Dr. Radovick’s research focuses on the development, regulation and dysregulation of hypothalamic-pituitary function, for which she is currently 95 percent funded by the NIH.
Her research centers on determining the regulation of the gonadotropin-releasing hormone (GnRH) gene. It has a central role in reproduction by controlling secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn regulate the synthesis of estrogen and androgen. Her group was one of the first to generate GnRH-expressing neuronal cell-lines and map GnRH cell-specific elements in vivo. She also studies intracellular signaling pathways within the GnRH neuron. Her lab demonstrated that insulin-like growth factor (IGF-1) receptors were present on GnRH neurons obtained from transgenic animals and their activation results in increased transcription of the GnRH gene. This pathway may be an important mediator of GnRH expression in normal puberty as well as in disorders resulting in abnormal pubertal development and reproduction.
The other major area of this research has been to characterize the transcription factors important for normal pituitary development. Her initial studies provided the first description in man of the molecular genetic mechanism for combined pituitary hormone deficiency; this involved a mutation in the Pit-1 gene that is necessary for the differentiation of the somatotroph (growth hormone-producing cell), lactotroph (prolactin) and thyrotroph (thyrotropin) lineages. More recently, her laboratory has begun investigation into the molecular mechanisms by which mutations in other transcription factors important for pituitary development exert their effects.
Function of Metformin at the Cellular Level and Best Dosing for Children and Adults With DM or Pre-DM
Pine-Twaddell ED, Romero CJ, Radovick S. "Vertical transmission of hypopituitarism: Critical importance of appropriate interpretation of thyroid function tests and levothyroxine therapy during pregnancy." Thyroid. 2013 Feb 11. PMID: 23397938
Novaira HJ, Fadoju D, Diaczok D, Radovick S. "Genetic mechanisms mediating kisspeptin regulation of GnRH gene expression." J Neurosci. 2012, 32(48):17391-400. PMID: 23197730.
Romero CJ, Pine-Twaddell E, Sima DI, Miller RS, He L, Wondisford F, Radovick S. "Insulin-like growth factor-mediates negative feedback to somatotroph GH expression via POU1F1/CREB-binding protein interactions." Mol Cell Biol. 2012, 32(21):4258-69. PMID: 22890843
He L, Naik K, Meng S, Cao J, Sidhaye AR, Ma A, Radovick S, Wondisford FE. "Transcriptional co-activator p300 maintains basal hepatic gluconeogenesis." J Biol Chem. 2012, 14;287(38):32069-77. PMID: 22815486
Raivio T, Avbelj M, McCabe MJ, Romero CJ, Dwyer AA, Tommiska J, Sykiotis GP, Gregory LC, Diaczok D, Tziaferi V, Elting MW, Padidela R, Plummer L, Martin C, Feng B, Zhang C, Zhou QY, Chen H, Mohammadi M, Quinton R, Sidis Y, Radovick S, Dattani MT, Pitteloud N. "Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia." J Clin Endocrinol Metab. 2012, 97(4):E694-9. PMID: 22319038
Zanger K, Radovick S, Wondisford, FE. CREB Binding protein recruitment to the transcription complex requires growth factor-dependent phosphorylation of its GF Box. Mol Cell 7:551-558, 2001.
Wolfe A, Kim HH, Tobet S, Stafford DEJ, Radovick S. Identification of promoter elements that are essential and sufficient for cell specific expression of the human GnRH gene. Mol Endocrinol 16:435-449, 2002.
Kim HH, Wolfe A, Tobet S, Radovick S. Identification of a molecular switch directing differential expression of hypothalamic and ovarian GnRH. J Biol Chem 277:5194-5202, 2002.
Radovick S. Molecular Mechanisms Responsible for Combined Pituitary Hormone Deficiency. J Clin Endocrinol Metab 15:1427-1428, 2002.
Cohen RN, Cohen LE, Botero D, Yu C, Sagar A, Jurkiewicz M, Radovick S. Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. J Clin Endo Metab 88(10):4832-4839, 2003.
Wilson TA, Rose SR, Cohen P, Rogol AD, Backeljauw P, Brown R, Hardin DS, Kemp SF, Lawson M, Radovick S, Rosenthal SM, Silverman L, Speiser P. Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr 143(4):415-21, 2003.
Cohen RN, Brue T, Naik K, Houlihan CA, Wondisford FE, Radovick S. The role of CBP/p300 interactions and Pit-1 dimerization in the pathophysiological mechanism of combined pituitary hormone deficiency. J Clin Endocrinol Metab. 91(1):239-47, 2006.
Buggs C, Weinberg F, Kim E, Wolfe A, Radovick S, Wondisford F. Insulin augments GnRH-stimulated LHbeta gene expression by Egr-1. Mol Cell Endocrinol. 249(1-2):99-106, 2006.
Divall SA, Radovick S. Deciphering the genetics of stature-another piece of the puzzle. J Clin Endocrinol Metab. 91(4):1218-9, 2006.
Kim HH, Wolfe A, Cohen RN, Eames SC, Johnson AL, Wieland CN, Radovick S. In vivo identification of a 107-base pair promoter element mediating neuron-specific expression of mouse gonadotropin-releasing hormone. Mol Endocrinol. 21(2):457-71, 2007.
Naik K, Pittman I 4th, Wolfe A, Miller RS, Radovick S, Wondisford FE. A novel technique for temporally regulated cell type-specific Cre expression and recombination in the pituitary gonadotroph. J Mol Endocrinol. 37(1):63-9, 2007.
DiVall SA, Radovick S, Wolfe A. Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin. Mol Cell Endocrinol. 270(1-2):64-72, 2007.
Radovick S, DiVall S. Approach to the growth hormone-deficient child during transition to adulthood. J Clin Endocrinol Metab. 92(4):1195-200, 2007.
Miller R, Radovick S. Does treatment of childhood congenital adrenal hyperplasia with prednisone adversely affect final height? Nat Clin Pract Endocrinol Metab. 3(9):626-7, 2007.
Wolfe A, DiVall SA, Singh SP, Nikrodhanond AA, Baria AT, Le WW, Hoffman GE, Radovick S. Temporal and Saptial Regulation of CRE Recombinase Expression in Gonadotrophin-Releasing Hormone Neurons in the Mouse. J Neuroendocrinol. 20(7):909-16, 2008.
Wolfe A, Ng Y, DiVall SA, Singh SP, Radovick S. Development of an Immortalised, Post-Pubertal GnRH Neuronal Cell Line. J Neuroendocrinol, 20(9):1029-37, 2008.
Diaczok D, Romero C, Zunich J, Marshall I, Radovick S. A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency. J Clin Endocrinol Metab, 93(11):4351-9, 2008.
DiVall SA, Radovick S. Pubertal development and menarche. Ann N Y Acad Sci, 1135:19-28, 2008.
Chen, M. Wolfe, A, Wang, X, Chang, C., Yeh, S, Radovick, S. Generation and Characterization of a Complete Null ERα Mouse Using Cre/LoxP Technology. Mol Cell Biochem. Jan;321(1-2):145-53, 2009.
Chen, M., Hsu, I, Wolfe, A., Radovick, S., Lin, C-Y., Chang, Cl, Messing, E., Ye, S. Defects of Prostate Development and Reproductive System in the ERα Null Male Mice. Endocrinol Jan;150(1):251-9, 2009.
DiVall SA, Radovick S. Endocrinology of female puberty. Curr Opin Endocrinol Diabetes Obes. Feb;16(1):1-4, 2009.
Ng Y, Wolfe A, Novaira HJ, Radovick S. Estrogen Regulation of Gene Expression in GnRH Neurons. Ng and Wolfe contributed equally to this work, in press at Molecular and Cellular Endocrinology.
Singh SP, Wolfe A, DiVall SA, Radovick S. Conditional knock-out of the estrogen receptor alpha gene in the reproductive axis, in revision, Bio Reprod.
Novaira HJ, Ng Y, Wolfe A, Radovick S. Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines. Submitted.
Diaczok D, Mammen J, Novaira HJ, Kim HH, Wolfe A, Radovick S. Loss of Otx2 in GnRH neurons results in reproductive dysfunction. Submitted