Endocrine
Chapters
« previous | page 3 of 3 pagesSkeletal and Reproductive Abnormalities in Pth-Null Mice
Dengshun Miao, Bin He, Beate Lanske, Xiu-Ying Bai, Xin-Kang Tong, Geoffrey N. Hendy, David Goltzman and Andrew C. Karaplis
We have examined the role of parathyroid hormone (PTH) in the postnatal state in a mouse model of PTH-deficiency generated by targeting the Pth gene in ES cells. Mice homozygous for the ablated allele, when maintained on a normal calcium intake, developed hypocalcemia, hyperphosphatemia, and low ...
Strontium, Calcium’s Big Brother
James F. Whitfield
Strontium (Sr) has been very recently hyped as the latest “paradigm-changing” thing in the treatmen of osteoporosis as indicated by the title of a paper by Reginster et al (2003)—“Strontium Ranelate: A New paradigm for the treatment of Osteoporosis”. When two atoms of strontium combine with ranelic ...
Subcellular Compartmentalization of Insulin Signaling Processes and GLUT4 Trafficking Events
Robert T. Watson, Alan R. Saltiel, Jeffrey E. Pessin and Makoto Kanzaki
Skeletal muscle and adipose tissue are the major sites of postprandial glucose disposal. The insulin-regulated transport of glucose into these tissues is a multi-step process that begins with the binding of insulin to its cell surface receptor. Once activated, the insulin receptor generates multiple...
Surface Signaling Steroids—Real Anabolics or Pseudo-Anabolics?
James F. Whitfield
In 1998 Sicinski et al reported the synthesis of new 1a, 25-(OH)2-19-nor-vitamin D3 analogs such as 2MD (2-methylene-19-nor-(20S)-1a,25(OH)2D3) which are super-potent derivatives of the natural 1a, 25-(OH)2-vitamin D3. Four years later Shevde et al. (2002) reported that 2MD is a far more potent stim...
The Amazing Bone-Anabolic PTHs
James F. Whitfield
Clearly the antiresorptives are far from being the ‘Holy Grails’ of osteoporosis therapy although they do break the vicious cyle of escalating remodeling and microdamage (Fig. 10). Since by the time of their first fracture, the bones of osteoporotic postmenopausal women have undergone considerable m...
The Calcium Sensing Receptor
Shozo Yano and Edward M. Brown
The acute secretory response of parathyroid hormone (PTH) is strictly regulated by the extracellular calcium concentration (Ca2+ o), and the G protein-coupled, calcium-sensing receptor (CaR) located on the chief cells of the parathyroid glands mediates this process. Abnormalities of the Ca2+ o-...
The Clinical Prospects of the Invincible PTHs
James F. Whitfield
The osteoporosis market is a rapidly growing “marketer’s” dream. And several years ago there was no known bone-growing drug—only the ever-worrisome (for cancerophobics) estrogens and the other antiresorptives. So the marketeers at Eli Lilly decided that the old hPTH-(1-34) would be the ideal drug wi...
The Effects of Relaxin on Extracellular Matrix Remodeling in Health and Fibrotic Disease
Chrishan S. Samuel, Edna D. Lekgabe and Ishanee Mookerjee
Since its discovery as a reproductive hormone 80 years ago, relaxin has been implicated in a number of pregnancy‑related functions involving extracellular matrix (ECM) turnover and collagen degradation. It is now becoming evident that relaxin’s ability to reduce matrix synthesis and increase E...
The Evolution of the Relaxin Peptide Family and Their Receptors
Tracey N. Wilkinson and Ross A.D. Bathgate
The relaxin peptide family in humans consists of relaxin‑1, 2 and 3 and the insulin‑like peptides (INSL)‑3, 4, 5 and 6. The evolution of this family has been controversial; points of contention include the existence of an invertebrate relaxin and the absence of a ruminant relaxin. ...
The Statins
James F. Whitfield
While the PTHs are by far the leading anabolic agents for treating osteoporosis and mending fractures, another family of drugs has been trying to challenge them but with very mixed results (Mundy, 2000; Whitfield, 2001, 2002a). These now old drugs were discovered by Endo and colleagues during a sear...
The Treatment of Neuroendocrine Tumors (NET) with Somatostatin Analogs
Beata Kos-Kudla
There is increasing interest in somatostatin (SST) analogs in the diagnosis and therapy of neuroendocrine tumors (NET), which constitute a heterogeneous group of neoplasms often associated with typical symptoms due to excessive production of hormones and bioactive substances. SST analogs have ...
The Vascular Actions of Relaxin
Arundhathi Jeyabalan, Sanjeev G. Shroff, Jaqueline Novak and Kirk P. Conrad
Relaxin is emerging as a hormone with important vascular actions. Much of our recently gained knowledge of relaxin in this context has stemmed from investigations of maternal vascular adaptations to pregnancy in which the hormone is turning out to be an important mediator. This chapter is separated ...
Toward an Understanding of Human Parathyroid Hormone Structure and Function
Lei Jin, Armen H. Tashjian, Jr., and Faming Zhang
Parathyroid hormone (PTH) is synthesized as a 115 amino acid precursor and secreted as an 84 amino acid polypeptide that regulates extracellular calcium homeostasis via actions directly on kidney and bone and indirectly on the intestine by facilitating calcium absorption.1 PTH and a related molec...
Transgenic Models of Impaired Insulin Signaling
Francesco Oriente and D Accili
Insulin resistance plays a key role in the pathogenesis of several human diseases, including diabetes, obesity, hypertension and cardiovascular diseases. The predisposition to insulin resistance results from genetic and environmental factors. The search for gene variants that predispose to insulin r...
Vitamin D Analogs for the Treatment of Secondary Hyperparathyroidism in Chronic Renal Failure
Alex J. Brown
Secondary hyperparathyroidism (2oHPT) is a common complication in patients with chronic renal failure. The pathogenesis of 2oHPT is attributed primarily to phosphate retention and low serum 1,25(OH)2D3. Replacement therapy with calcitriol [1,25-dihydroxyvitamin D3 or 1,25(OH)2D3] or its precursor...
What Is Osteoporosis?
James F. Whitfield
Osteoporotic postmenopausal women don’t need to fall or hit something to break their fragile bones. Their, hips, ribs, wrists and especially vertebrae are apt to be broken or crushed by bending spines, muscle pullings and the low-impact bumps of ordinary daily activities. In fact the greatest bone b...
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