Peter King

Senior Lecturer in Endocrinology

Peter King graduated from Cambridge University with a degree in Natural Sciences. He was awarded a PhD by the Imperial Cancer Research Fund (now CRUK) on transcriptional regulation of the human beta interferon gene, with studies performed at Lincolns Inn Fields and St Georges Hospital Medical School, London. He joined the Molecular Endocrinology Department at Bart’s in 1997, was appointed to a lectureship in 2001 and was promoted to Senior Lecturer in 2009.

Research interests:

  • Control of adrenal development and differentiation
  • Sonic hedgehog and BMP signalling in endocrine systems
  • Adrenocortical cell signalling and steroidogenesis
  • Adrenocortical stem cells and cancer stem cells
  • Mechanisms of adrenocortical cancer
  • Transcriptional regulation in the adrenal cortex
  • Transcriptional regulation during adipocyte differentiation
  • Control of adipocyte differentiation

Summary of Research

Adrenal Development

The main aim of my research is to understand the molecular mechanisms that control adrenal development and differentiation during organogenesis, and homeostasis in the adult. The adrenal is a vitally important gland that controls both the stress response and blood volume and, as such, disorders of development and function can be fatal without lifelong therapeutic intervention. Previous research has identified sonic hedgehog (Shh) as an important signalling molecule in adrenal development and has proposed that the cells that produce it and/or the signal receiving cells in the adrenal capsule, are candidates for stem/progenitor cells in development and in the adult. Current research is focussing on potential signalling pathways that control Shh signalling or are downstream of it in the adrenal, for example, Wnt/b catenin, FGF and Dlk1 pathways, and the control that these exert over adrenal remodelling in the adult, which is the concerted response of the gland to stress or changes in blood volume that require the rapid recruitment of new steroidogenic cells. It is anticipated that these will prove to be novel targets for treatment of hypertension.

More recently we have begun to investigate the role of primary cilia (see also Chapple) in adrenal development and function and the shared origins of adrenal and testicular steroidogenic (Leydig) cells, as well as continuing to study signalling pathways that control steroidogenesis and are involved in adrenal cell growth and cancer.


Dlk1 mRNA and DLK1 protein is a marker of the outer ZU.
Adult rat adrenal sections were processed for Dlk1 NR-ISH (B) and then stained with antibodies to CYP11B1 (B1) and CYP11B2 (B2) (A, both green). The Dlk1 signal was pseudocoloured to red (C) and the merged image (D) assembled. White arrows indicate CYP11B2 positive/Dlk1 negative cells while the yellow arrows indicate a minority of double positive cells. The same result was obtained with an anti-Dlk1 antibody (inset). Taken from Guasti et al. (2013), Endocrinology 154: 4675-4684.

Members of the Group

PhD students: Dominic Cavlan, Candy Sze.

Key Publications

Noon, LA, Bakmanidis, A, Clark, AJL, O’Shaughnessy, P J and King, P.J (2006) Identification of a novel MC2-R splice variant in murine adipocytes: Implications for post-transcriptional control of expression during adipogenesis. J. Mol. Endocrinol., 37: 415-420. 10.1677/jme.1.02023

Noon, LA, Clark, AJL, O’Shaughnessy, P J. and King, P.J. (2006) A C/EBP site at -87 is required for the activation of a novel murine melanocortin 2-receptor (MC2-R) promoter at late stages during adipogenesis. Endocrinol., 147: 6019-6026. 10.1210/en.2006-0867

Bogdarina, I, Welham, S, King, PJ, Burns, SP and Clark, AJL (2007) Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ. Res., 100: 520-526. 10.1161/01.RES.0000258855.60637.58

Johnston, H, King, PJ and O’Shaughnessy, PJ (2007) Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis, Reproduction, 133:1181-1187. 10.1530/REP-06-0359

Hu, L, Monteiro, A, Johnston, H, King, P and O'Shaughnessy, PJ (2007) Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis. Reproduction, 134:585-591. 10.1530/REP-07-0133

Doufexis, M, Storr, HL, King, PJ and Clark, AJL (2007) Interaction of the melanocortin 2 receptor with nucleoporin 50: Evidence for a novel pathway between a G-protein-coupled receptor and the nucleus. FASEB J., 21: 4095-4100. 10.1096/fj.06-7927com

Janes, ME, Chu, KME, Clark, AJL and King, PJ (2008) Mechanisms of adrenocorticotropin-induced activation of ERK1/2 MAP kinase in the human H295R adrenal cell line. Endocrinol., 149: 1898-1905. 10.1210/en.2007-0949

Chung, TT, Webb, TR, Chan, LF, Cooray, SN, Metherell, LA, King, PJ, Chapple, JP and Clark, AJL (2008) The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface. J. Clin. Endocrinol. Metab., 93: 4948-4954. 10.1210/jc.2008-1744

King, PJ, Guasti, L and Laufer, E (2008) Hedgehog signalling in endocrine development and disease. J. Endocrinol., 198: 439-450. 10.1677/JOE-08-0161

Bogdarina, IG, King, PJ and Clark, AJL (2009) Characterisation of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids. J. Mol. Endocrinol., 43: 73-80. 10.1677/JME-09-0036

Garcia, EA, King, P, Sidhu, K, Ohgusu, H, Walley, A, Lecoeur, C, Gueorguiev, M, Khalaf, S, Davies, D, Grossman, AB, Kojima, M, Petersenn, S, Froguel, P and Korbonits, M (2009) The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes. Eur. J. Endocrinol., 161: 307-315. 10.1530/EJE-09-0122

King, P, Paul, A and Laufer, E (2009) Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. PNAS, 106: 21185-21190. 10.1016/j.ydbio.2009.05.387

Igreja, S, Chahal, HS, King, P, Bolger, GB, Srirangalingam, U, Guasti, L, Chapple, JP, Trivellin, G, Gueorguiev, M, Guegan, K, Stals, K, Khoo, B, Kumar, AV, Ellard, S, Grossman, AB, Korbonits, M. and the International FIPA consortium (2010) Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Human Mutation, 8: 950-960. 10.1002/humu.21292

Guasti, L, Paul, A, Laufer, E and King, P (2011) Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex. Mol. Cell. Endocrinol., 336: 117-122. 10.1016/j.mce.2010.11.010

Gorrigan, RJ, Guasti, L, King, P, Clark, AJL and Chan, LF (2011) Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland. J. Mol. Endocrinol., 46: 227-232. 10.1530/JME-11-0011

Laufer, E, Kesper, D, Vortkamp A and King, P (2012) Sonic hedgehog signaling during adrenal development. Mol. Cell. Endocrinol., 351: 19-27. 10.1016/j.mce.2011.10.002

Hughes, CR, Guasti, L, Meimaridou, M, Chuang, C-H, Schimenti, JC, King, PJ, Costigan, C, Clark, AJL and Metherell, LA (2012) Mini chromosome maintenance-deficient 4 homologue (MCM4) mutation is associated with adrenal failure, natural killer cell deficiency and increased chromosomal fragility. J. Clin. Invest., 122: 814-820.

Meimaridou, E, Kowalczyk, J, Guasti, L, Hughes, CR, Wagner, F, Frommolt, P, Nürnberg, P, Mann, NP, Banerjee, R, Saka, HN, Chapple, JP, King, PJ, Clark, AJL and Metherell, L.A. (2012) Mutations in nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency. Nat. Genet., 44: 740-742. 10.1038/ng.2299

Thompson, IR, Chand, AN, King, PJ, Ansorge, O, Karavitaki, N, Jones, CA, Rahmutula, D, Gardner, DG, Zivkovic, V, Wheeler-Jones, CP, McGonnell, IM, Korbonits, M, Anderson, RA, Wass, JAH, McNeilly, AS and Fowkes, RC (2012) Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide. Endoc. Related Cancer, 19: 497-508. 10.1530/ERC-12-0129

Marion, V, Mockel, A, de Melo, C, Obringer, C, Claussmann, A, Simon, A, Messaddeq, N, Durand, M, Dupuis, L, Loeffler, J-P, King, P, Mutter-Schmidt, C, Petrovsky, N, Stoetzel, C and Dollfus, H (2012) BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metab., in press. 10.1016/j.cmet.2012.08.005

PubLists Publications

Guasti L, Cavlan D, Cogger K et al. (2013). Dlk1 up-regulates Gli1 expression in male rat adrenal capsule cells through the activation of β1 integrin and ERK1/2.. Endocrinology Vol.154, (12) 4675-4684.
10.1210/en.2013-1211
Guasti L, Candy Sze WC, McKay T et al. (2013). FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development.. Mol Cell Endocrinol Vol.371, (1-2) 182-188.
10.1016/j.mce.2013.01.014
Meimaridou E, Hughes CR, Kowalczyk J et al. (2013). Familial glucocorticoid deficiency: New genes and mechanisms.. Mol Cell Endocrinol Vol.371, (1-2) 195-200.
10.1016/j.mce.2012.12.010
Yates R, Katugampola H, Cavlan D et al. (2013). Adrenocortical development, maintenance, and disease.. Curr Top Dev Biol Vol.106, () 239-312.
10.1016/B978-0-12-416021-7.00007-9
Marion V, Mockel A, De Melo C et al. (2012). BBS-Induced Ciliary Defect Enhances Adipogenesis, Causing Paradoxical Higher-Insulin Sensitivity, Glucose Usage, and Decreased Inflammatory Response. CELL METABOLISM Vol.16, (3) 1550-4131 363-377.
10.1016/j.cmet.2012.08.005
Thompson IR, Chand AN, King PJ et al. (2012). Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide.. Endocr Relat Cancer Vol.19, (4) 497-508.
10.1530/ERC-12-0129
Meimaridou E, Kowalczyk J, Guasti L et al. (2012). Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency.. Nat Genet Vol.44, (7) 740-742.
10.1038/ng.2299
Laufer E, Kesper D, Vortkamp A et al. (2012). Sonic hedgehog signaling during adrenal development. MOLECULAR AND CELLULAR ENDOCRINOLOGY Vol.351, (1) 0303-7207 19-27.
10.1016/j.mce.2011.10.002
Hughes CR, Guasti L, Meimaridou E et al. (2012). MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. JOURNAL OF CLINICAL INVESTIGATION Vol.122, (3) 0021-9738 814-820.
10.1172/JCI60224
Gorrigan RJ, Guasti L, King P et al. (2011). Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland.. J Mol Endocrinol Vol.46, (3) 227-232.
10.1530/JME-11-0011
Guasti L, Paul A, Laufer E et al. (2011). Localization of Sonic hedgehog secreting and receiving cells in the developing and adult rat adrenal cortex.. Mol Cell Endocrinol Vol.336, (1-2) 117-122.
10.1016/j.mce.2010.11.010
Igreja S, Chahal HS, King P et al. (2010). Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.. Hum Mutat Vol.31, (8) 950-960.
10.1002/humu.21292
Laufer E, King P, Paul A (2010). Shh signaling regulates adrenocortical development and identifies novel progenitors of steroidogenic lineages. ENDOCR J Vol.57, () 0918-8959 S309-S309.
King P, Paul A, Laufer E (2009). Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages.. Proc Natl Acad Sci U S A Vol.106, (50) 21185-21190.
10.1073/pnas.0909471106
Bogdarina IG, King PJ, Clark AJ (2009). Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids.. J Mol Endocrinol Vol.43, (2) 73-80.
10.1677/JME-09-0036
Garcia EA, King P, Sidhu K et al. (2009). The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes.. Eur J Endocrinol Vol.161, (2) 307-315.
10.1530/EJE-09-0122
Laufer E, Paul A, King PJ (2009). Shh signaling regulates adrenocortical development and identifies novel progenitors of steroidogenic lineages. DEVELOPMENTAL BIOLOGY Vol.331, (2) 0012-1606 490-490.
10.1016/j.ydbio.2009.05.387
Chung TT, Webb TR, Chan LF et al. (2008). The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface.. J Clin Endocrinol Metab Vol.93, (12) 0021-972X 4948-4954.
10.1210/jc.2008-1744
King PJ, Guasti L, Laufer E (2008). Hedgehog signalling in endocrine development and disease. J ENDOCRINOL Vol.198, (3) 0022-0795 439-450.
10.1677/JOE-08-0161
Janes ME, Chu KM, Clark AJ et al. (2008). Mechanisms of adrenocorticotropin-induced activation of extracellularly regulated kinase 1/2 mitogen-activated protein kinase in the human H295R adrenal cell line.. Endocrinology Vol.149, (4) 0013-7227 1898-1905.
10.1210/en.2007-0949
Doufexis M, Storr HL, King PJ et al. (2007). Interaction of the melanocortin 2 receptor with nucleoporin 50: evidence for a novel pathway between a G-protein-coupled receptor and the nucleus.. FASEB J Vol.21, (14) 4095-4100.
10.1096/fj.06-7927com
Hu L, Monteiro A, Johnston H et al. (2007). Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis. REPRODUCTION Vol.134, (4) 1470-1626 585-591.
10.1530/REP-07-0133
Johnston H, King PJ, O'Shaughnessy PJ (2007). Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis. REPRODUCTION Vol.133, (6) 1470-1626 1181-1187.
10.1530/REP-06-0359
Bogdarina I, Welham S, King PJ et al. (2007). Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension.. Circ Res Vol.100, (4) 520-526.
10.1161/01.RES.0000258855.60637.58
Noon LA, Clark AJ, O'Shaughnessy PJ et al. (2006). A CCAAT/enhancer-binding protein site at -87 is required for the activation of a novel murine melanocortin 2-receptor promoter at late stages during adipogenesis.. Endocrinology Vol.147, (12) 0013-7227 6019-6026.
10.1210/en.2006-0867
Noon LA, Bakmanidis A, Clark AJL et al. (2006). Identification of a novel melanocortin 2 receptor splice variant in murine adipocytes: implications for post-transcriptional control of expression during adipogenesis. J MOL ENDOCRINOL Vol.37, (3) 0952-5041 415-420.
10.1677/jme.1.02023
White NR, Mulligan P, King PJ et al. (2006). Sodium butyrate-mediated Sp3 acetylation represses human insulin-like growth factor binding protein-3 expression in intestinal epithelial cells.. J Pediatr Gastroenterol Nutr Vol.42, (2) 0277-2116 134-141.
10.1097/01.mpg.0000189345.31010.89
Noon LA, Clark AJ, King PJ (2004). A peroxisome proliferator-response element in the murine mc2-r promoter regulates its transcriptional activation during differentiation of 3T3-L1 adipocytes.. J Biol Chem Vol.279, (22) 0021-9258 22803-22808.
10.1074/jbc.M401861200
King P, CLARK AJL, Noon LA (2004). A Peroxisome Proliferator-response Element in the Murine mc2-r Promoter Regulates Its Transcriptional Activation during Differentiation of 3T3-L1 Adipocytes. Journal of Biological Chemistry Vol.279, (22) 0021-9258 22803-22808.
10.1074/jbc.M401861200
Swords FM, Noon LA, King PJ et al. (2004). Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missense mutations in the MC2R gene.. Mol Cell Endocrinol Vol.213, (2) 0303-7207 149-154.
10.1016/j.mce.2003.10.052
Fowkes RC, Desclozeaux M, Patel MV et al. (2003). Steroidogenic factor-1 and the gonadotrope-specific element enhance basal and pituitary adenylate cyclase-activating polypeptide-stimulated transcription of the human glycoprotein hormone alpha-subunit gene in gonadotropes. MOL ENDOCRINOL Vol.17, (11) 0888-8809 2177-2188.
10.1210/me.2002-0393
Fowkes RC, Sidhu KK, Sosabowski JK et al. (2003). Absence of pituitary adenylate cyclase-activating polypeptide-stimulated transcription of the human glycoprotein alpha-subunit gene in LbetaT2 gonadotrophs reveals disrupted cAMP-mediated gene transcription.. J Mol Endocrinol Vol.31, (2) 0952-5041 263-278.
10.1677/jme.0.0310263
Clark AJL, Baig AH, Noon L et al. (2003). Expression, desensitization, and internalization of the ACTH receptor (MC2R). MELANOCORTIN SYSTEM Vol.994, () 0077-8923 111-117.
Swords FM, Baig A, Malchoff DM et al. (2002). Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity.. Mol Endocrinol Vol.16, (12) 0888-8809 2746-2753.
10.1210/me.2002-0099
Baig AH, Swords FM, Szaszák M et al. (2002). Agonist activated adrenocorticotropin receptor internalizes via a clathrin-mediated G protein receptor kinase dependent mechanism.. Endocr Res Vol.28, (4) 0743-5800 281-289.
10.1081/ERC-120016798
Kosti O, King PJ, Hinson JP (2002). Tumour-derived human adrenocortical cells express beta-adrenergic receptors: steroidogenic effects of beta-adrenergic input.. Endocr Res Vol.28, (4) 0743-5800 363-367.
10.1081/ERC-120016810
Fowkes RC, King P, Burrin JM (2002). Regulation of human glycoprotein hormone alpha-subunit gene transcription in L beta T2 gonadotropes by protein kinase C and extracellular signal-regulated kinase 1/2. BIOL REPROD Vol.67, (3) 0006-3363 725-734.
10.1095/biolreprod67.3.725
Noon LA, Franklin JM, King PJ et al. (2002). Failed export of the adrenocorticotrophin receptor from the endoplasmic reticulum in non-adrenal cells: evidence in support of a requirement for a specific adrenal accessory factor.. J Endocrinol Vol.174, (1) 0022-0795 17-25.
10.1677/joe.0.1740017
Baig AH, Swords FM, Noon LA et al. (2001). Desensitization of the Y1 cell adrenocorticotropin receptor: evidence for a restricted heterologous mechanism implying a role for receptor-effector complexes.. J Biol Chem Vol.276, (48) 0021-9258 44792-44797.
10.1074/jbc.M108572200
Newell-Price J, King P, Clark AJ (2001). The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression.. Mol Endocrinol Vol.15, (2) 0888-8809 338-348.
10.1210/mend.15.2.0599
KING PJ, Clark AJL, Newell-Price J (2001). Methylation of a tissue-specific CpG island in normal non-expressing human tissue. Mol Endo Vol.15, () 338-348.

Sponsors

Medical Research Council

Wellcome Trust

 

Collaborators

Internal: Dr Leo Guasti (WHRI);
External: Dr Ed Laufer (Columbia University, New York, USA); Dr Vincent Marion (University of Strasbourg, France); Prof Peter O’Shaughnessy (Glasgow University).

Contact

Dr Peter King
Centre for Endocrinology
William Harvey Research Institute
Charterhouse Square
London, EC1M 6BQ
T: +44 (0) 20 7882 6237
Skype: peterking1
E: This email address is being protected from spambots. You need JavaScript enabled to view it.

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