Chapter 10

### INTRODUCTION

Enteric hormones orchestrate appetite, food-seeking behaviors, intake, physical and chemical digestion, and the absorption of the nutrients, intricately linking the brain, the intestines, and multiple endocrine organs to sustain the energy balance of an organism. In 1902, William Maddox Bayliss and Ernest Henry Starling demonstrated that the gastrointestinal (GI) system is the body’s largest endocrine organ. Their work with secretin establishes roles of the GI system beyond digestion and nutrition and includes systemic signaling between regions of the GI system and the central nervous system (CNS) to coordinate appetite, satiety, digestion, and absorption.

Work by John Sidney Edkins in 1902 led to discovery of “gastric secretin,” now known as gastrin. Secretin and gastrin were thought to be the primary chemical mediators of digestion until the 1920s, when cholecystokinin (CCK) was added to the list. Until the 1970s, these three mediators remained the central dogma of GI hormonal signaling. The 1970s, however, yielded an explosion in GI hormone research and the discovery of over 100 additional hormones. The GI system produces exclusively peptide hormones.

Enteric hormones are of great evolutionary importance. Many human enteric hormones can be isolated in similar forms from other species and arise from common precursor tissue-specific mechanisms, known as prohormone processing, yielding a variety of end products from a common precursor. These “alternative splicing” mechanisms create unique mediators with specific functions. Precursor hormones and their derivatives are referred to as a hormone family. These enteric hormone “families” include the gastrin, secretin, and somatostatin (SST) families, among others (Table 10-1). These examples represent conservation of precursors over centuries of species’ evolution. Despite the unique chemistry derived from the tissue-specific processing, similar signaling may occur at receptor sites within/between these families.

Table 10-1.   Enteric Hormone Families

In addition to roles in nutrient digestion, absorption, and satiety, many of the GI hormones, including CCK, gastrin, and glucagonlike-peptide (GLP-1), provide a “trophic” signal to organs of the GI system. This trophic effect helps maintain tissue in the GI tract; however, if pathologic concentrations are present, trophism can lead to overproduction of tissue, such as hypertrophied gastric mucosa in gastrinomas.

Enteric hormone regulation involves negative feedback loops, presence of products of digestion, direct hormonal signaling, and neurotransmission. One example of a negative feedback loop involves reduction of gastrin secretion in the stomach due to low pH encountered in the small intestine. Partially digested proteins yield polypeptides, which, when sensed in the small intestine, stimulate secretion of several hormones, including the incretins. Additional mechanisms for regulation of GI hormones include a hormonal “off” signal; for example, secretion of SRIH from the pancreas and other cells halts ...

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