The placental hormone human chorionic gonadotropin (CG) and the pituitary hormones lutropin (LH), follitropin (FSH) and thyrotropin (TSH) are a family of heterodimeric glycoproteins that share a common alpha subunit but differ in their hormone-specific subunits. One or more of these hormones is essential for gonadal development and maintaining pregnancy and thyroid function.
Our laboratory is focused on structure-function studies. Using site-directed mutagenesis, we are studying the structural determinants that govern the unique post-translational modifications of the related placental and pituitary glycoprotein hormones. These hormones undergo specific modifications and have unique biologic activities. Together with DNA-mediated transfection techniques, monoclonal antibody screening and protein and carbohydrate characterization, we can determine:
- The region in the hormone associated with unique biologic activity
- The region critical for subunit assembly; and
- Disulfide bonds for folding of these hormones and the sequences critical for the differential sorting of the pituitary hormones.
Studies are also underway to determine the ligand determinants which are critical for signal transduction in vivo, as well as dissecting the structure of the gonadal receptors associated with the biological action of these hormones. Such information has been useful for designing clinically useful agents for treating infertility. A major focus of the laboratory is elucidating the epitopes that govern the differential sorting of these hormones in unique pituitary secretion pathways.
St. Louis College of Pharmacy, St. Louis, MO B.S. 1964 Pharmacology
Purdue University, West Lafayette, IN M.S. 1966 Pharmacology
Washington University, St. Louis, MO Ph.D. 1970 Pharmacology
Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1981 – present
Associate Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1977 – 1981
Assistant Professor, Departments of Pharmacology and Obstetrics/Gynecology, Washington University School of Medicine, 1972 – 1977
Postdoctoral Fellow of the American Cancer Society in the laboratory of Dr. Philip
- Pearl, C., Jablonka-Shariff, A., and Boime, I. “Re-routing of an FSH analog to the regulated secretory pathway.” Endocrinology.” 151, 388-93 (2010).
- Pearl, C ,Boime, I. “Sulfation of LH does not affect intracellular trafficking.” Mol & Cell Endo. 309, 76-81 (2009).
- Jennings, M.W., Boime*, I., Daphna-Iken, D., Jablonka-Shariff, A., Conley, A.J., Colgin, M., Bidstrup, L.A., Meyers-Brown, G. A., Famula, T.R., Roser, J.F*. “The efficacy of recombinant equine follicle stimulating hormone (reFSH) to promote follicular growth in mares using a follicular suppression model.” Anim. Reprod. Sci. (2009). *Both laboratories contributed equally to this work.
- Fauser, B.C., Mannaerts, B.M., Devroey, P., Leader, A., Boime, I. and Baird, D.T. “Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency.” Hum. Reprod. Update. (2009).
- Jablonka-Shariff, A., Boime, I. “Secretory trafficking signal encoded in the carboxyl-terminal region of the CGβ subunit.” Molec. Endocrinol. (Baltimore, Md, 23, 316-23 (2009).
- Adams, T. E. and I. Boime. “The expanding role of recombinant gonadotropins in assisted reproduction.” Reprod Domest Anim 43 Suppl 2: 186-92 (2008).
- Jablonka-Shariff, A., Pearl, C.A., Comstock, A., Boime, I. “A Carboxyl-terminal Sequence in the Lutropin β subunit contributes to the sorting of Lutropin to the Regulated Pathway.” J. Biol. Chem, 283(17): 11485-11492 (2008).
- Lemke, E.P., Adams, B.M., Jablonka-Shariff, A., Boime, I., Adams, T.E. “Single-chain human gonadotropin analogs induce follicle development in sheep.” J. Endocrinol, 196, 593-600 (2008).
- 166. Yoon, M.J., Boime, I., Colgin, M., Niswender, K.D., King, S.S., Alvarenga, M., Jablonka-Shariff, A., Pearl, C. and Roser, J.F. “The efficacy of a single chain recombinant equine luteinizing hormone (reLH): Induction of ovulation, hormone profiles, and inter-ovulatory intervals.” Domestic Animal Endocrinol, 33, 470-9 (2007).
- 165. Antenos, M., Stemler, M., Boime, I., and Woodruff, T.K. “N-linked oligosaccharides direct the differential assembly and secretion of inhibin α- and βA-subunit dimers.” Molec. Endocrinol., 21, 1670-84 (2007).
- 164. Jablonka-Shariff, A., Roser, J.F., Bousfield, G.R., Wolfe, M.W., Sibley, L.E., Colgin, M., and Boime, I. “Expression and bioactivity of a single chain recombinant equine luteinizing hormone (reLH).” Theriogenology 67, 311-320 (2007).