids and thyroid hormones, Endocrinology, 148: 3750-3757

Reviews

Forhead AJ & Fowden AL (2018) Formation and growth of the fetus. In M. K. Skinner (Ed.), Encyclopedia of Reproduction. vol. 3, pp. 370–379. Academic Press: Elsevier

Forhead AJ, Fowden AL, (2014), Thyroid hormones in fetal growth and prepartum maturation, Journal of Endocrinology, 221: R87-R103

Forhead AJ, Fowden AL, (2011), Chapter 7, The consequences for preterm infants of antenatal glucocorticoid treatment, In Birth Rites and Rights, Eds Ebtehaj F, Herring J, Johnson MH & Richards M. Hart Publishing, pp. 129-149

Forhead AJ, Fowden AL, (2009), The hungry fetus? Role of leptin as a nutritional signal before birth, Journal of Physiology, 587: 1145-1152

Teaching and Supervisions

Teaching: 

Lecturer in Part II PDN P3 Placental and Fetal Physiology

Demonstrator in histology

University Lecturer
Dr Alison J Forhead

Contact Details

+44 (0) 1223 333853/766125, Fax: +44 (0) 1223 333840