++
A hormone is a molecule that is secreted into the circulation
to influence the function of target cells in another tissue or organ.
In addition to distant targets via the circulation (endocrine action), many
hormones also influence the function of the cells that secreted
them (autocrine action) or that of adjacent cells (paracrine action). For
example, when insulin, produced by pancreatic beta cells, stimulates
glucose storage and oxidation, protein synthesis, and lipid storage
in the liver, muscle and fat, it is acting in an endocrine fashion;
when it inhibits glucagon secretion by the nearby pancreatic alpha
cells, it is acting in a paracrine fashion. Frequently, the endocrine
and autocrine/paracrine actions of a hormone lead to the
same effect. For example, growth hormone (GH) stimulates hepatic
production of insulin-like growth factor I (IGF-I), the main mediator
of somatic growth in childhood. It has been shown that mice with
targeted deletion of IGF-I expression in only the liver grow to
normal size, despite a 75% reduction in their circulating
IGF-I concentration.1 This seminal experiment demonstrated
the importance of autocrine and paracrine IGF-I production to body
growth.
++
Hormone actions are mediated via systems with similar basic components.
This chapter will describe the specific components of the major categories
of hormones and will provide a methodological overview of how these
hormones contribute to health and disease. Each system is characterized
by the gland that produces a hormone, the hormone itself, and often
circulating binding proteins. The binding proteins create a circulating
pool of readily available hormone stores, alter hormone clearance
and distribution, and modulate hormone activity rates. Binding of the
free hormone, the ligand, to specific receptors on the target cells
initiates a variety of signal transduction pathways, often through
a series of signaling cascades or second messengers that alter cell
function. The impact of the hormonal message on cell function is
often modified by other regulatory molecules that modulate the activity
of these signaling pathways.
++
Hormones are categorized based on their molecular structure.
Most are peptide hormones, made of amino acid chains. Small neuropeptide
hormones include antidiuretic hormone (ADH), gonadotropin-releasing
hormone (GnRH), and thyrotropin-releasing hormone (TRH). Larger
peptide hormones, known as protein hormones, include
insulin and growth hormone (GH). Glycoprotein hormones have carbohydrate
side chains attached; these include human chorionic gonadotropin
(hCG), luteinizing hormone (LH), follicle-stimulating hormone (FSH),
and thyroid-stimulating hormone (TSH). Amino acid–derived
peptide hormones have an NH2 group at the end of the molecule
and arise from the amino acids tyrosine and tryptophan. These include
thyroxine, dopamine, catecholamines, and melatonin. In general,
peptide hormones work through cell surface receptors.
++
In contrast, steroid hormones are lipid and phospholipid derivatives.
These hormones are synthesized from cholesterol (eg, testosterone,
cortisol) or the eicosanoids (prostaglandins) by a series of enzymatic steps.
Other hormones are vitamin derivatives, including the retinoids
(vitamin A) and vitamin D. In general, thyroid hormones, steroid
hormones, retinoids, and vitamin D are lipid-soluble and work ...