Gastrointestinal Hormones
The scientific field of
endocrinology began with the discovery of secretin in 1904 by Starling. Since
then it has been shown that an incredibly diverse list of digestive tract
functions are influenced by a variety of gastrointestinal hormones. Specific functions
of gastrointestinal hormones and their respective disorders will be discussed
in greater detail in chapters on specific organs. A brief outline of major gut
hormones follows, as well as a tabulation of major digestive tract hormones.
The hormones of the gastrointestinal tract are released by three
mechanisms. Endocrine cells of the pancreas congregate in Langerhans islets
that are inter- mingled with groups of exocrine cells in the acini and in the
ducts. There they release a variety of hormones into the adjacent capillaries.
In contrast, most endocrine cells in the digestive system are unlike those in
other hormone-secreting organs of the endocrine system which are localized to
specific organelles in an organ or make up an entire gland. Enterochromaffin
cells containing peptide hormones and nonpeptide transmitters are interspersed
between other epithelial cells along the surface of the mucosa throughout the
stomach and intestines. The apical border of these specialized cells reaches
into the lumen, where microvilli can react to changes in the chemical
concentration of intraluminal contents. Gastrointestinal hormones are released
from these epithelial cells by three different modalities: (1) They may be
released into the local capillaries and thus into the systemic vascular system
in a typical endocrine fashion, as occurs in the pancreas; hormones released in
this endocrine fashion influence other digestive tract functions, the
blood flow, or the appetite in response to specific stimuli to the mucosa. (2) Other endocrine cells release their
hormones locally, through specific
organelles that release directly onto nearby cells in a paracrine fashion. (3)
Hormones may be released into the interstitial space in a less specific exocrine
manner. Through these highly specialized mechanisms, hormones are released
systemically, locally, or specifically onto nearby targeted cells.
Isolation, sequencing, and molecular analysis of intracellular messaging
systems that modify the release of gastrointestinal hormones have revealed just
how complex the regulation of these mediators are as they influence gut
function. A common feature of gastrointestinal hormones is the complex way in
which they are synthesized and processed post translationally. The hormones are typically derived from a large
pre translational messenger RNA that
may contain more than one hormone sequence. The translational products of these
mRNA messages are long peptide chains of prohormones or pre hormones. Post translationally they are cleaved into hormones of varying lengths,
each of which has a different affinity for its receptor ligand (e.g., gastrin
may circulate as big-gastrin 36, gastrin 34, or a smaller version of
gastrin-8).
Neuroendocrine cells can grow into tumors that may result in complex, often
characteristic clinical syndromes. These symptomatic neuroendocrine tumors may
occur sporadically or as part of the inherited syndrome multiple endocrine
neoplasia, which is due to a mutation of the MEN-1 gene which encodes a
cyclindependent kinase inhibitor. This autosomal dominant syndrome is
associated with tumors of the islet cells of the pancreas, parathyroid glands,
and pituitary gland. It may also be associated with tumors of the adrenal
cortex, carcinoid tumors, and nonendocrine tumors, including angiofibromas,
leiomyomas, collagenomas, lipomas, and meningiomas.
Increased understanding of gastrointestinal hormones has led to a variety
of diagnostic and therapeutic uses for them. One of the most valuable tools for
localizing and evaluating neuroendocrine tumors is a 111indium-labeled radioactive
modification of the somatostatin molecule in the “octreotide scan”
(somatostatin receptor scintigraphy). Modified somatostatin is also used to
treat upper gastrointestinal bleeding from esophageal
varices.
