Hormonal Signaling in Biology and Medicine

Comprehensive Modern Endocrinology

Gerald Litwack

• Publisher: Academic Press
• Year: 2019
• Print ISBN: 9780128138144
• eBook ISBN: 9780128138151
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Hormonal Signaling in Biology and Medicine: Comprehensive Modern Endocrinology covers the endocrine secretions produced by every organ. This extensive collection of knowledge is organized by tissue, addressing how certain hormones are synthesized in multiple tissues, along with their structure, function and pathways, which are very applicable for researchers in drug design who need to focus on a specific step along the pathway. This is a must have reference for researchers in endocrinology and practicing endocrinologists, but it is also ideal for biochemists, pharmacologists, biologists and students.- Serves as a valuable desk reference for researchers- Provides information on the structure of a given hormone, its receptor(s), and the pathways that become activated- Includes extensive citations to the literature that will enable the reader to dig more deeply into the effects of a given hormone

Chapter 1

Hormones and Perinatal Development

Max H. Cake ¹ , and George C.T. Yeoh ^{2 1} School of Veterinary and Life Sciences, Murdoch University, Perth, WA, Australia ² Harry Perkins Institute of Medical Research, QEII Medical Centre, Perth, WA, Australia

Abstract

The stimulatory or inhibitory effects of numerous hormones are required for many perinatal developmental events that are essential for postnatal survival. These developmental processes include the acquisition of gluconeogenesis, amino acid catabolism, and urea biosynthetic capacity in the neonatal liver; perinatal lung maturation; and alterations to digestive enzyme capabilities upon weaning. Much of our understanding of the mechanisms underlying regulation of the relevant biochemical pathways stems from the cloning of critical genes. Transcription factor motifs and enhancer sequences have been identified in their promoter regions, which are involved in regulating their expression and their perinatal appearance. Although enhanced expression of these genes, which leads to improved metabolic capacity and versatility of the tissues, is primarily the result of de novo transcription, there is compelling evidence that posttranscriptional mechanisms can also contribute.

Keywords

Androgens; Estrogens; Glucagon; Glucocorticoids; Hepatic; Insulin; Intestinal; Perinatal development; Respiratory

1. Introduction

Cell division is one of the most fundamental activities of multicellular existence. It is obviously important during embryological development, during which the single, fertilized ovum undergoes a complex, programmed sequence of cell divisions to generate a mature organism consisting of many millions of cells. Even after a higher animal has reached maturity, cell division is required to replenish those tissues that have suffered cell losses due to wear and tear. For instance, based on a blood volume of 4.7 L, human erythrocytes having a lifespan of 120 days and being present in blood at a concentration of 5 × 10¹² cells/L (Alberts et al., 2002), it was calculated that, just to maintain the erythrocyte population, an adult human must produce >2.3 million new erythrocytes per second, which confirms the value previously published (Sackmann, 1995). In this context, erythropoietin is the principal mediator that regulates the erythron (Adamson, 1996). There are a host of tissue-specific growth factors and hormones that determine the size of different organs of the body (Hafen and Stocker, 2003).

Numerous studies have shown, however, that hormones are essential for many eukaryotic developmental processes as well as for cellular homeostasis. Work from the laboratories of O'Malley (Tsai et al., 1978) and Chambon (Wasylyk et al., 1980; Chambon, 2004) showed that, through an interaction with specific receptor proteins, the hormone estrogen regulates the rate of expression of the genes for the egg white proteins, ovalbumin, conalbumin, ovomucoid, and lysozyme by interacting with and activating its cognate receptor so it binds to specific, upstream enhancer sequences. Subsequently, it has been shown that the majority of developmental events orchestrated by hormones are the result of transcriptional events initiated by interaction of specific nuclear regulatory proteins with transcriptional response sequences. This causes activation or inhibition of expression of specific genes, resulting in an altered level of the protein product. Although there are numerous examples that could be chosen to highlight the importance of hormones in activating specific developmental events, this chapter will focus on the postnatal development of key processes in the liver (gluconeogenesis, amino acid catabolism, and urea cycle function), the lung (surfactant production), and the intestine (digestion) of eukaryotes and especially address the impact of glucocorticoids, glucagon, epinephrine, and the inhibitory effects of insulin and androgens. The processes discussed are vital to postnatal survival, and if they are impaired, at a minimum, the health status of the postnatal organism is compromised.

2. Development of Hepatic Metabolic Processes

2.1. Neonatal Development of Hepatic Gluconeogenesis

The process of birth, upon completion of mammalian gestation, interrupts the continuous maternal supply of fuels that are provided via transplacental transfer, leading to an altered metabolic environment in the newborn. Although suckling provides an alternative fuel supply, there is a delay between birth and the onset of suckling. During this period, there is a reduction in the blood glucose concentration (hypoglycemia), which is quickly returned to normal levels as a result of phosphorylase activation (Dawkins, 1963; Cake and Oliver, 1969) that initiates glycogenolysis and the development of hepatic gluconeogenesis (Dawkins, 1963; Cake et al., 1971; Girard et al., 1973; Marsac et al., 1976).

In vertebrates, gluconeogenesis, which can be defined as the synthesis of glucose from noncarbohydrate precursors such as pyruvate, lactate, glycerol, and glycogenic amino acids, takes place mainly in the liver and in the cortex of the kidney (Gerich et al., 2001). Hepatic gluconeogenesis is virtually absent in the fetus and only becomes evident postnatally (Ballard and Oliver, 1963, 1965; Warnes et al., 1977; Platt and Deshpande, 2005). In rats, the inability to synthesize glucose from noncarbohydrate precursors prior to birth is due to the absence of the enzyme phosphoenolpyruvate carboxykinase (EC 4.1.1.32; PEP carboxykinase), despite the presence of the other three enzymes essential for gluconeogenesis, namely pyruvate carboxylase (EC 6.4.1.1), fructose 1,6-bisphosphatase (EC 3.1.3.11), and glucose 6-phosphatase (EC 3.1.3.9) (Ballard and Hanson, 1967; Yeung et al., 1967; Fig. 1.1). Natural birth or premature delivery by uterine section of fetal rats results in the appearance of PEP carboxykinase, which is linearly correlated with postnatal gluconeogenic activity (Yeung and Oliver, 1967). The appearance of the enzyme at this time is the result of a transcriptional event, which is apparent from the rapid accumulation of PEP carboxykinase mRNA from an undetectable level in the liver of the fetal rat late in gestation to a peak level 24 h after birth (Lyonnet et al., 1988).

The administration of the synthetic glucocorticoid, triamcinolone, does not precociously induce hepatic PEP carboxykinase activity in the fetal rat (Yeung et al., 1967; Mencher and Reshef, 1979). In contrast, in postnatal rats, which possess PEP carboxykinase activity, triamcinolone administration elicits a two- to threefold increase in enzyme activity. This increase was shown to be the result of increased synthesis of the enzyme, accompanied by enhanced PEP carboxykinase mRNA (Mencher and Reshef, 1979). Renal PEP carboxykinase, unlike that of the liver, was detectable prior to birth and was elevated in both fetal and postnatal animals when exposed to triamcinolone. Conflicting reports on the effect of glucocorticoids on PEP carboxykinase activity (Gunn et al., 1975; Mencher and Reshef, 1979) question the role played by glucocorticoids in the developmental regulation of this enzyme.

Figure 1.1 Developmental changes in the activities of the gluconeogenic enzymes pyruvate carboxylase (black), PEP carboxykinase (red), fructose 1,6-bisphosphatase (green), and glucose 6-phosphatase (blue) in the rat.
Data was taken from Yeung, D., Stanley, R.S., Oliver, I.T., 1967. Development of gluconeogenesis in neonatal rat liver. Effect of...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1. Hormones and Perinatal Development
• Chapter 2. Hormones of Programmed Cell Death
• Chapter 3. Hypothalamic Releasing Hormones
• Chapter 4. Neurosteroids: Biosynthesis, Molecular Mechanisms, and Neurophysiological Functions in the Human Brain
• Chapter 5. Neurotrophins and Neurotrophin Receptors
• Chapter 6. The Pineal as a Gland and Melatonin as a Hormone
• Chapter 7. Anterior Pituitary: Glycoprotein Hormones From Gonadotrope (FSH and LH) and Thyrotrope (TSH) Cells
• Chapter 8. Anterior Pituitary and Pars Intermedia Space: Corticotrophs (ACTH) and Melanotrophs (α-MSH)
• Chapter 9. Anterior Pituitary: Somatotrophs (GH) and Lactotrophs (PRL)
• Chapter 10. Posterior Pituitary Hormones
• Chapter 11. Hormones and the Regulation of Neuronal Voltage-Sensing Ion Channels
• Chapter 12. Hormonal Regulation of Epithelial Sodium Channel (ENaC) and Other Nonneuronal Epithelial Ion Channels
• Chapter 13. Thymosins
• Chapter 14. Heart Hormones
• Chapter 15. Stomach Hormones
• Chapter 16. Intestinal Hormones
• Chapter 17. Pancreatic Hormones
• Chapter 18. Liver Hormones
• Chapter 19. The Endocrine Kidney: Local and Systemic Actions of Renal Hormones
• Chapter 20. Adipocyte-Derived Hormones
• Chapter 21. Thyroid Hormones
• Chapter 22. Parathyroid Hormones
• Chapter 23. Hormones and Hormone Precursors of the Skin
• Chapter 24. Hormones of the Testes
• Chapter 25. Ovarian Hormones
• Chapter 26. Muscle Hormones
• Chapter 27. Hormones From Bone
• Chapter 28. Adrenal Cortex Hormones
• Chapter 29. Adrenal Medulla Hormones
• Chapter 30. Overproduction of Hormones by Pituitary Tumors
• Chapter 31. Hormone Effects on Tumors
• Index