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Most hormones have an ancient evolutionary history. The structures of many hormones are evolutionarily conserved. For example, some vertebrate hormones can also be found in many invertebrates. Since the first vertebrate animals diverged from invertebrates over 500 million years ago, some animal hormones are even older. In many cases, their roles in many invertebrate animals have yet to be discovered.

Typically, the same hormone serves different functions in vertebrates and in invertebrates, and may even serve different functions within distinct groups of vertebrates. Thyroid-stimulating hormone (TSH), a hormone released by the anterior pituitary gland that targets the thyroid gland, regulates metabolism in mammals but triggers metamorphosis in amphibians and feather molt in birds. It has even been found in snails and other invertebrates that lack a thyroid gland. Its function in snails appears to be stimulation of the number of sperm or eggs produced.

Recent genomic analysis has shown that the receptors for many hormones evolved well before the hormones with which they now interact. Even though the structure of a hormone or its receptor is often largely unchanged across diverse groups of organisms, hormones and their receptors can readily be selected to take on new roles as organisms evolve new behaviors and exploit new environments. An example is the shift in function of TSH to regulate metabolism in mammals and feather molt in birds from its role stimulating sperm or egg production in snails.

Another intriguing finding is that many peptides originally identified as hormones in various tissues have also been found to function as neurotransmitters in the nervous system. For example, oxytocin, which stimulates uterine contraction and the release of milk, also serves as a neurotransmitter in the brain and is believed to influence social behavior, as well as stimulate sexual arousal in mammals. Similarly, antidiuretic hormone, a peptide hormone that regulates water uptake in the kidneys (Chapter 41), also functions as a neurotransmitter in the brain influencing mammalian mating and pair-bonding behavior. Hence, the same compound, expressed in two different cell types, may have entirely different functions. The roles of hormones as chemical messengers are varied within an organism and easily changed over the course of evolution.