The strinking advances in peptide chemisry of recent years directed toward parathyroid hormone have resolved many of the basic chemical problems which originally hindered progress in this field. While continuing our basic chemical investigations to resolve critical aspects of structure/activity relations in hormone action which have led to the design and synthesis of several analogues of parathyroid hormone possessing diverse biological properties, we are now devoting increased attention to the mechanisms of hormone interaction with the target tissues and membrane receptors, steps subsequent to receptor binding, the metabolism of the hormones after their release from the sites of their syntheses, and the molecular biology of hormone biosynthesis. The ultimate goal of our unit is the systematic acquisition of sufficient information about hormonal function in mineral ion and bone metabolism, including the control of production and turnover of the hormones and an understanding of their complex and synergistic actions at the target tissues, to permit eventually precise and quantitative analyses of the normal patterns of control of calcium homeostasis and, thereby, to analyze more precisely the pathophysiology of disorders of calcium and bone metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK011794-24
Application #
3095125
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1979-01-01
Project End
1993-07-31
Budget Start
1991-08-17
Budget End
1992-07-31
Support Year
24
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Christov, Marta; Clark, Abbe R; Corbin, Braden et al. (2018) Inducible podocyte-specific deletion of CTCF drives progressive kidney disease and bone abnormalities. JCI Insight 3:
Dedic, Christopher; Hung, Tin Shing; Shipley, Alan M et al. (2018) Calcium fluxes at the bone/plasma interface: Acute effects of parathyroid hormone (PTH) and targeted deletion of PTH/PTH-related peptide (PTHrP) receptor in the osteocytes. Bone 116:135-143
Mizuhashi, Koji; Ono, Wanida; Matsushita, Yuki et al. (2018) Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 563:254-258
Hanna, Patrick; Grybek, Virginie; Perez de Nanclares, Guiomar et al. (2018) Genetic and Epigenetic Defects at the GNAS Locus Lead to Distinct Patterns of Skeletal Growth but Similar Early-Onset Obesity. J Bone Miner Res 33:1480-1488
Wein, Marc N; Foretz, Marc; Fisher, David E et al. (2018) Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential. Trends Endocrinol Metab 29:723-735
Bastepe, Murat (2018) GNAS mutations and heterotopic ossification. Bone 109:80-85
Roszko, Kelly L; Bi, Ruiye; Gorvin, Caroline M et al. (2017) Knockin mouse with mutant G?11 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors. JCI Insight 2:e91079
Grigelioniene, Giedre; Nevalainen, Pasi I; Reyes, Monica et al. (2017) A Large Inversion Involving GNAS Exon A/B and All Exons Encoding Gs? Is Associated With Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B). J Bone Miner Res 32:776-783
Balani, Deepak H; Ono, Noriaki; Kronenberg, Henry M (2017) Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest 127:3327-3338
Cheloha, Ross W; Chen, Bingming; Kumar, Niyanta N et al. (2017) Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad ? Residue Distribution. J Med Chem 60:8816-8833

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