Endocrine
Chapters
page 1 of 3 pages | next »Adaptation to Estradiol Deprivation Causes Up‑Regulation of Growth Factor Pathways and Hypersensitivity to Estradiol in Breast Cancer Cells
Richard J. Santen, Robert X. Song, Shigeru Masamura, Wei Yue, Ping Fan, Tetsuya Sogon, Shin-ichi Hayashi, Kei Nakachi and Hidtek Eguchi
Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regress...
Aromatase Expression in Women’s Cancers
Serdar E. Bulun and Evan R. Simpson
Estrogen has been positively linked to the pathogenesis and growth of three common women’s cancers (breast, endometrium and ovary). A single gene encodes the key enzyme for estrogen biosynthesis named aromatase, inhibition of which effectively eliminates estrogen production in the entire body. Aroma...
b Cell Proliferation as the Major Determinant of Pancreatic b Cell Mass
Zvi Granot and Yuval Dor
A fundamental problem in pancreas biology concerns the cellular origins of adult pancreatic b cells. Identifying the cells that give rise to new b cells will have important implications for the design of future regenerative therapies for diabetes. Numerous studies have suggested that b cells...
Breast Development, Hormones and Cancer
Jose Russo and Irma Russo
Breast cancer originates in undifferentiated terminal structures of the mammary gland. The terminal ducts of the Lob 1 of the human female breast, which are the sites of origin of ductal carcinomas, are at their peak of cell replication during early adulthood, a period during which the breast is mor...
Cell Cycle Machinery: Links with Genesis and Treatment of Breast Cancer
Alison J. Butt, C. Elizabeth Caldon, Catriona M. McNeil, Alexander Swarbrick, Elizabeth A. Musgrove and Robert L. Sutherland
Loss of normal growth control is a hallmark of cancer. Thus, understanding the mechanisms of tissue‑specific, normal growth regulation and the changes that occur during tumorigenesis may provide insights of both diagnostic and therapeutic importance. Control of cell proliferation in the normal...
Cell Cycle Regulation and Beta Cells
Senta Georgia and Anil Bhushan
Cells regulate proliferation by entering and progressing through the cell cycle. Conversely, cell growth is arrested by exiting the cell cycle. A balance of extrinsic and intrinsic signals normally mediates progression through or exit from the cell cycle.1 When mitotic signals are received b...
Central Regulation of Insulin Sensitivity
Silvana Obici and Luciano Rossetti
Insulin rapidly lowers blood glucose levels via inhibition of endogenous glucose production and stimulation of glucose uptake. The mechanisms by which insulin modulates hepatic glucose production involve either activation of insulin signaling in hepatocytes (direct effects) or activation of insulin ...
Control of Protein Synthesis by Insulin
Joseph F. Christian and John C. Lawrence, Jr.
The stimulation of protein synthesis is a classic action of insulin. Loss of the stimulatory effect of insulin on protein synthesis contributes to the cessation of growth and weight loss, which are hallmarks of untreated Type 1 diabetes mellitus. The effect of insulin on protein metabolism is comple...
Development of Parathyroid Glands
Thomas Gunther and Gerard Karsenty
The parathyroid glands (PG) are the main source for circulating parathyroid hormone (PTH), a hormone that is essential for the regulation of calcium and phosphate metabolism. The PGs develop during embryogenesis from the pharyngeal pouches with contributions from endodermal and neural crest cells...
Diverse Signalling Mechanisms Used by Relaxin in Natural Cells and Tissues: The Evolution of a “Neohormone”
Richard Ivell, Kee Heng and Ravinder Anand-Ivell
The small peptide hormone relaxin is a member of a rapidly evolving family of hormones and growth factors, whose mode of action appears to be particularly adapted to purely mammalian physiology. It is representative of a new category of hormones, referred to as neohormones, which appear to have evol...
Endogenous Hormone Levels and Risk of Breast, Endometrial and Ovarian Cancer: Prospective Studies
A. Heather Eliassen and Susan E. Hankinson
Multiple lines of evidence support a central role of hormones in the etiology of breast, endometrial and ovarian cancers. Evidence of an association between circulating hormones and these cancers varies by both hormone and cancer site, with the most consistent associations observed for sex steroid h...
Epidemiology of Hormone‑Associated Cancers as a Reflection of Age
Svetlana V. Ukraintseva, Konstantin G. Arbeev and Anatoli I. Yashin
In this chapter we review the epidemiology of hormone‑associated cancers (prostate, breast, endometrial, ovarian, pancreatic and thyroid) paying special attention to the variability in the age patterns of cancer incidence rate over populations and time periods. We emphasize the comparative ana...
Genetic Causes of Hypoparathyroidism
Rachel I. Gafni and Michael A. Levine
Hypoparathyroidism is characterized clinically by the presence of hypocalcemia and hyperphosphatemia due to inadequate supply or effectiveness of circulating parathyroid hormone (PTH). It may be present either as an isolated finding or as a component of a more complex developmental, metabolic, or...
Hepatic Regulation of Fuel Metabolism
Catherine Clark and Christopher B. Newgard
It has been recognized for more than a century that the liver plays an important role in maintaining metabolic fuel homeostasis. The purpose of this chapter is to summarize mechanisms by which circulating glucose and lipid concentrations are controlled by hepatic metabolic activities. Glucose metabo...
Hepatocyte Growth Factor (HGF) and the Pancreatic Beta Cell
Jose A. Gonzalez-Pertusa, Laura Alonso and Adolfo Garcia-Ocaña
Studies performed in vivo using genetically modified mouse models have shown that growth factors are regulators of beta cell growth and differentiation. Hepatocyte growth factor (HGF), initially identified as a circulating factor implicated in hepatic regeneration, displays pleiotropic actions...
Hormonal Heterogeneity of Endometrial Cancer
Carsten Gründker, Andreas R. Günthert and Günter Emons
Endometrial cancer is the most common malignant tumor of the female genital tract in the developed world. Increasing evidence suggests that the majority of cases can be divided into two different types of endometrial cancer based on clinico‑pathological and molecular characteristics. Type I is...
How Might PTHs Stimulate Bone Growth?
James F. Whitfield
To tackle the formidable job of understanding how the PTHs stimulate bone growth in humans, rodents and other animals (Fig. 17) we must know where and how things start. What signals do they send into their target cells via the PTHR1 receptors to trigger osteogenesis? However, before going on I must...
In Silico Analysis of Regulatory Sequences in the Human Parathyroid Hormone Gene
Alexander Kel, Maurice Scheer and Hubert Mayer
Parathyroid hormone (PTH) is intimately involved in the homeostasis of normal serum concentrations of calcium and phosphate, which, in turn, regulate the synthesis and secretion of PTH. The synthesis and secretion of PTH in the parathyroid gland is regulated at the transcriptional, posttranscript...
Insulin Action Gene Regulation
Calum Sutherland, Richard M. O'Brien and Daryl K. Granner
Insulin regulates metabolism by altering the concentration of critical proteins or by inducing post-translational modifications of preexisting molecules. The latter represents a well-recognized action of insulin, and it has been extensively studied for many years. By contrast, it is only recently th...
Insulin Action in the Islet b-Cell
Rohit N. Kulkarni
The techniques that allow spatio-temporal control of gene deletion or gene expression in transgenic and knockout animals have been useful to directly evaluate the roles of the insulin and IGF-1 receptors and proteins in their signaling pathway in islet cells. While a functional role for insulin sign...
Insulin and IGF-I Receptor Structure and Binding Mechanism
Pierre De Meyts, Waseem Sajid, Jane Palsgaard, Anne-Mette Theede, Lisbeth Gauguin, Hassan Aladdin, Jonathan Whittaker and Jonathan Whittaker
The insulin and IGF-I receptors are members of the superfamily of receptor tyrosine kinases (RTKs). Unlike most RTKs that are single-chain monomeric transmembrane polypeptides, the insulin and IGF-I receptors are covalent dimers composed of two extracellular £ subunits and two transmembrane £] subun...
Insulin Resistance
C. Hamish Courtney and Jerrold M. Olefsky
Insulin resistance can be said to exist “whenever normal concentrations of hormone produce a less than normal biological response”. In the 1930s, Himsworth first differentiated patients with diabetes mellitus into “insulin sensitive” and “insulin insensitive” based on the ability of subcutaneous ins...
Mechanisms of Hormone Carcinogenesis: Evolution of Views, Role of Mitochondria
Jin-Qiang Chen, Terry R. Brown and James D. Yager
Cumulative and excessive exposure to estrogens is associated with increased breast cancer risk. The traditional mechanism explaining this association is that estrogens affect the rate of cell division and apoptosis and thus manifest their effect on the risk of breast cancer by affecting the growth o...
Menopause and Bone Loss
James F. Whitfield
So far it has seemed that estrogen is the primus inter pares of an ever-growing number of agents that control bone growth and strength in both women and, perhaps surprisingly, men (Baylink et al, 1999; Klein, 1999; Stevenson and Lindsay, 1999; Vanderschueren et al., 2000). Now it appears that bones ...
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